**Assessment of Bovine Spongiform Encephalopathy (BSE) risks associated
with the importation of certain commodities from BSE minimal risk
regions (Canada)**

> Veterinary Services

Animal and Plant Health Inspection Service

> United States Department of Agriculture
>
> October 27, 2006

**Table of Contents**

+--------------------------------------------------------------+-------+
| List of Tables and Figures                                   | 6     |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| Executive Summary                                            | 7     |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| I. *Introduction*                                            | 10    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| II\. *Hazard Identification*                                 | 13    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > A. Transmission                                            | 14    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > B. Incubation                                              | 17    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > C. Tissue distribution and infectivity                     | 18    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| III\. *Release Assessment*                                   | 20    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > A. Estimation of BSE prevalence in Canada                  | 20    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 1\. BSurvE Model                                           | 21    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 2\. Bayesian Birth Cohort Model (BBC): Inclusion of feed   | 22    |
| > ban data                                                   |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 3\. Summary of assumptions and methods used in the         | 23    |
| > Canadian calculations                                      |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 4\. Results of prevalence estimation                       | 25    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > a\. Application of Prevalence Estimates to the Exposure    | 25    |
| > Assessment                                                 |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > B. Release of infectivity via the various commodities      | 26    |
| > proposed for importation                                   |       |
|                                                              |       |
| from Minimal Risk Regions                                    |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 1\. Release of BSE infectivity via live bovines            | 26    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > a\. Feed ban in Canada                                     | 27    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 1\. Implementation of the feed ban                         | 28    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 2\. Rendering industry                                     | 30    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 3\. Addressing cross-contamination                         | 30    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 4\. Education and industry awareness                       | 31    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 5\. Inspections and compliance                             | 32    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 6\. On-farm feeding practices contributing to feed ban     | 32    |
| > efficacy                                                   |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > b\. Conclusions: Infectivity release via importation of    | 33    |
| > live bovines                                               |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 2\. Release of BSE infectivity via blood and blood         | 33    |
| > products                                                   |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > a\. Scope of the analysis: relevant products               | 34    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > b\. Infectivity of blood and the relevant blood products   | 35    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > c\. Likelihood of maternal transmission of BSE             | 36    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > d\. Proposed mitigations to prevent contamination at       | 37    |
| > collection                                                 |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 3\. Release of BSE via small intestine other than distal   | 37    |
| > ileum                                                      |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > a\. Infectivity of the small intestine                     | 38    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > b\. Likelihood of improper removal of the distal ileum     | 39    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 1\. Relevant anatomy of bovine small intestine             | 39    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 2\. Mitigations to exclude distal ileum from imported      | 39    |
| > small intestine                                            |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > c\. Conclusions: Infectivity release via importation of    | 40    |
| > bovine intestines                                          |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > C. Projections and composition of cattle imports from      | 40    |
| > Canada under the proposed rule                             |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 1\. Slaughter cattle                                       | 41    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 2\. Feeders/stockers                                       | 42    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 3\. Breeding cattle                                        | 42    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 4\. Projected bison imports                                | 44    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > D. Release conclusions                                     | 44    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 1\. Likelihood of BSE release via import of live bovines   | 45    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > a\. Release of BSE infectivity via import of live bison    | 47    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 2\. Release of BSE infectivity via import of blood and     | 48    |
| > blood products                                             |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > a\. Likelihood of cross-contamination at slaughter         | 48    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 3\. Release of BSE infectivity via import of small         | 49    |
| > intestines other than distal                               |       |
| >                                                            |       |
| > ileum                                                      |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 4\. Release conclusions                                    | 50    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| IV\. *Exposure Assessment*                                   | 50    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > A. Live Bovines                                            | 50    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 1\. Pathway analysis: Barriers to BSE transmission and     | 50    |
| > amplification                                              |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 2\. Quantitative evaluation of BSE exposure and spread in  | 52    |
| > the United States                                          |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > a\. Methodology                                            | 52    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 1\. Current (2006) updates to the BSE Exposure Model and   | 53    |
| > input parameters                                           |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 2\. Significant and/or updated (2005-2006) parameters      | 54    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > \(a\) Import of infected cattle                            | 54    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > \(b\) Slaughter process                                    | 55    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > \(c\) Proportion of animals that are rendered              | 55    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > \(d\) Rendering process                                    | 56    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > \(i\) Inactivation during rendering                        | 56    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > \(ii\) Cross-contamination and mislabeling at rendering    | 57    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > \(e\) Disposition of meat and bone meal                    | 58    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > \(f\) Feed manufacturing process                           | 59    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > \(g\) On-farm misfeeding                                   | 59    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > \(h\) Poultry litter exposure pathway                      | 60    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 3\. Sensitivity analysis                                   | 60    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > b\. Results                                                | 61    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 1\. Base case results                                      | 61    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 2\. Sensitivity analysis results                           | 62    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 3\. Live animal qualitative exposure assessment            | 62    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 4\. Live animal exposure summary                           | 63    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > B. Qualitative exposure assessment for blood and blood     | 63    |
| > products imported from                                     |       |
| >                                                            |       |
| > Canada                                                     |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 1\. Risk mitigation by processing of FBS and other blood   | 64    |
| > products                                                   |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > 2\. FBS and blood product use in veterinary vaccine and    | 65    |
| > drug manufacture                                           |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > C. Qualitative analysis for exposure resulting from the    | 66    |
| > importation of small                                       |       |
| >                                                            |       |
| > intestine other than the distal ileum                      |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| V. *Consequence Assessment*                                  | 67    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| VI\. *Risk Estimation*                                       | 68    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > A. Live bovines                                            | 69    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > B. Blood and blood products                                | 70    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > C. Bovine small intestine other than the distal ileum      | 71    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| > D. Conclusion of risk estimation for all commodity groups  | 71    |
| > considered                                                 |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| References                                                   | 72    |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| Attachment 1: Estimation of BSE Prevalence in Canada         |       |
+--------------------------------------------------------------+-------+
|                                                              |       |
+--------------------------------------------------------------+-------+
| Attachment 2: Harvard Model of Bovine Spongiform             |       |
| Encephalopathy Implications of Importing Cattle Over 30      |       |
| Months of Age from Canada                                    |       |
+--------------------------------------------------------------+-------+

**List of Tables and Figures**

**Table 1 --** Confirmed Cases in Great Britain by year of birth, where
known

**Table 2** -- Infectivity in a clinical case of BSE (cattle oral
ID~50~)

**Table 3** -- Results of prevalence calculation

**Table 4** -- Projected percentages of cattle imports from Canada with
the proposed rule

**Table 5** -- Projected imports of various cattle use types for years
2007 through 2026

**Table 6** -- Projected bison imports

**Table 7** -- Projected percentages, total (number), and infected
cattle imports by usage

type from Canada for 2007

**Table 8** -- Differences in the parameter regarding the disposition of
MBM used for the

Cohen, et al. 2001/2003 and Cohen 2005/2006 Risk Assessments

**Figure 1** -- Effect of the feed ban on BSE cases in Great Britain

**Executive Summary**

On January 4, 2005, the U.S. Department of Agriculture's (USDA) Animal
and Plant Health Inspection Service (APHIS) published in the *Federal
Register* a final rule (70 FR, Docket No. 03-080-3, pages 459-553) to
amend the regulations regarding the importation of animals and animal
products to 1) establish a category of regions that present a minimal
risk of introducing bovine spongiform encephalopathy (BSE) into the
United States (BSE minimal risk regions) via live ruminants and ruminant
products and byproducts, and 2) add Canada to that category. That rule
also established conditions for the importation of certain live
ruminants and ruminant products and byproducts from such regions.

We are now proposing to amend the regulations to allow the importation
of certain additional commodities from BSE minimal risk regions --
currently, only Canada. This risk assessment evaluates the potential BSE
risk associated with the proposed regulations. The risk assessment
indicates that the proposed actions will continue to protect against the
introduction and establishment of BSE into the United States.

Commodities discussed in this risk analysis reflect those that, in
accordance with the World Organization for Animal Health (OIE)
guidelines, can be safely traded under certain conditions. APHIS is
considering allowing the importation of 1) live bovines (cattle and
bison) that were born after the date when a ruminant-to-ruminant feed
ban was effectively enforced; 2) blood and blood products collected
under certain conditions; and 3) bovine small intestine, other than
distal ileum, under certain conditions.

This risk assessment includes both quantitative and qualitative
evaluations of the animal health risks associated with these products
and the likelihood that these products imported from minimal risk
regions (Canada) would introduce BSE infectivity into the United States
and expose the U.S. cattle population. The analysis uses the approach
recommended by the OIE (*Terrestrial Animal Health Code* Section 1.3
Risk Analysis) for trade-related animal health risk assessments, which
focuses on determining likelihood of release (i.e., introduction of the
disease agent), likelihood of exposing susceptible animals given
release, and the magnitude of consequences given release and exposure.

The analysis includes consideration of the effects of proposed
mitigations for each of these commodities as follows:

1.  Live cattle and bison: live bovines were born on or after March 1,
    1999.

2.  Blood and blood products:

> For all blood:

a.  the blood is collected in a closed system.

> For blood collected at slaughter:

b.  the slaughtered animal passed ante-mortem inspection and

c.  was not subjected to a stunning process with a device injecting
    compressed air or gas into the cranial cavity or a pithing process.

> For fetal bovine serum:

d.  the dam passed ante-mortem inspection and was not subjected to a
    stunning process with a device injecting compressed air or gas into
    the cranial cavity or a pithing process.

e.  the uterus is removed from the dam's abdominal cavity intact and
    taken to a separate area away from the kill floor.

> For blood collected from live donors:

f.  the donor must be free of clinical signs of disease.

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3.  Bovine small intestine: small intestine must exclude the distal
    ileum by removing at least 80 inches of the uncoiled and trimmed
    small intestine as measured from the cecocolic junction and
    progressing proximally toward the jejunum.

The analysis uses both qualitative and quantitative methods for various
parts of the assessment. As part of the release assessment, we use
quantitative methods to estimate the current prevalence of BSE in the
standing adult cattle population in Canada. We use qualitative methods
to describe the most likely outcomes of the release assessment. In the
exposure assessment, we again combine both qualitative and quantitative
methods. In those instances where we either cannot numerically represent
the expected outcome, or where the numbers would be so low as to prevent
their use in further calculations, we qualitatively assess the possible
exposure. To conduct a quantitative assessment of the possible exposure
we make assumptions expected to overestimate the overall risk in order
to provide sufficient numeric input for the model.

The BSurvE model with modifications is used to quantitatively estimate
the prevalence of BSE in the standing adult cattle population of Canada.
As this model cannot predict future changes in prevalence, we
qualitatively evaluate the available evidence to anticipate how the
prevalence may change. Based on evidence from the United Kingdom (UK)
and Europe about the effects of a feed ban, as well as on the results of
simulation models, we expect that the prevalence of BSE in Canada will
decrease continuously over the next several years. A key assumption
underlying this expectation is that an effectively implemented feed ban
will be sufficient to eventually eradicate BSE in a country's cattle
population. Although the BSE epidemic curve in Europe exhibits a long
tail, the assumption of eventual eradication of the disease resulting
from a feed ban is consistent with epidemiologic simulation modeling
predictions.

Although this scenario is the most likely, because we cannot provide an
accurate prediction for the rate at which we might expect the already
low prevalence to decrease, we cannot numerically represent the expected
annual release over the time period of the analysis. Therefore this
scenario is described qualitatively.

We quantitatively evaluated other less likely scenarios expected to
over-estimate the overall risk. For this assessment, we assume that the
August 2006 prevalence, calculated using the Bayesian Birth Cohort (BBC)
model, remains constant over the next 20 years. Even if the BBC model
were to slightly underestimate the current prevalence of BSE in Canada
(an alternative current prevalence estimate is provided for sensitivity
analysis), we expect that assuming it to remain constant at this level
over the next 20 years would overstate prevalence during the time
horizon of the analysis. This assumption of constant prevalence,
combined with the estimates of projected cattle imports from Canada,
provide the values for release of infected live animals in this less
likely scenario. This numeric input is necessary for the quantitative
model used to inform the exposure assessment.

The exposure assessment for live animals qualitatively indicates that,
because the most likely expectation is that Canada's prevalence will
decrease over time, and because of the barriers to BSE transmission in
the United States, that the likelihood of BSE exposure and establishment
in the U.S. cattle population as a consequence of infectivity introduced
via imports from Canada is negligible. In our quantitative consideration
of less likely scenarios, the exposure assessment evaluates the impact
of the numbers of infected animals imported, assuming constant BSE
prevalence in Canada, on the likelihood of U.S. cattle exposure to BSE.
We base our evaluation on the Harvard Center for Risk Analysis BSE
simulation by Cohen et al., updated to incorporate new evidence and
domestic regulations, and the proposed changes considered here. In order
to provide time for several potential infectivity cycles, this model
tracks BSE release and exposure in the United States over 20 years. In
the current analysis, it indicates that even with risk-inflating
assumptions about the possible level of infectivity released into the
United States, there is little spread of disease to U.S. animals.
Assuming the less likely scenario of constant BSE prevalence in Canada,
the model predicts that over the 20 years of the analysis, importation
of approximately 19 infected animals leads to approximately two U.S.
cases as secondary spread. Since most animals are slaughtered during the
lengthy incubation period, only 0.67 of all 21 infected animals
predicted by the model would live to show clinical signs.

Considering evidence provided in the consequence assessment, we expect
that even the unlikely scenario evaluated in the quantitative release
and exposure assessments results in negligible economic costs of BSE.
Although human health is not the focus of this assessment, we note that
the quantitative model, which includes multiple sources of risk
over-estimation, indicates a negligible level of infectious agent that
may be potentially available for human exposure. We conclude that the
consequences and resulting risk of importation of live bovines under the
conditions specified are negligible.

The risk of release and exposure via blood and blood products, and
bovine small intestine other than distal ileum, were evaluated
qualitatively. We conclude that the joint likelihood of BSE release and
subsequent exposure of bovines to infectivity from either of these
commodities is negligible. We further conclude that this negligible
likelihood would result in extremely few or no U.S. cases of BSE.
Therefore, the consequences and resulting risk of the importation of
these commodities are negligible.

I.  **Introduction**

*The Bovine Spongiform Encephalopathy Minimal Risk Regions (BSE MRR)
rule:* The BSE MRR rule (APHIS 2005) established the criteria for a BSE
minimal risk region, determined that Canada met those criteria, and
specified the commodities permitted import under the regulation. We are
not proposing to amend either the criteria for a BSE minimal risk
region, or the designation of Canada as meeting those criteria in this
rule. We are, however, proposing to amend the commodities permitted for
import under the MRR designation.

The following summarizes those aspects of the rule that are relevant to
the current proposal:

The criteria for minimal risk regions ensure that such regions have
taken appropriate control measures to maintain a low prevalence of BSE
and conduct surveillance in accordance with international guidelines to
monitor the presence of disease. Existing regulations allow the
importation, under certain conditions, of live ruminants and certain
ruminant products and byproducts. Previous risk assessments concluded
that live bovines could be safely imported as long as they were
slaughtered before they were 30 months of age. To ensure slaughter by
this age limit, regulations were established concerning identification,
controlled movements, and monitoring. These assessments also concluded
that bovine meat and meat products could also be imported under certain
conditions.

Both the United States and Canada have conducted extensive surveillance
programs since the middle of 2004. Since January 4, 2005, when the final
rule recognizing Canada as a minimal risk region was published, seven
cases of BSE have been identified in Canada. In the United States, two
indigenous cases of BSE have been identified - one in July 2005 and one
in March 2006. The additional information obtained from these
surveillance efforts and additional epidemiological analysis of all of
the BSE cases support the substantive analysis outlined in this
document. This analysis supports the proposed changes to allow the
import of certain additional live bovines, certain bovine blood and
blood products, and bovine intestines, other than the distal ileum.

*Scope*

USDA APHIS' regulatory authority under the Animal Health Protection Act
covers factors impacting the health of livestock. Therefore, the scope
of this risk assessment is limited to animal (specifically, bovine
livestock) health pathways and consequences. Other potential impacts on
aspects of the "human environment,[^1]" including public health, are
addressed to comply with the National Environmental Protection Act
(NEPA) in the accompanying environmental assessment (APHIS 2006).

To facilitate the quantitative analysis of the likelihood of
introduction and spread of BSE via imports of live bovines, we use a
screening approach which includes all bovines that would be allowed
entry under the proposed regulation. Thus, the analysis is not
incremental in that we include animals that are already allowed entry
under current regulations. We recognize that by including in the
analysis animals that are already allowed entry (for slaughter by 30
months of age) we are increasing the estimated likelihood of introducing
infected animals beyond that which may result from the proposed imports
alone. If the risk associated with the entire group analyzed is
acceptable then no further analysis is necessary. However, the analysis
is not cumulative in that we do not consider the level of indigenous
infectivity that may currently be present in the U.S. cattle population.

*Format*

The format of this risk assessment follows OIE guidelines. The risk
assessment proper is preceded by a Hazard Identification section in
which we specify for what pest or disease of livestock we are assessing
the risk. In this case, we are restricting the assessment to BSE that
may be introduced in live animals and certain bovine-derived products
from Canada, a BSE minimal risk region. The risk assessment itself
includes the four sections specified by the OIE's *Terrestrial Animal
Health Code* Section 1.3 Risk Analysis (OIE 2006b). The Release
Assessment evaluates the likelihood that animals or products proposed
for import from Canada are infected with the BSE agent. The Exposure
Assessment evaluates the likelihood of exposure, establishment and
spread of the BSE agent in the United States given that it has been
released. The Consequence Assessment addresses the impacts expected if,
as a result of the proposed rule, BSE were to occur in the United
States. Finally, in the Risk Estimation, we combine the findings of the
release, exposure, and consequence assessments to express the overall
risk of BSE in the proposed commodities from the minimal risk region
(Canada).

This risk assessment, according to the approach as it is applied across
a variety of disciplines, breaks down the possible pathways for the
undesired outcome (in this case, the establishment of BSE in the U.S.
cattle population) into a series of steps, or nodes. Some of the nodes
are in series, in that in order for one to occur, a previous one must
have occurred. The likelihood of occurrence of a series of sequential
steps is the product of the likelihood of each of the individual steps
occurring. This multiplicative effect takes place whether or not an
analysis is performed quantitatively or qualitatively. Some steps in the
risk pathways can occur without the occurrence of other steps. These are
said to function in parallel, and are therefore, additive in their
impact on the likelihood of the undesired outcome. Because the impact of
any specific step depends on its relationship to other steps, its
importance to the overall likelihood of the undesired outcome cannot be
understood in isolation from the rest of the pathway. Therefore, in risk
assessment, although we analyze the likelihood of each individual step
in the process, we interpret its significance in the context of the
entire process. For example, in this assessment, we present evidence for
the likelihood of release of infected animals from Canada to the United
States. However, the impact of the amount of infectivity introduced
cannot be understood until it is interpreted together with the outcome
of the Exposure and Consequence Assessments.

History of BSE in Canada

As of October 27, 2006, a total of nine BSE cases of Canadian origin had
been confirmed. This number includes one case of Canadian origin that
was identified in the United States in December 2003. The first native
Canadian case was identified in May 2003, and was followed that year by
the December case identified in the United States. In response to the
finding of BSE in Canadian cattle, the Canadian Food Inspection Agency
(CFIA) intensified their surveillance efforts and have identified seven
additional cases through October 27, 2006.

Epidemiological investigations have shown that BSE initially entered
Canada in the 1980s via an infected animal or animals that were imported
from the UK. It is likely that rendered meat and bone meal (MBM)
produced from these animals were included in cattle feed, a practice
that was permitted at the time, and this practice led to the development
of additional cases of BSE in Canadian-born cattle (USDA 2005a).

Canada imported 182 cattle from the UK between 1982 and 1990. Following
the detection of an imported case of BSE in 1993, all remaining UK
imports were slaughtered and incinerated, or returned to the country of
origin (USDA 2005a). The BSE risk status of the Canadian birth cohorts
was assessed based on demographic factors, age, and the BSE status of
their UK herd of origin. The assessment indicated that of the 52 animals
shipped to the Province of Alberta, three were from cohorts of UK cattle
with BSE. One of these was the animal that tested positive for BSE in
1993; the resulting investigation determined that the other two had
already died and most likely entered the feed processing system prior to
the detection of the first case. Therefore, a likely scenario is that
MBM containing specified risk materials (SRM) from one or more infected
animals contaminated the Canadian feed system and was recycled during
the early 1990s. Considering the average incubation period for BSE, CFIA
believes that Canada's BSE cases represent the second generation (or
amplification cycle) in that country (CFIA 2006).

Investigations conducted in 2003 and 2004, following the diagnosis of an
indigenous case of BSE, revealed geographical proximity among the
origins of all the Canadian BSE cases and the destinations of cattle
imported from the UK (USDA 2005a). The destinations of the UK imports
and origin of the Canadian BSE cases were clustered in a relatively
small geographic area in central Alberta and western Saskatchewan.
Further investigations carried out by CFIA revealed that renderers, feed
mills and farmers across Canada are grouped by geographic and economic
forces into "clusters" (CFIA 2006). Since the distribution of MBM in
Canada is generally localized, the disease was most likely recycled
primarily within a geographic feed zone unless infected cattle and/or
contaminated MBM were moved to other areas. With one exception,
epidemiological investigations completed by October 2006 indicate that
all indigenous Canadian BSE cases were born and spent their first 12
months of life within the cluster area, or were exposed to feed from
within the cluster area (CFIA 2006, CFIA 2006b). The exception was an
approximately 16 year old cow in Manitoba, which was determined to have
a different phenotype than the other cases. The CFIA investigation
reported that this case had a phenotype consistent with a less prevalent
strain of BSE previously reported in Europe and the United States (CFIA
2006b). The detection of additional cases within either this recognized
cluster or further clusters that might be defined in the future cannot
be ruled out. Such detections do not necessarily negate the assumptions
and findings of this assessment.

One of the regional rendering facilities in Alberta processing high risk
BSE animals (downers and dead stock) used a particular low temperature
"vacuum" process that does not reduce BSE infectivity (zero log
reduction). This practice most likely allowed the recycling through the
feed chain of infectious materials from high risk animals and further
contamination of cattle feed prior to implementation of the feed ban.
CFIA concluded that all indigenous Canadian cases detected to date have
been associated with the cluster where this particular low temperature
vacuum rendering system was used (USDA 2005a). After 1997, in compliance
with the feed ban, prohibited ruminant material produced by the low
temperature vacuum rendering system was not used in ruminant feed,
although this ruminant derived material was still available for feeding
to non-ruminants. To deter farmers and ranchers from accidentally or
intentionally feeding prohibited material to ruminants, products
containing ruminant derived material had to be labeled with the caution
statement, "Do not feed to cattle, sheep, deer, or other ruminants."
Therefore, the implementation of the feed ban in 1997 reduced, if not
eliminated, the recycling of BSE infectivity and greatly decreased the
likelihood that cattle born after implementation of the feed ban would
be exposed to the BSE agent.

II. **Hazard Identification**

This analysis focuses on the BSE risk that might be posed by the
importation of live bovines born after the date of an effectively
enforced feed ban, and the importation of certain commodities derived
from cattle (blood and blood products and small intestines other than
distal ileum) into the United States from Canada. The agent of interest
in this analysis causes bovine spongiform encephalopathy (BSE).

BSE is not a contagious disease, and therefore is not spread through
casual contact between animals. Instead, transmission requires that
cattle ingest feed that has been contaminated with tissue from an
infected animal. Several steps must take place for this to happen -- an
infected animal, carrying significant amounts of the infectious agent,
must die or be slaughtered; tissues from that animal that contain the
infectious agent must be sent to a rendering facility; the infectivity
present in these tissues must survive inactivation in the rendering
process; the resulting protein must be incorporated into feed and this
feed must be fed to at least one bovine at a level adequate to result in
infection given that animal's age-specific susceptibility. As will be
discussed later in this document, there are several barriers at
different steps in this process that decrease the possibility of
infection as outlined.

BSE is a progressive neurological disorder of cattle that research
suggests is caused by a pathogenic form of a normally occurring protein
known as a prion (PrP) (Bolton, et al. 1982; Prusiner 1994). BSE belongs
to a family of diseases known as transmissible spongiform
encephalopathies (TSEs). In addition to BSE, TSEs include, among others,
scrapie in sheep and goats, chronic wasting disease in deer and elk,
transmissible mink encephalopathy, and Creutzfeldt-Jakob disease (CJD)
in humans.

The pathogenic form of the prion protein (PrP^Sc^) is both less soluble
and more resistant to degradation than the normal form (Taylor 2000;
Taylor, et al. 1995). The PrP^Sc^ is extremely resistant to heat and to
normal sterilization processes, making it difficult to inactivate with
standard methods used to process human food and animal feed. Although
rendering and other processes can partially inactivate PrP^Sc^, the risk
mitigation strategies (for meat and meat products) rely mainly on the
elimination of tissues and organs known to carry infectivity.

The agent does not evoke a traditional immune response or inflammatory
reaction

(Khalili-Shirazi, et al. 2005), thus reliable ante-mortem diagnostic
tests based on host reaction are not available. Definitive diagnosis
requires post-mortem microscopic examination of brain tissue or
detection of PrP^Sc^ in tissue samples.

The following paragraphs detail the relevant characteristics of BSE,
including transmission, incubation period, tissue distribution, and
infectivity of the BSE agent in cattle, its most common host.

II.A. *Transmission*

The primary source of BSE infection is commercial feed contaminated with
the infectious agent. Scientific evidence (Wilesmith, et al. 1988; 1991;
1992) shows that feed contamination results from the incorporation of
ingredients that contain ruminant protein derived from infected animals.
Standard rendering processes do not completely inactivate the BSE agent.
Therefore, rendered protein such as meat-and-bone meal (MBM) derived
from infected animals may contain the infectious agent. Bans prohibiting
incorporation of mammalian or ruminant protein into ruminant feed are
imposed to mitigate the risk of BSE transmission.

Oral ingestion of feed contaminated with the abnormal BSE prion protein
is the only documented route of field transmission of BSE (Prince, et
al. 2003; Wilesmith, et al. 1988; 1991; 1992). However, results of a UK
cohort study indicated that offspring of BSE-affected dams were at a
higher risk of also developing clinical BSE, suggesting the possibility
of maternal (vertical) transmission (Wilesmith, et al. 1997). These
results are consistent with a rate of maternal risk enhancement of
approximately 10 percent in the offspring born within 12 months of the
dams' onset of clinical signs of BSE. Since the initial cohort study,
modeling studies based on the epidemic data from the UK have indicated
that the cumulative maternal risk is only 1 percent in calves born in
the last 6 months of incubation of the disease in its dam (Donnelly, et
al. 2002). More recent work on cases born after the 1996 feed ban fails
to demonstrate evidence of maternal transmission (Hill 2005). Thus,
although maternal transmission may be possible, more recent
epidemiologic evidence suggests that maternal transmission of BSE is
unlikely to occur at any appreciable level, if at all.

Epidemiological studies and simulation modeling have indicated that most
cases were likely exposed as calves (Wilesmith 1988) with most chances
of becoming infected during the first year of life (Wilesmith, et al.
1992 and 1992a; Ferguson 1997; De Koeijer, et al. 2004). These findings
suggest that susceptibility in cattle declines with age, and, therefore,
young animals are most susceptible. One simulation study suggests that
animals consuming BSE infectivity that are older than four months of age
are less susceptible than younger animals. Specifically, this simulation
estimates that susceptibility declines exponentially after the age of 4
months leveling off at 10 percent of the peak value (De Koeijer, et al.
2004).

Experience in the UK demonstrates that implementation of a
ruminant-to-ruminant feed ban exerts downward pressure on the prevalence
of BSE (Figure 1). Animal feed restrictions began in the UK in July
1988, when the use of ruminant MBM in ruminant animal feed was banned.
In September 1990, the use of Specified Bovine Offals (SBO) was banned
for use in any animal feed. This ban prohibited the use in any animal
feed of bovine tissues with the highest potential concentration of
infectivity. In 1994, the use of mammalian protein -- not just ruminant
protein -- was banned from ruminant feed. In 1996, feeding of any farmed
livestock, including fish and horses, with mammalian meat and bone meal
(mammalian MBM) was completely banned. As a result of these bans to
reduce the recycling of infectivity, the annual incidence of BSE fell by
99.4 percent from 36,680 in 1992 to 203 in 2005 (DEFRA 2006b).

When the UK epidemic is plotted by year of birth, the impact of the feed
ban is striking. Although the data that are presented in the following
figure and table represent the specific situation in the UK[^2] during
the years identified in the graph, we expect similar effects (i.e.,
downward pressure on the prevalence of BSE) in any country that
implements a comparable feed ban.

![](media/image3.wmf){width="6.0in" height="3.798031496062992in"}

**Figure 1.** Confirmed cases in cattle born in Great Britain after feed
ban implementation. **Note:** The first feed ban was implemented in the
summer of 1988 (before fall calving). Source of data represented in
figure and in Table 1: DEFRA 2006a.

The raw data that provided the basis for Figure 1 are reproduced in
Table 1.

**Table 1. Confirmed cases in Great Britain by year of birth, where
known**

  --------------- --------------- ------------------- -------------------
  **Year**        **Cases**       **Year**            **Cases**

  1974            1               1989                12,748

  1975            0               1990                5,747

  1976            2               1991                4,779

  1977            10              1992                3,531

  1978            6               1993                2,997

  1979            41              1994                2,179

  1980            102             1995                1,099

  1981            262             1996                67

  1982            1,394           1997                45

  1983            4,463           1998                37

  1984            8,069           1999                23

  1985            11,071          2000                5

  1986            19,752          2001                5

  1987            36,935          2002                1

  1988            22,266          Unknown birth year  43,340

                                                      

  **Total:                                            
  180,977**                                           
  --------------- --------------- ------------------- -------------------

**Source: DEFRA 2006a.**

Despite the dramatic evidence presented above, as of September 2006, 134
cases of BSE have been detected in UK animals born after the ban (BAB
cases) reinforcement in 1996 (DEFRA 2006). Several analyses of the BAB
cases suggest that the animals were likely to have been exposed to an
exogenous feed source from continental Europe. For instance, based on
the analysis of the first 16 cases (Wilesmith 2002) the author indicates
that an exogenous (non-UK) feedborne source remains the most likely
explanation, since trading of MBM was legally possible at ports of
Continental Europe until the European-wide ban was introduced in January
2001. Significant amounts of ingredients for cattle feed were imported
into the UK before 2001, and cross-contamination of feedstuffs and
ingredients has occurred in a number of other BSE-affected countries. A
recent report (Hill 2005) also indicates the association of BAB cases
with imported feed until controls were strengthened throughout Europe.

II.B. *Incubation*

BSE has a long incubation period. Epidemiological data from the UK
epidemic has demonstrated that, on average, cattle develop clinical
signs four to six years after infection (Bradley 1991; Anderson, et al.
1996), though the incubation period can be longer or shorter than four
to six years. In BSE, as in other TSEs, the total amount of infectivity
in an animal increases throughout the incubation period reaching the
highest load at the end, very close to the death of the animal.
Infectivity is considered to increase exponentially after exposure,
reaching 3 logs less than clinical cases by 70 percent of the incubation
period, and 4.5 logs less than a clinical case at 50 percent of the
incubation period (Comer and Huntley 2003).

The incubation period is thought to be inversely related to dose (e.g.,
low dose exposures have long incubation periods before clinical signs of
disease become apparent). The Department for Environment Food and Rural
Affairs (DEFRA) Veterinary Laboratories Agency (VLA) in the UK has
carried out cattle oral challenge studies to determine the incubation
period for a range of doses of BSE infected cattle brain (Anderson, et
al. 1996). In the first attack rate experiments, groups of 10 calves
were dosed orally with 3 X100g (100g on 3 successive days), 100g, 10g or
1g of brain tissue from clinically sick animals. All animals in the two
higher dose categories (3x100 and 100gr, respectively), 7 out of 9 in
the 10 g, and 7 out of 10 in the 1g trial groups developed clinical BSE.
The incubation period (IP) for the 3X100g ranged between 33 and 42
months. The IP for the 100g was 33 to 61 months; for the 10g was 42 to
75 months; and for the 1g was 45 to 75 months. The remaining animals in
this experiment were killed at 110 months after exposure and showed no
pathological evidence of disease.

The second attack rate experiments extend these findings with lower
doses. As of December 2005, at approximately 93 months post exposure,
the authors have confirmed 3 of 5 animals as positive for BSE in the 1g
trial group (IP 59-73 months), 6 out of 15 animals in the 0.1g group (IP
55-90 months), 1 out of 15 in the 0.01g group (IP 56 months), and 1 out
of 15 in the 0.001g group (IP 68 months) (Matthews 2005 personal
communication). The study is ongoing.

II.C. *Tissue distribution and infectivity*

Most of the information on the development and distribution of tissue
infectivity in BSE infected cattle has been derived from experimental
pathogenesis studies conducted in the UK (Wells, et al. 1994; 1998;
1999). In these studies, cattle were deliberately infected with BSE
through oral exposure to the brain tissue of cattle with confirmed BSE.
Subsets of the experimentally infected cattle were killed at regular
intervals as the disease progressed. At each interval the tissues of the
infected cattle were examined for histopathological changes consistent
with BSE and for abnormal prion proteins. Also, at each interval, a
mouse assay was done -- i.e., tissues of the BSE infected cattle were
injected intracerebrally and intraperitoneally into mice to identify
those tissues of cattle containing infectivity.

The pathogenesis studies involved 30 animals, each of which received a
single dose of 100g of infected brain at 4 months of age (Wells, et al.
1994; 1998; 1999). This dose is probably 10 -100 times greater than that
associated with field exposure via feed (DEFRA 2005). The studies
demonstrate that in cattle infected with BSE, the total amount of
infectivity in the animal, as well as the distribution of infectivity in
the animal\'s body, change over time (Wells, et al. 1994; 1998; 1999).
The highest levels of infectivity were detected in the brain and spinal
cord at the end stages of disease. Some cattle exhibited clinical signs
of BSE as early as 35 months post oral exposure to the BSE agent. By 37
months post oral exposure, all five animals that were still alive
demonstrated clinical evidence of BSE. Infectivity was found in cattle
with clinical signs of BSE in the brain, spinal cord, dorsal root
ganglia (DRG)[^3], trigeminal ganglia, and the distal ileum of the small
intestine.

BSE infectivity was demonstrated in the brain, spinal cord, and DRG as
early as 32 months post oral exposure to the BSE agent in some cattle
(Wells, et al. 1994; 1998; 1999). Infectivity was demonstrated in these
tissues three months before animals began to develop clinical signs of
the disease. Infectivity was demonstrated in the distal ileum of cattle
6 to 18 months post oral exposure to the BSE agent and again at 38
months and 40 months post oral exposure.

As explained by DEFRA and by the European Commission's Scientific
Steering Committee, a second phase of the pathogenesis studies, which
uses a cattle bioassay as an endpoint, is being conducted to ensure that
low levels of infectivity that may not have been detected in the first
phase using the mouse bioassay are not missed (DEFRA 2005; EC SSC
2002b). This second phase of the study is still underway and is not
expected to be completed for several more years. In the cattle bioassay,
tissues from the same cattle orally exposed to BSE in the earlier
pathogenesis studies, were injected directly into the brain of BSE-free
cattle (DEFRA 2005). This method is considered to be several
hundred-fold more sensitive in detecting BSE infectivity than the mouse
bioassay (DEFRA 2005). Preliminary results from the cattle bioassay
study demonstrate that, in addition to the materials that were found to
contain infectivity when the mouse bioassay was used, the tonsils of
calves 10 months post oral exposure to the BSE agent also contain
infectivity. However, because only one of five animals injected with
tonsil material from infected animals developed clinical BSE at 45
months post-inoculation, the level of infectivity in the tonsils appears
to be very low.

In addition to these studies on experimentally infected cattle,
distribution of tissue infectivity has also been studied in cattle
exposed to BSE under field conditions. In these animals, at the end
stages of the incubation period with demonstrated clinical signs, BSE
infectivity has been confirmed by mouse bioassay only in the brain,
spinal cord, and retina of the eye (EC SSC 2001).

In a recent study, mice, genetically engineered to be highly susceptible
to BSE and to overexpress the bovine prion protein, were inoculated with
tissues from an end-stage clinically affected BSE-infected cow
(Buschmann and Groschup 2005). The sensitivity of these mice to
infection is significantly greater than other mice panels used in
bio-assays, and the sensitivity is even greater than that of cattle by
approximately 10-fold. This study demonstrated low levels of infectivity
in the facial and sciatic nerves of the peripheral nervous system, when
injected into these highly sensitive mice. While these are interesting
findings that can help further characterize the pathogenesis of BSE,
they cannot be easily extrapolated into the context of the risk
presented by natural exposure pathways. The findings may be influenced
by the overexpression of prion proteins in these genetically engineered
mice. Any apparent levels of infectivity are low in these extremely
sensitive mice and would be even lower in other species such as cattle.
Moreover, the route of administration to the mice was both
intraperitoneal and intracerebral, both of which are very efficient
routes of infection as compared to oral consumption. Given all of these
factors, we conclude that there is not sufficient information in this
study to alter our understanding of the epidemiologically significant
distribution of BSE infectivity in cattle.

The amount and distribution of infectivity in specific tissues from an
infected cow have been estimated by Comer and Huntley (2003) in their
evaluation of the available literature. Those summary results, presented
in Table 2, describe distribution of infectivity in various tissues,
*i.e.*, brain, spinal cord, DRG, trigeminal ganglia, tonsil, and distal
ileum, of a BSE-infected cow. The table uses an estimated weight of each
tissue in grams, the number of estimated cattle oral infectious dose-50
(ID~50~) units[^4] per gram, and the total number of cattle oral ID~50~
units attributed to each tissue to estimate a percentage of cattle oral
ID~50~ units for each tissue.

**Table 2. Infectivity in a clinical case of BSE (cattle oral ID~50~)**

  ------------------------ ------------ ----------------- --------------- --------
  **Tissue**               **Weight**   **Infectivity**                   **%**

                           g/animal     ID~50~/g          ID~50~/animal   

  Brain                    500          50                25,000          60.2

  Spinal cord              200          50                10,000          24.1

  Dorsal root ganglia      30           50                1,500           3.6

  Trigeminal ganglia       20           50                1,000           2.4

  Tonsil                   50           0.005             0.25            0.0

  Distal ileum             800          5                 4,000           9.6

  **TOTAL**                **1,600**                      **41,500**      
  ------------------------ ------------ ----------------- --------------- --------

**Source: Comer and Huntley 2003.**

The table shows that 90 percent of the infectivity is associated with
central and peripheral nervous system tissues, i.e., brain, spinal cord,
DRG, and trigeminal ganglia. About 10 percent was associated with the
distal ileum. Minimal infectivity was associated with tonsils in a
clinically affected animal.

III. **Release Assessment**

In this section of the risk assessment we present evidence on the
likelihood of each of the evaluated commodity groups to introduce BSE
infectivity into the United States. To do so, we first evaluate the
prevalence of BSE in Canada, using both quantitative and qualitative
approaches. We then evaluate the specific risk reduction steps
associated with each of the commodity groups: live bovines, blood and
blood products, and small intestines other than the distal ileum. We
also present numeric estimates of projected live bovine imports. We then
combine the information presented in these sections to assess the
release of BSE infectivity associated with each commodity group. All
commodities are assessed qualitatively. In order to inform the
quantitative exposure model described in Section IV.A., release of BSE
via live bovines is assessed quantitatively, as well.

III.A. *Estimation of BSE Prevalence in Canada*

The purpose of this section is to estimate the prevalence of BSE in the
adult cattle population of Canada. The detection of Canada's first
native BSE case was confirmed on May 20, 2003. As of October 27, 2006, a
total of nine BSE cases of Canadian origin had been confirmed in North
America (CFIA 2006). This total includes a case of BSE that was
confirmed in Washington State on December 25, 2003. By comparison, the
UK had detected 184,453 cases of BSE through September 2006 (OIE 2006).

Prevalence is defined as the proportion of infected animals in a
population. Although the simplest approach to the estimation of
prevalence is to calculate this proportion directly (e.g., \# identified
cases/# samples tested), the limitations of current testing methodology
for BSE make this approach less meaningful. Like many transmissible
spongiform encephalopathies (TSEs), BSE has an incubation period of
several years. Current technology can only detect the disease very close
to the end of the incubation period, up to 3 months before an animal
begins to exhibit clinical signs. Therefore, infected but preclinical
animals would not be detectable. The number of BSE cases detected
through surveillance understates the disease prevalence because exposed
animals may be incubating disease which would not always be detectable
with current testing methodology. Furthermore, surveillance will miss a
proportion of detectable (clinical or late incubation) cases. Therefore,
statistical methods are applied to the available epidemiologic and
surveillance data to estimate, with attendant uncertainty, the
prevalence of BSE in Canada.

We have used two related, but distinct methods to estimate BSE
prevalence in Canada (Attachment 1). Given its international prominence,
we consider the European Union (EU) BSurvE model (Wilesmith, et al.
2004, 2005), recently developed for the purpose of estimating BSE
prevalence in national herds. The BSurvE model is noteworthy for its
sound epidemiologic structure, including stratifying cattle by age and
cause of death and accounting for the relative likelihood of detecting
BSE in various strata (EFSA 2004). The other prevalence estimation
method used in this document, referred to as the Bayesian Birth Cohort
(BBC) model, takes advantage of the BSurvE model structure to calculate
BSE surveillance point values (random sample size equivalents)
represented by targeted Canadian sampling of certain groups of cattle in
which BSE cases are more likely to be detected. The BBC model adopts a
Bayesian statistical framework to incorporate prior information about
the decreased incidence of BSE observed in animals born after the
initial ruminant-to-ruminant feed ban introduced in the UK in 1988. For
the purposes of comparison and sensitivity analysis, the prevalence of
BSE in Canada also is estimated using BSurvE.

The identical methodologies were used in the recently published and
peer-reviewed U.S. BSE Prevalence document (APHIS CEAH 2006). The
reviewers found that these models were statistically and
epidemiologically sound.

> III.A.1. [BSurvE Model]{.underline}

We use as a basis for our prevalence estimates the "BSurvE" model
developed in the EU (Wilesmith, et al. 2004). This model provides the
benefit of combining surveillance data, population demographics, and
knowledge of the disease pathogenesis with evidence of the relative
likelihoods of infectivity in various sub-populations, to estimate BSE
prevalence in the entire cattle population. Moreover, the prevalence
estimate includes all infected cattle regardless of whether they are at
a stage at which the disease is detectable.

Specifically, BSurvE stratifies cattle by age and cause of death
(healthy slaughter, fallen stock, casualty slaughter, or clinical
suspect) and accounts for the relative likelihood of detecting BSE in
various strata. The model uses epidemiologic information of the disease
that was accumulated during the UK and European outbreaks to predict
parameters such as incubation period of BSE, probable length of an
infected animal's life, and the dynamics of disease expression in
infected animals. It combines this information with the age distribution
of a country's national herd and its surveillance test data to achieve a
set of point values for samples taken from cattle of different age and
cause of death strata called surveillance streams. The points
represented by an animal tested for BSE are based on the relative
likelihood that the disease would be detected in an animal leaving the
herd at a particular age and by a particular surveillance stream. Under
this scheme, one point is equivalent to an animal randomly selected for
testing from the national herd (Wilesmith, et al. 2004). We obtain the
BSE surveillance points used as inputs to the BSurvE prevalence
estimation model using BSurvE Version 06.03. The BSurvE spreadsheet
model and documentation are available on the BSurvE Web site
([www.bsurve.com](http://www.bsurve.com/)). The Web site includes
updates made to the BSurvE model, documentation (Wilesmith, et al. 2004;
2005) that provides detailed description of the underlying functions of
the model, and step by step user instructions.

> III.A.2. [Bayesian Birth Cohort Model (BBC): Inclusion of feed ban
> data]{.underline}

In order to halt the spread of BSE, all countries known to have had BSE
cases have banned the feeding of ruminant protein to ruminants. Evidence
gathered from countries, such as the United Kingdom, describes the
decline in BSE cases following implementation of such feed bans
(Schreuder and Wilesmith 1997). Therefore, Bayesian methods, which allow
the combination of different types of information, can be used to
incorporate this evidence with the surveillance data collected by a
different country -- in this case, Canada.

Because the provisions of the Canadian ruminant feed ban introduced in
1997 were comparable to or more restrictive than the UK feed ban in
place from 1988 to 1994, we estimate the effect of a feed ban on BSE
prevalence in Canada to be proportional to that observed in the UK
during those years. The initial UK feed ban imposed in 1988 prohibited
the inclusion of ruminant MBM in ruminant feed (DEFRA 2006c). In
comparison, the Canadian feed ban prohibits the feeding of most
mammalian proteins (with exceptions) to ruminants (CFIA 2002), and is
therefore equivalent or more restrictive than the initial UK feed ban.
In 1994, the UK requirements became more restrictive by prohibiting the
use of any mammalian protein in ruminant feed. Additionally, U.S.
veterinary epidemiologists reviewed records and conducted site visits to
Canadian facilities to evaluate the efficacy of the Canadian ban and
concluded that compliance with the feed ban was good, and that the feed
ban was effectively enforced (USDA 2005). Although the degree to which
the Canadian ban was able to reduce BSE transmission is difficult to
measure directly, Cohen et al. (2001; 2003) concluded that the U.S.
ruminant feed ban would rapidly decrease BSE prevalence following the
ban even with a substantial initial infusion of infectivity. Since the
U.S. and Canadian bans are similar to each other, it is reasonable to
conclude that the findings of Cohen et al. (2001; 2003) would likewise
apply to Canada.

The Bayesian Birth Cohort (BBC) model provides a more precise estimate
of BSE prevalence in Canada by combining the epidemiologic theory
underlying the BSurvE model with information about the effect of the
feed ban on prevalence, as well as with surveillance data. Like BSurvE,
the BBC prevalence estimate includes all infected animals in the
standing adult cattle population of Canada, whether or not they are
detectable and uses BSurvE's methodology for obtaining BSE surveillance
points, described above. As a starting point, the BBC model assumes that
the BSE prevalence in cohorts born prior to the feed ban could range
from 0 to 100 percent (i.e., the prior assumption was that prevalence is
uniformly distributed between 0 and 100 percent). The prior assumption
about prevalence is then modified with each iteration based on a
constant prevalence before the feed ban, a decline after the ban
proportionate to the UK, and the accumulated surveillance data. The
model uses the total number of BSurvE points from each of the 1993-2004
birth cohorts that were tested by Canadian surveillance over a 7-year
period ending August 15, 2006 as evidence for estimating the current
prevalence.[^5] Prevalence of infected adult cattle alive on August 15,
2006 was estimated from the Bayesian model as the weighted sum of the
individual birth cohorts' prevalence levels, where the weights are the
proportion of infected animals born into each cohort that remain alive
in August 2006.

The BBC model was implemented using two Bayesian analytical methods:
Gibbs sampling and Sampling-Importance-Resampling (SIR). Gibbs Sampling
is a Monte Carlo Markov Chain (MCMC) statistical method (Vose 2000).
MCMC methods are based on an iterative updating scheme that is repeated
until the sequence of parameter vectors converges. We first estimate the
BBC model parameters by performing Gibbs Sampling using the WinBUGS
statistical application Version 1.4.1 (MRC Biostatistics Unit 2004).
Documentation for the WinBUGS application is available at
[www.mrc-bsu.cam.ac.uk](http://www.mrc-bsu.cam.ac.uk/). Using the same
model structure and inputs, an alternative Bayesian method was used to
verify the BBC model results obtained using WinBUGS. In contrast to the
iterative Gibbs sampling method, Sampling-Importance-Resampling (SIR) is
a noniterative Bayesian method. See the Prevalence document
(Attachment 1) for details of the Bayesian Birth Cohort model, including
the WinBUGS code and a description the SIR algorithm used to implement
it.

III.A.3. [Summary of assumptions and methods used in the Canadian
calculations]{.underline}

Detailed explanation of the following assumptions and analytic
methodology is included in Attachment 1.

1.  As is true for many countries, precise data for age structure of the
    Canadian population is not known. However, the population structure
    was estimated based on data from Statistics Canada
    ([http://www.StatCan.ca](http://www.StatCan.ca/) ) and further
    verified by comparing the results with the age distribution
    predicted by the Harvard risk assessment for the U.S. population
    (Cohen et al. 2001; 2003). This distribution was then used for the
    "idealized" age distribution section of the BSurvE model.

2.  BSurvE requires that the test data be stratified by age. However,
    prior to recent revisions to the OIE code (OIE 2006a), age
    stratification data were not an essential component of BSE
    surveillance, and thus were not routinely captured. In Canada,, age
    associated data are available, however, for approximately 50 percent
    of the BSE tests undertaken within CFIA's TSE network laboratories
    in 2004 and 2005. This subset represents over 20,000 animals.
    Considering the large number of animals with age data and that there
    appeared to be no significant differences in age related trends
    between these years, age stratification estimates for each
    surveillance stream was determined by pooling the two years of data.
    These estimates were then used to stratify the surveillance results
    of animals for which age data were not available.

3.  The December 2003 case discovered in the United States was included
    in the prevalence calculation as a Canadian case, however, no other
    surveillance data for Canadian cattle in the United States were
    included. Thus, the positive data point was included but none of the
    corresponding negative results were considered in this analysis. The
    inclusion of positive but not negative data from the United States
    acts to over-estimate the prevalence estimate for Canadian cattle.

4.  BSE tests that were done as part of the epidemiologic investigations
    of BSE cases in Canada did not meet Canada's BSE surveillance
    criteria for the targeted sample population and were therefore
    excluded from the input data used to estimate the Canadian
    prevalence. Thus, only those samples that were collected for the
    purpose of Canada's BSE surveillance were included in the national
    prevalence estimate. Although the negative samples from healthy
    animals tested in the follow-up investigations were not used for
    estimating the prevalence of BSE in Canada, they do increase
    confidence that no unidentified cases are present in local
    association with the positive animals.

5.  Exit constants were set at the default of the BSurvE model which
    reflects the United Kingdom and European experience. These constants
    are primarily influenced by disease dynamics (BSurvE.com 2005) and
    are assumed to have minimal influence on North American assessments
    based on current knowledge of BSE.

6.  Clinical suspects were identified from the Canadian surveillance
    database based on the clinical signs and history recorded by field
    veterinarians in the submission record. They were not defined by
    "submission reason" because this category could allow samples to be
    designated as clinical suspect without supporting information from
    the veterinarian. Sample submission data that reported clinical
    signs listed on the CFIA Web site as compatible with the clinical
    suspect definition were electronically selected from the CFIA
    database. The selected records were further reviewed by BSE
    epidemiologists from CFIA and USDA to remove animals with acute
    neurological conditions or other diseases that explained alternate
    diagnoses for the neurological signs reported. The final set of
    samples were those that met criteria described in the OIE code for
    classification as clinical suspect animals.

7.  The initial UK ruminant feed ban substantially decreased the number
    of new cases in subsequent birth cohorts. Similar to the approach
    taken in estimating BSE prevalence in the United States (APHIS
    2006), we assume that the Canadian feed ban during its first five
    years would reduce Canadian prevalence proportionately to the
    observed reduction in UK prevalence during the first five years of
    the UK ban: 1989 to 1994, during which the UK feed ban was most
    similar to the current Canada feed ban. We therefore incorporate
    evidence from the UK reflecting the drop in prevalence following
    their feed ban into an estimate of Canadian BSE prevalence. We
    further note that as our knowledge of Canada's prevalence improves
    through continued surveillance efforts, the statistical contribution
    of the additional UK evidence diminishes.

8.  Analysis of the Canadian BSE surveillance data provides no
    statistical basis for distinguishing BSE prevalence among birth year
    cohorts (Attachment 1). Therefore we calculated a single prevalence
    estimate for the entire population.

## III.A.4. [Results of prevalence estimation]{.underline}

The table below presents the expected prevalence estimates in the
standing adult cattle population of Canada in 2006, as well as their
respective 95^th^ percent confidence levels. The BSurvE "Prevalence B"
estimate is presented for comparison because it is calculated without
incorporating evidence about the effect of the feed ban beyond that
reflected in the surveillance data. See Attachment 1 for details of the
BSurvE model and inputs.

Table 3. Results of prevalence calculation.

+-----------------------+----------------------+----------------------+
| **Prevalence in adult | **Bayesian birth     | **BSurvE Prevalence  |
| population**          | cohort method (BBC)  | B estimate without   |
|                       | with UK feed ban     | including feed ban   |
|                       | data**               | data**               |
+-----------------------+----------------------+----------------------+
| **Expected value**    | 0.68\*10^-6^         | 3.9\*10^-6^          |
|                       |                      |                      |
| **(mean)**            |                      |                      |
+-----------------------+----------------------+----------------------+
| **95^th^ percent      | 1.1\*10^-6^          | 6.8\*10^-6^          |
| confidence level**    |                      |                      |
+-----------------------+----------------------+----------------------+

> III.A.4.a. *Application of Prevalence Estimates to the Exposure
> Assessment*

It is important to note that the estimated prevalence distribution
presented here represents parameter uncertainty. For a fixed prevalence
value, the number of infected cattle in the population would still vary
randomly over time. Assuming a constant probability of infection, the
random variability in the number of BSE infected animals in the adult
cattle population would follow a binomial distribution. For a large
sample size and low prevalence values, the Poisson approximates the
binomial variability distribution and is incorporated in the model
supporting the exposure assessment for live bovines (Section IV.A. and
Attachment 2) to represent variability around the prevalence estimates
generated here.

Moreover, it is important to recognize that our models provide a robust
estimate of the prevalence in Canada at this point in time. They do not
project changes in prevalence expected in the future. Empirical evidence
from the UK has demonstrated and simulation studies have reinforced that
implementation of a ruminant to ruminant feed ban leads to continued
decrease in prevalence over time (Cohen, et al. 2001; 2003; DEFRA 2006,
EC 2003; 2005), yet the methods we use to estimate the prevalence of BSE
in Canada cannot predict such future changes in prevalence. We can,
however, use these August 15, 2006 prevalence estimates in two different
ways. First, we can use them to provide a current estimate of possible
release via live animal imports in the first year of our analysis, and
we can qualitatively consider subsequent years of decreasing prevalence
in our exposure assessment. Second, as we allow for less likely outcomes
over the 20 year period of the analysis, we can also use these
prevalence estimates as numeric surrogates for the release input
parameter of the exposure model (Attachment 2) which we use to inform
our exposure assessment (Section IV.A.).

Like the effects in the UK described in the Hazard Identification
(Section II), similar effects of a feed ban have been seen in the EU.
The apparent number of cases of BSE identified in the EU-15 Member
States has decreased every year since 2001. Feed ban legislation was
initially adopted within the EU in August 1994, and was gradually
strengthened over the intervening years until the current requirements
took effect in 2001. While the legislation took effect upon publication
in 1994, it is recognized that initial implementation was inconsistent
and some efforts were not immediately effective. In fact, this initial
inconsistency, especially regarding cross-contamination, led to
increasingly stringent feed ban requirements (EC 2003; 2005).
Nevertheless, the implementation of active surveillance efforts within
the EU in 2001 documents the effects of the initial feed ban. Allowing
approximately 5-6 years before being able to observe the effects of the
feed ban on diagnosed cases, the decreasing number of bovine cases
reflects the impact of the initial feed ban. An alternative way to
evaluate the effects of the feed ban is to observe the number of cases
by year of birth. In the EU, the peak number of cases was born in 1995
followed by a significant drop, reflecting the effect of the feed ban
(EC 2005a).

Given this demonstrated experience regarding the effects of a feed ban,
it is extremely likely that the prevalence of BSE in Canada will
continuously decrease over the next several years. The Canadian
government has reached the same conclusion in their analysis and further
predicts the ultimate eradication of the disease (CFIA 2004; 2006).
Therefore, we conclude that it is highly probable that the prevalence
will continue to decrease from the currently low level estimated here.

III.B. *Release of infectivity via the various commodities proposed for
importation from*

*Minimal Risk Regions*

III.B.1. [Release of BSE infectivity via live bovines]{.underline}

The OIE establishes standards for the international trade in animals and
animal products. The OIE *Terrestrial Animal Health Code* (Chapter
2.3.13) allows trade in live cattle from regions that have reported BSE
and have an effective feed ban in place, provided that the cattle were
born after the date when the feed ban was effectively enforced.

As described in the Hazard Identification section of this document, BSE
is spread under field conditions when cattle consume feed contaminated
with the BSE agent. Transmission can be prevented by excluding
potentially infected materials from ruminant feed. Therefore, bovines
born after the date when a ruminant-to-ruminant feed ban was effectively
enforced are unlikely to have been exposed to the BSE agent.

Although the proposed rule addresses the importation of live bovines, we
acknowledge that a very small proportion (roughly 2500 of 1.3 million,
or 0.2 percent as discussed in Section III.C.) of these animals will be
bison. Therefore, we focus this discussion on the impact of the "date of
the effectively enforced feed ban" mitigation on cattle, rather than on
bovines in general. We have no reason to believe that these conclusions
do not also apply to bison, however.

In the sections that follow, we discuss the feed ban and related
activities in Canada that mitigate the risk that cattle exported from
Canada to the United States would be exposed to the BSE agent. Then, in
order to increase the certainty that animals eligible for import to the
United States have been subject to the fully implemented Canadian feed
ban, and to be consistent with the OIE standard described above, we
apply the gathered evidence to determine the date when we are confident
that an effectively enforced ban was achieved.

As part of previous rulemaking, an evaluation was done that concluded
that the feed ban was effectively enforced (APHIS 2004). This conclusion
was based on consideration of the regulations in place based on
statutory authority, adequate infrastructure to implement the
regulations, and evidence of implementation and monitoring (i.e.,
compliance inspections, training and records).

After this determination has been made, then consideration can be given
to when full implementation is achieved. Full implementation and
effective enforcement would be achieved after completion of the initial
(or practical) implementation period and sufficient time has elapsed to
allow most feed products to cycle through the system. The practical
implementation period, which begins when the regulations are initially
put in place, can be determined by evaluating implementation guidance
and policies, such as allowing grace periods for certain aspects of the
industry. In addition, the time necessary for initial education of
industry and training of inspectors must be considered. After the
practical implementation period is defined, then we considered a
sufficient time period subsequent to this to allow most feed products to
cycle through the system, given the management practices in the country.

Based on this evaluation, APHIS concludes that cattle born in Canada on
or after March 1, 1999 can be imported into the United States with a
very low risk that they have been exposed to the BSE agent.

> III.B.1.a. *Feed ban in Canada*

In 2004, USDA conducted a risk analysis to evaluate the BSE risk from
ruminants and ruminant products imported from regions presenting a
minimal BSE risk, and to evaluate whether Canada can be classified as a
minimal risk region (APHIS 2004). As part of the risk analysis, USDA
evaluated a series of measures introduced in Canada to prevent the
feeding of ruminant proteins to ruminant animals. USDA considered the
compliance activities reported by the CFIA as well as epidemiological
information as evidence of the effectiveness of the feed ban. The risk
analysis concluded that compliance with the feed ban was good, and that
the feed ban was effectively enforced.

In response to the detection of two additional BSE cases in Canada, in
January 2005, USDA reassessed the oversight of Canada's feed ban. Based
on review of inspection records and on-site observations, USDA confirmed
that Canada has a robust inspection program, that overall compliance
with the feed ban is good, and that the feed ban is reducing the risk of
transmission of BSE in the Canadian cattle population (USDA 2005).

In addition to the USDA audit of the Canadian feed ban, CFIA conducted
its own review in 2005, and concluded that the ban is providing an
effective barrier that is contributing to reducing the BSE risk in the
country to an extremely low level (CFIA 2005).

Canada's feed ban was also a central issue in an investigation conducted
by the USDA in 2005 of the epidemiology of BSE in North America (USDA
2005a). In 2006, Canada released the assessment of the North American
cases of BSE diagnosed from 2003 to 2005 (CFIA 2006). This report
describes the epidemiological investigation of cases as well as their
association with potential sources of infectivity. Information from the
epidemiological investigations to date and the 2005 feed ban reports are
incorporated into the elements of our discussion below regarding the
efficacy of Canada's feed ban.

In June 2006, CFIA finalized regulatory amendments to enhance their feed
ban. These require, among other things, the removal of specified risk
materials from all animal feeds, pet food, and fertilizer. These
regulations will not be effective until July 12, 2007, and therefore
they are not considered in the following discussions.

> III.B.1.a.1. *[Implementation of the Feed Ban]{.underline}*

On August 4, 1997, Canada issued regulations prohibiting the use of
mammalian protein in ruminant feeds as follows: "Any feed that is, or
that contains any prohibited material originating from a mammal (with
exceptions) shall not be fed to a ruminant" (CFIA 2002; Health of
Animals Regulations, Part XIV, Sections 162-171). The ban provided
exceptions for milk, blood, gelatin, and protein derived solely from
porcine or equine sources. Canadian feed regulations also prohibit the
use of plate waste[^6] and poultry litter in ruminant feed. Canada's
feed ban prohibits feeding of most mammalian proteins to ruminant
animals, such as cattle, sheep and goats.

Elements of the feed ban include requirements for labeling and
record-keeping. Feeds for equines, porcines, chickens, turkeys, ducks,
geese, ratites or game birds, containing prohibited materials, must be
clearly labeled with the following cautionary statement, "Do not feed to
cattle, sheep, deer or other ruminants." Labels for bulk feed are
stapled to the invoice and shipping documents. Ruminants may be fed pure
porcine meal, equine meat meal and nonmammalian protein meal (fish,
avian), as well as milk, blood, gelatin, rendered animal fat and any
products produced from these materials from all species.

Feed manufacturers, renderers, retailers, and livestock producers must
document their production procedures and feeding practices to verify
their compliance with the feed ban. Feed manufacturers must keep records
regarding the composition, identity, and distribution of all feeds for
the species named in the regulations. Renderers, feed manufacturers and
farmers must take steps to prevent the incorporation or
cross-contamination with material prohibited under the feed ban into
ruminant feed. To prevent the misfeeding of prohibited material to
ruminants, users of livestock feed must keep labels or invoices from all
purchased feeds containing prohibited material; these records must be
kept for two years. Prohibited material may be fed to non-ruminant
animals such as poultry and swine. CFIA expected that these practices
and requirements would become more efficient and familiar over time as
evidenced by the phase-in periods described below.

Beginning as early as 1996, as the ban was being formulated, government
officials in Canada met extensively with feed mills and the rendering
and livestock industries to educate and inform all sectors about the
upcoming regulatory requirements (CFIA 2005). As noted above, Canada
published its regulations banning prohibited material in ruminant feed
on August 4, 1997.

Although the regulations came into force the same day, full
implementation was a gradual process. From the outset, CFIA recognized
that a phase-in period would be required before prohibited materials
that were already in feed channels would be exhausted, and labeling and
record keeping requirements would be met. It was estimated that it would
take approximately 30 days for feed mills and retailers to use up and
distribute existing supplies of "old" product (i.e., unlabeled feed
intended for ruminants and produced using ruminant MBM); 60 days to add
the caution statement to labels, invoices, and production records; and
60 days for farms to use up their stores of "old" product (USDA 2005a).
All retailers were given until September 3, 1997 to use or distribute
feed already produced. Feed manufactures received a grace period until
October 3, 1997 to comply with labeling requirements. Livestock
producers were given a grace period until October 3, 1997 to use the
feed manufactured and purchased prior to the feed ban. However, feed
tracing associated with the epidemiological investigations of one of the
Canadian BSE cases suggested that feed produced prior to implementation
of the feed ban may have been available at feed stores and/or on-farm
several months longer than anticipated. Therefore, CFIA considered that
the "practical implementation period" may have been up to 6 months after
the date of the ban (USDA 2005a).

Implementation of the feed ban required addressing the four major
components of the feed chain involving the use of ruminant derived
proteins in animal feeds, and preventing cross contamination of cattle
feed with prohibited material or misfeeding of prohibited material to
cattle. Briefly, these components are the collection of inedible
products from slaughter and/or dead stock and transport of these
materials to the rendering plant; processing by the rendering plant of
inedible material into products (primarily MBM) and transport to feed
mills; mixing by the feed mill of the rendered products with grains and
other ingredients into feeds for a variety of animals (the highest
volume being used in feed for poultry); and distribution to farms where
these feeds may be used with or without further mixing. Specific control
measures appropriate to each of these components had to be developed and
incorporated into the feed ban requirements.

> III.B.1.a.2. *[Rendering industry]{.underline}*

The rendering industry is crucial in reducing the risk of transmitting
BSE infectivity, not only because of its role in inactivation of the BSE
agent, but also because it serves as a critical control point for the
redirection of ruminant protein away from cattle feeds. Since 1998, all
Canadian rendering facilities have been subject to annual inspections
and permitting (USDA 2005). Three types of permits are issued, allowing
companies to produce only non-prohibited material, only prohibited
material, or both non-prohibited and prohibited material (USDA 2005).
Permitting requires implementation of manufacturing controls (such as
Good Manufacturing Practices and risk-based HAACP[^7]), record-keeping
(for both production and distribution) and labeling requirements ("Do
not feed to cattle, sheep, deer or other ruminants" on labels and
invoices for all prohibited material) directed at preventing
cross-contamination or misfeeding.

> III.B.1.a.3. *[Addressing cross-contamination]{.underline}*

As mentioned earlier, renderers, feed manufacturers and farmers must
take steps to prevent cross-contamination of ruminant feed with material
prohibited under the feed ban. Such contamination can be prevented by
having dedicated processing lines or facilities which use only
prohibited or non-prohibited material. If a facility handles both
prohibited and non-prohibited material, procedures must be established
and maintained to conduct flushing and/or clean-out between batches of
product to prevent cross-contamination.

Investigation of the BSE cases born in 2000 and 2002 suggest that these
animals were most likely exposed during their first year of life to feed
contaminated during processing (CFIA 2006b). In particular, the reports
of the investigations identified incidents of concern in which ruminant
feed was processed or transported immediately following the processing
of non-ruminant feed containing prohibited material. Such incidents were
in contravention of Canadian regulations, which require flushing and/or
clean-out between batches if ruminant feed is processed on the same
lines as feed containing prohibited material.

The detection of BSE in an animal born after the date the feed ban was
implemented does not indicate an overall failure of the measures in
place to reduce and eventually eradicate the disease from a country. In
most other countries that have experienced cases of BSE, similar events
have occurred. Nevertheless, despite such occurrences, a feed ban will
be effective in decreasing the transmission of disease (Heim and Kihm
2003).

The feed industry has taken a number of aggressive steps to comply with
measures in the feed ban designed to reduce the risk of
cross-contamination of feed for cattle with prohibited material.
Recently, both the United States and Canada reviewed the changes made to
industry procedures and government inspectional oversight to meet the
feed ban requirements at feed mills and rendering facilities (USDA 2005;
CFIA 2005). These reviews demonstrated, for example, that the rendering
industry has moved toward establishment of dedicated facilities or
dedicated processing lines within rendering facilities (USDA 2005; CFIA
2005). Of the 29 rendering facilities in Canada, six handle both
prohibited and non-prohibited material. Of those six, four use dedicated
processing lines (CFIA 2005). According to CFIA's reports, the feed
manufacturing industry has also moved toward dedicated feed
manufacturing facilities. Per the most recent review, 94 (17 percent) of
the 550 commercial feed mills that handle prohibited material also
manufacture feeds for ruminants (CFIA 2005). These actions, in addition
to the labeling and record keeping requirements for all products
containing prohibited material, decrease the likelihood of contamination
of ruminant feeds with prohibited material. HACCP programs, certified
through the Animal Nutrition Association of Canada, have been developed
and implemented at commercial feed mills producing over 60 percent of
total commercial feed production (McGrath 2004). Under these programs,
feed mills have incorporated elements of the feed ban into their
manufacturing process that are supported by additional training of
employees, developing standard operating procedures, and maintaining
appropriate records.

> III.B.1.a.4. *[Education and industry awareness]{.underline}*

The Canadian federal government, through the CFIA, is responsible for
regulating and overseeing inspection of the animal feed industry. CFIA
developed education and training initiatives shortly after the feed ban
was first proposed in 1996 and began educating their own inspection
force, as well as the feed industry, livestock producers, and
veterinarians about the impending regulations and the steps necessary to
implement them. The Feed Program Inspection Manual, the main training
tool for CFIA inspectors, was supplemented with newly developed
guidelines, standards and procedures to facilitate uniform
implementation of the new feed ban inspection tasks. Inspections were
increased. Workshops were held in all regions to cover the controls and
processes required to comply with the feed ban's requirements (CFIA
2005).

Once the feed ban regulations were in place, CFIA continued to interact
with and educate feed manufacturers, renderers, feed retailers, and
producers to support implementation of the new regulations. These
efforts included workshops; posting the new regulations on the CFIA Web
site; and preparing and disseminating bulletins and press releases to
all affected parties. Broad educational outreach by CFIA about BSE was
made to government and private veterinarians, provincial, federal and
university diagnosticians, producers, and workers involved in all
aspects of the livestock industry (CFIA 2005). The cumulative effect of
these educational efforts has been to support and enhance the
effectiveness of the feed ban by ensuring that each sector of the
impacted industry has taken the steps necessary to implement and sustain
an effective feed ban, understand the impact of BSE on Canadian
agriculture, and eliminate exposure of the Canadian cattle population to
BSE infectivity. It is likely that the high level of awareness fostered
by CFIA at various levels facilitated the effective implementation of
the feed ban.

> III.B.1.a.5. *[Inspections and compliance]{.underline}*

Once the new feed regulations had been introduced, communications with
the affected industries broadened and CFIA implemented an inspection
program. This program was introduced in phases. From 1997-2000,
inspection activities focused on integrating the feed ban's requirements
into standard industry practices. For example, since 1998, rendering
facilities were required to pass an annual inspection in order to renew
their permits to operate. In 2000 and 2001, CFIA modified its compliance
programs by increasing the frequency of inspections of commercial feed
mills from once every three years to every year and by continuing the
annual inspection and permitting of all rendering facilities. Since
2002, CFIA has been conducting annual inspections of all rendering and
commercial feed mill facilities and some ruminant feeders and retail
feed distributors. There are approximately 20 feed mills per renderer
and 400 livestock

producers per feed mill. Because of the impact of each renderer or feed
mill on so many producers, measures implemented by CFIA to prevent
commingling or cross contamination of ruminant feed with prohibited
materials directed at the rendering and feed manufacturing industries
were essential for implementation of an effective feed ban. USDA has
concluded that, in combination with labeling and record keeping
requirements, these measures have continued to serve to prevent feeding
of prohibited protein to cattle (USDA 2005).

> III.B.1.a.6. *[On-farm feeding practices contributing to feed
> ban]{.underline}*
>
> *[efficacy]{.underline}*

To evaluate the implementation and effectiveness of the feed ban at the
farm level, it is important to consider on-farm feeding practices. Most
Canadian cattle are raised on either dairy farms or beef cattle
operations. The nutritional requirements of dairy and beef cattle
differ, and the nutritional needs of each vary by age and stage of
production. Animal source proteins may be useful in the rations of dairy
cattle to balance specific nutrients (lysine and other amino acids,
calcium, and phosphorus) and supplement protein intake. However, a
variety of plant proteins and animal protein alternatives from
non‑prohibited sources are available to Canadian producers including
fish meal, porcine blood meal, feather meal, and processed soy products.
Most cattle producers do not hold extensive long term inventories of
purchased feeds on their farms due to limited storage space and expense.
These practices make it unlikely that feeds containing prohibited
material were available for more than a few months after the original
implementation of the feed ban. The possible exception is mineral mixes
produced before the feed ban that may have contained ruminant meat and
bone meal. Mineral mixes are typically fed daily but in very small
quantities (grams rather than pounds per day) (NRC 2001; NRC 1996) and
may be stored on the farms for longer periods of time. We believe,
however, that they are not likely to have been purchased for use for
periods longer than a year.

Both beef and dairy cattle production can be considered to have an
annual or 12-month cycle, in that a cow on a beef or dairy farm will
generally give birth once a year. Calving occurs year-round on Canada's
dairy farms to ensure a constant supply of fluid milk and the farms
typically raise their own replacement heifers. Most dairy farms produce
their own forage and grains (CFIA 2002). Forages produced seasonally are
stored on the farm to provide the basis for the diet fed to dairy cattle
of all ages and production stages. Protein supplements and specialty
feeds, such as mixed calf feeds, are typically purchased commercially in
quantities to be fed out over a few months because these supplemental
feeds are expensive to purchase, costly to store, and may deteriorate
with time. Typically, purchased feeds are available throughout the year
with only moderate price variations, so there is little incentive for
producers to maintain large on-farm inventories (Leger 2005 personal
communication). The Canadian beef production cycle is very seasonal in
that cows are bred so that calving occurs at the same time of year,
general in the spring (CFIA 2002). Producers are not likely to carry
extensive feed inventories from season to season (Gow 2005 personal
communication). Therefore, in both dairy and beef production, a 12-month
period would generally be sufficient to allow purchased feed products
that may contain MBM to be completely used.

> III.B.1.b. *Conclusions: Infectivity release via importation of live
> bovines*

In its previous risk analysis (APHIS 2004), APHIS concluded that, at the
time the analysis was conducted, Canada had an effective feed ban in
place. However, that analysis did not attempt to establish a specific
date on which the ban became effective. The feed ban comprises a number
of interrelated measures that have a cumulative effect, and compliance
with these measures continues to increase as the program evolves. In
addition, since the implementation of the feed ban on August 4, 1997,
CFIA has continued to revise and strengthen its processes and procedures
to further enhance the effectiveness of the feed ban. APHIS concludes
that all of these factors have resulted in an incremental reduction in
the risk that Canadian cattle will be exposed to the BSE agent.

As discussed above, a "practical implementation period" of six months
has been estimated for the feed ban to be fully implemented, making
February 1998 a more realistic date on which the ban can be considered
to have gone into effect. The likelihood that cattle born after that
date would be exposed to the BSE agent decreases even further over time.
APHIS considers that a period of one year following the full
implementation of the feed ban allows sufficient time for the measures
taken by Canada to have their desired effect. Therefore, APHIS concludes
that cattle born on or after March 1, 1999 are unlikely to have been
exposed to the BSE agent via feed and can be imported into the United
States for any purpose with a very low risk that they will be infected
with the BSE agent.

III.B.2. [Release of BSE infectivity via blood and blood
products.]{.underline}

APHIS proposes that blood and blood products from Canadian bovines be
allowed to enter the United States under certain conditions. This
section evaluates the likelihood of introduction of BSE into the United
States via these commodities, assuming the implementation of several
required mitigations listed here. The blood and blood products must be
from a clinically normal animal and, if harvested at the time of
slaughter, the animal was not subjected to a stunning process with a
device injecting compressed air or gas into the cranial cavity or to a
pithing process. For fetal bovine serum (FBS), the mitigations are that
the dam must pass ante-mortem inspection, the uterus must be removed
from the dam's abdominal cavity intact and taken to an area separate
from the kill floor for collection. All blood must be collected in a
closed system.

Following the risk assessment format described in the Introduction, in
this section we analyze the various nodes in the potential risk pathway
for imported blood and blood products from Canada. We first provide
justification for focusing our discussion on those products used in the
production of veterinary vaccines and drugs. In keeping with the scope
of this risk assessment, we are addressing only those pathways that may
influence animal health[^8]. The impact of BSE prevalence in Canada on
the overall likelihood of release of infectivity into the United States
will be integrated with the findings of this section in the release
summary described in Section III.D.2.

> III.B.2.a. *Scope of the analysis: relevant products*

Blood and blood products can be divided into two main groups: whole
blood and cellular derivatives such as red cell concentrate, platelets,
and other cellular elements; and plasma-derived products including serum
(including FBS), clotting factors, immunoglobulins and albumin (Farshid,
et al. 2005). Plasma is the cell-free portion of the blood. Serum is
plasma with fibrinogen and clotting factors removed.

Because blood and blood products (or products manufactured with them)
are typically delivered by injection, they present different risks than
most other bovine products considered for import. Injection presents a
different risk pathway than does oral consumption of BSE-contaminated
bovine materials. The latter pathway is commonly evaluated in the cattle
BSE literature. The route of exposure can affect the risk of disease
transmission. The relative efficiencies of transmission have been
reported to be, in decreasing order, intracerebral (IC), intravenous
(IV), intraperitoneal (IP), subcutaneous/intramuscular (SC/IM), and
oral/intragastric. In mouse scrapie models, it is estimated that the
subcutaneous/intramuscular route requires 10,000 times the intracerebral
dose required to produce infection (Prince, et al. 2003). The equivalent
of 100,000 IC doses is thought to be necessary for infection by the
oral/intragastric route (Prince, et al. 2003). We extrapolate from these
data that mice exposed to scrapie via the IM or SC routes are 10 times
more likely to become infected than those exposed orally. Therefore, we
limit this assessment to the pathways in which these products can be
used in animal vaccines and injectable drugs.

Of the various products listed above, only plasma-derived fetal bovine
serum (FBS), also called fetal calf serum (FCS), and bovine serum
albumin (BSA) derived from adult and calf serum are used in significant
amounts for the preparation of animal vaccines and drugs. Other products
that could theoretically be used in the manufacture of animal drugs
include cell-derived components such as hemin, hemoglobin, lymphocytes
and platelets; and plasma-derived products, such as blood lipids, bovine
immunoglobulins, clotting factors, cytokines, fibronectin, Fractions I-V
(various proteins separated from plasma), hormones (e.g. serum
gonadotropin), iron, and plasma protein (Popek 2005 personal
communication). In practice, however, these items are not used in the
manufacture of animal vaccines and drugs, limiting their role in the
potential BSE risk pathway for animal exposure.

> III.B.2.b. *Infectivity of blood and relevant blood products*

Experiments based on primary infection by the oral route have examined
tissues from BSE-infected cattle. Although infectivity was identified in
various tissues, primarily in the central nervous system, it was not
demonstrated in a wide variety of other tissues. Specifically relevant
for this discussion is the fact that no BSE infectivity was demonstrated
in cattle blood or any tested derivatives (EC SSC 2002). This conclusion
derives from studies in which tissues from infected cattle were injected
intracerebrally (IC) and intraperitoneally (IP) into mice (the "mouse
bioassay"), or IC into cattle (the "cattle bioassay"). Mouse bioassays
were performed using buffy coat (the white cell fraction of centrifuged
whole blood), clotted blood, fetal calf blood and serum from confirmed
clinical cases (Kimberlin 1996 cited in EC SSC 2002). Mouse and cattle
bioassays were performed on buffy coat from cattle experimentally
exposed orally to the BSE agent. In all cases, no evidence of
infectivity was detected.

Because no evidence of infectivity has been found in cattle blood or the
components listed here, we could end this portion of the release
assessment at this point. However, we acknowledge that the route of
exposure -- injection vs. oral consumption -- warrants further
consideration. We also recognize that additional processing steps may
have further mitigative effects, and therefore, should be presented.
However, presenting direct evidence for the effects of processing of
bovine blood on the persistence of BSE infectivity is not possible
because infectivity is not detectable even in unprocessed bovine blood.
Thus, although APHIS generally avoids extrapolating from studies of TSEs
in other species, in order to utilize the only available evidence, we
have elected to incorporate such information here. Thus, we cautiously
use studies on TSEs in other species as potential indicators of the
behavior of BSE in cattle blood if it were to be present in previously
undetectable levels.

Investigators have demonstrated that BSE can be transmitted to sheep by
transfusion of whole blood from sheep experimentally infected with BSE
(Houston, et al. 2000; Hunter, et al. 2002). In these studies, a
transfusion of 400 ml of whole blood, taken from clinically normal
infected sheep, caused disease in 2 of 24 recipients. Blood or buffy
coat taken from clinically ill animals, however, did not cause disease
in the 4 recipients. These same investigators also examined scrapie in
sheep. A total of 4 sheep out of 21 transfused with blood from sheep
naturally infected with scrapie developed disease. The transfusion of
buffy coat derived from a clinically ill animal caused disease in the
recipient. The Scientific Steering Committee of the European Commission
examined these studies and their implications. They concluded that the
finding of infectivity in the blood of sheep could not be extrapolated
to BSE in cattle (EC SSC 2002a).

Brown, et al. (1999) using a human strain of TSE
(Gerstmann-Straussler-Scheinker, or GSS) in mice inoculated
intracerebrally, concluded that infectivity was present in the buffy
coat (platelets, white cells) during the preclinical phase of TSE, but
absent or in only trace amounts in the plasma or plasma fractions.
Following the onset of clinical signs, increased infectivity of both
buffy coat and plasma was found, but still very low compared to levels
in the central nervous system. As cited in a review of the relevant
literature (Comer 2004, p. II.18), most studies using a rodent model and
adapted strains of scrapie or CJD demonstrated that the fractions
containing white blood cells have the highest levels of infectivity.

In contrast to investigations of the natural distribution of infectivity
in rodent blood fractions, one "spiking" study added high levels of
hamster-adapted scrapie infectivity from brain homogenate to normal
human blood. Following fractionation by centrifugation into red cells,
white cells/platelets, and plasma components, titrations indicated that
the majority of infectivity was in the red cell component (Brown, et al.
1998). These results, although not as relevant to understanding the
natural distribution of TSEs in blood, may potentially apply to the
distribution following cross-contamination at blood collection.
Therefore, if contrary to current research, or if the proposed
mitigations are not properly implemented, any BSE infectivity is present
in bovine blood, either naturally or via cross-contamination, it would
likely be highest in the cellular components. These fractions, both red
and white cells, are excluded when harvesting FBS and BSA used in the
preparation of vaccines and drugs.

Further decrease in TSE infectivity occurs with fractionation of plasma
proteins. Fractionation is the process whereby specific proteins, such
as albumin, are separated out from other components of the plasma.
Infectivity in various fractions has been examined. For example, using
data from several cited studies Comer (2004) estimated that human
albumin contains 3.1x10^-5^ vCJD ID~50~/gram. Compared to Comer's
estimates of infectivity in whole blood (2 iv vCJD ID~50~/gram), this
figure represents a dramatic decrease.

In conclusion, the available evidence indicates that TSEs in other
species, when found in the blood, are localized primarily to the
cellular fractions. Although BSE has never been detected in any bovine
blood or blood product, we expect even further risk reduction after
removal of cellular fractions in the preparation of the most commonly
imported bovine blood commodities.

> III.B.2.c. *Likelihood of maternal transmission of BSE*

As discussed in Section II.A. of the Hazard Identification portion of
this document, the likelihood of maternal transmission is extremely low.
Therefore, for FBS and other fetally-derived products, maternal
transmission represents an additional risk-reduction step. If, despite
evidence to the contrary, maternal transmission of BSE were to occur,
infectivity is unlikely to localize to the fetal blood, just as it is
unlikely to localize to adult blood.

> III.B.2.d. *Proposed mitigations to prevent contamination at
> collection*

Although we have demonstrated that BSE infectivity is not likely to
localize to the adult or fetal blood, we recognize the possibility of
cross-contamination with infective tissues, or SRMs at the time of
collection, particularly in a slaughter environment. Certain
slaughterhouse stunning practices -- specifically the use of devices
that inject compressed air or gas into the cranial cavity or pithing
processes - may introduce macro-emboli of CNS tissue into the
circulatory system (Anil et al., 1999; Schmidt et al., 1999). In
addition, collection of blood in an open manner may allow other tissues
to contaminate the blood. For example, pieces of spinal cord or other
risk tissues could fall into an open container, such as a bucket or tub,
if collection and pooling of blood from several animals is done in a
slaughterhouse environment.

In order to prevent contamination due to such potential sources of
infectivity, APHIS proposes the following mitigations:

> For all blood:

1.  the blood is collected in a closed system.

> For blood collected at slaughter, the slaughtered animal:

2.  must pass ante-mortem inspection and

3.  was not subjected to a stunning process with a device injecting
    compressed air or gas into the cranial cavity, or to a pithing
    process

> For fetal bovine serum:

4.  the dam must pass ante-mortem inspection and is not subjected to a
    stunning process with a device injecting compressed air or gas into
    the cranial cavity, or to a pithing process

5.  the uterus is removed from the dam's abdominal cavity intact and
    taken to an area separate from the kill floor

> For blood collected from live donors:

6.  the donor must be free of clinical signs of disease

Based on the evidence presented above, we conclude that bovine blood is
highly unlikely to contain BSE infectivity, the fractions that are
likely to be commercially exported are highly unlikely to contain
infectivity, and that USDA-specified mitigations will prevent
cross-contamination.

III.B.3. [Release of BSE via small intestine other than distal
ileum.]{.underline}

In this section we qualitatively assess the likelihood of BSE
infectivity being introduced into the United States via the importation
from Canada of bovine small intestine other than the distal ileum. We
address this likelihood by considering the various steps, or nodes, in
the risk pathway. These nodes include the distribution of infectivity to
the small intestines, and mitigations to ensure proper removal of the
potentially infectious distal ileum.

> III.B.3.a. *Infectivity of the small intestine*

The evidence presented below demonstrates that the only portion of the
cattle intestine in which BSE infectivity has been found in any assay is
the distal ileum. We describe the most relevant observations regarding
the pathogenesis of BSE in the gastrointestinal system of cattle
experimentally and naturally exposed to the BSE agent.

-   Pivotal studies of the BSE agent include experimental investigations
    of the pathogenesis of BSE after oral exposure of cattle. The
    experimentally exposed animals received a dose of infectivity that
    was 10 to 100 times greater than most cattle that have been
    naturally exposed via contaminated feed. In these studies,
    investigators examined the distribution of the agent in the
    lymphoreticular system, the peripheral nervous system, the central
    nervous system, striated muscles, and major viscera at various times
    after exposure (Wells, et al. 1996). Infectivity in bovine tissues
    was first assayed in the mouse bioassay, a procedure in which the
    agent is injected intracerebrally and intraperitoneally into certain
    nontransgenic strains of mice (Wells, et al. 1996; 1998) which are
    then observed for development of clinical signs. Results from the
    mouse bioassay demonstrated infectivity in the distal ileum of
    cattle from 6 to 18 months and from 36 to 40 months after oral
    exposure. No infectivity was detected at any time in the esophagus,
    reticulum, rumen, abomasum, proximal small intestine, proximal
    colon, distal colon, and rectum (EC SSC 2002b). In later studies,
    the same tissues were assayed for infectivity by intracerebral
    inoculation of cattle, a more sensitivity assay method (EC SSC
    2002b). The cattle bioassay confirmed that the agent could be
    recovered only from distal ileum at times previously reported in the
    mouse bioassay.

-   Studies examining the distribution of PrP^Sc^ by
    immunohistochemistry[^9] in the distal ileum of infected cattle
    confirmed that PrP^Sc^ accumulated in Peyer's patches of the distal
    ileum at 6, 10, 14, 18, 36, and 40 months after exposure (Terry, et
    al. 2003). These findings were consistent with results from the
    mouse bioassay.

-   No PrP^Sc^ was detected by immunostaining in the duodenum, jejunum,
    cecum, colon, myenteric plexus, and submucosal plexus of calves
    orally exposed to large doses of the BSE agent and killed 6 months
    after exposure (Terry, et al. 2003). In contrast, immunostaining of
    follicles from Peyer's patches of the distal ileum did reveal the
    presence of PrP^Sc^ in these same calves.

-   The distal ilea of 29 naturally occurring cases of BSE were examined
    for PrP by immunohistochemistry. Sparse PrP^Sc^-specific
    immunostaining was observed in neurons of the myenteric plexus of
    the distal ileum of nine of the cattle. No immunostaining in the
    submucosal plexus of the distal ileum of any of the infected cattle
    was observed, suggesting a very low level of infectivity in the
    enteric nervous system in the clinical phase of BSE (Terry, et al.
    2003).

In summary, BSE infectivity has been found in the distal ileum of
experimentally exposed cattle and not in other sections of the
intestine. In addition, in naturally occurring cases, sparse
immunostaining has been observed in the myenteric plexus of the distal
ileum. Since the myenteric plexus extends throughout the small
intestine, we acknowledge the possibility that infectivity might exist
in the myenteric plexus of the jejunum or the duodenum. However, if
infectivity in intestinal tissues (other than distal ileum) exists, it
is below the level of detection by both the mouse and cattle bioassay.
Given the relative efficacies of these experimental modes of
transmission compared to oral exposure at doses estimated to have
occurred in the field, we conclude that intestine other than the distal
ileum is highly unlikely to contain epidemiologically-significant levels
of infectivity, if any infectivity is present at all.

> III.B.3.b. *Likelihood of improper removal of the distal ileum*

As discussed above, the distal ileum is the only portion of the bovine
intestine in which BSE infectivity has been found in experimentally and
naturally infected cattle. Although infectivity has not been detected in
the rest of the small intestine, the complete removal of the distal
ileum is essential to ensure that imported bovine intestine does not
include a potential source of BSE infectivity. In this section we
describe the anatomic relationships between the relevant parts of the
bovine intestine and the mitigations designed to prevent inadvertent
contamination of otherwise BSE-free tissues.

> III.B.3.b.1. *[Relevant anatomy of bovine small
> intestine]{.underline}*

The small intestine of cattle attaches at its most proximal end (closest
to the mouth) to the most distal (closest to the anus) chamber of the
ruminant stomach. This most proximal segment of the small intestine is
the duodenum. Distal to the duodenum is the very long jejunum. According
to the North American Natural Casings Association, the duodenum and
jejunum are used for natural beef casings (NANCA 2004). Distal to the
jejunum is the ileum, which is estimated to be two to three feet long
(NANCA 2004). The distal-most portion of the ileum, or "distal ileum,"
is estimated to be 12 to 18 inches long. It attaches to the most
proximal portion of the large intestine, the cecum, at what is termed
the "ileocecal junction" or "ileocecal orifice." Just distal to the
ileocecal junction is the cecocolic junction.

> III.B.3.b.2. *[Mitigations to exclude distal ileum from imported
> small]{.underline}*
>
> *[intestine]{.underline}*

Since the distal ileum is the only portion of the small intestine
demonstrated to contain BSE infectivity, its exclusion would remove any
associated infectivity from the rest of the small intestine. In this
section, we discuss the mitigations required to adequately remove the
distal ileum.

USDA Food Safety Inspection Service (FSIS) and HHS Food and Drug
Administration (FDA) have determined that the distal ileum can be
effectively removed from the rest of the small intestine. They have also
determined that the remaining small intestine can be used as human food
if the distal ileum is removed (FSIS 2005, FDA 2005). To ensure the
complete removal of the distal ileum, both FSIS and FDA require the
removal of at least 80 inches of the uncoiled and trimmed small
intestine as measured from the cecocolic junction (FSIS 2005, FDA 2005).
Their regulations also allow for the facility to submit an equivalent
process to the respective agency for approval. Based on the description
of bovine intestinal anatomy, above, we concur that removal of this
tissue will exclude the distal ileum.

An authorized veterinary official of the Government of Canada will be
required to certify that any product containing bovine small intestine
does not include distal ileum as defined above. This certification will
ensure that conditions in Canada meet the standards that USDA considers
appropriate for safe trade in this commodity.

> III.B.3.c. *Conclusions: Infectivity release via importation of*
>
> *bovine intestines*

The studies described above demonstrate that the distal ileum, but not
the remainder of the bovine intestine, is a potential source of BSE
infectivity. The distal ileum is the only portion of the bovine
intestine for which OIE recommends any trade restrictions because of BSE
(OIE 2006a). Similarly, both the Food and Drug Administration (FDA 2005)
and the FSIS (FSIS 2005) have concluded that if the distal ileum is
removed from the small intestine of cattle, the remainder of the small
intestine can be used for human food.

Because bovine intestinal tissue, excluding the distal ileum, has not
been shown to contain infectious levels of the BSE agent, even if
derived from infected cattle, and because the distal ileum can be
removed at slaughter in a manner to avoid contamination, APHIS concludes
that it is highly unlikely that any BSE infectivity would be released
into the United States via bovine intestines imported from Canada.

III.C. *Projections and composition of cattle imports from Canada under
the proposed*

*rule*

Projections of cattle imports from Canada under the proposed rule,
prepared by USDA's Economic Research Service (ERS), are based on
forecasts of Canada's annual cattle inventories multiplied by the share
of inventory expected to be imported by the United States. ERS has
forecasted the percentage of cattle that would be imported, by purpose
(immediate slaughter, feeding for slaughter, and breeding), and gender,
based for the most part on data from 1992 through May 2003. The cattle
categories and import percentages, shown in Table 4, are discussed here
briefly.

  -------------------- ----------------------------- --------------------------- -----------------------
  **Table 4. Projected                                                           
  percentages of                                                                 
  cattle imports from                                                            
  Canada with the                                                                
  proposed rule**                                                                

                                                                                 

                                                     [Percentages]{.underline}   

                                                     [Sub-group]{.underline}     [Overall]{.underline}

                                                                                 

  Slaughter cattle                                                               82

                       Steers/heifers\*              53.2                        

                       Cows                          21.1                        

                       Bulls and stags               3.9                         

                       Calves\*                      3.7                         

                                                                                 

  Stockers/feeders\*                                                             13.8

                                                                                 

  Breeding cattle                                                                4.2

                       Dairy heifers/cows\*          3.6                         

                       Beef heifers/cows\*           0.4                         

                       Bulls\*                       0.2                         

                                                                                 

  Total                                                                          100
  -------------------- ----------------------------- --------------------------- -----------------------

\*As described in the following paragraphs, most of the animals in these
categories would be less than 2 years of age at the time of import.

# III.C.1. [Slaughter Cattle]{.underline}

Slaughter cattle, which would comprise up to 82 percent of the cattle
imported, are slaughtered almost immediately after crossing the border.
They are expected to have a somewhat older age distribution for the
first year that the rule would be in effect (we assume for this analysis
that this will occur in 2007), with most of the surplus inventory
eliminated by year end.

Slaughter cattle can be categorized into 1) steers[^10] and
heifers[^11]; 2) cows, bulls and stags[^12]; and 3) calves[^13] (ERS
2004; Purdue 2006). Steers and heifers are the largest category, and
would comprise about 53 percent of imports. In both the United States
and Canada, slaughter steers and heifers are generally on feed from 120
days to more than 200 days before slaughter. Most of them are between 16
and 24 months of age at slaughter, with some over 26 months. Because
more females than males are kept in the population for breeding
(Matthews and Short 2001), we expect approximately 60 percent of this
sub-group of slaughter cattle to be steers and 40 percent to be heifers.
Historically, the percentage of steers has ranged from 53 to 65 percent,
depending on the level of heifer retention for the Canadian breeding
herd.

Slaughter cows are expected to comprise roughly 21 percent of imports.
Approximately 60 percent of these would be dairy cows. Their median age
would be approximately 3.8 years, with most between 3 and 6 years of
age. Slaughter beef cows would average 6 years of age, with most between
5 and 7 years of age.

Slaughter bulls and stags are past breeding service and would comprise
less than 4 percent of imports. Most are 5 to 7 years of age, with a
median age of approximately 5.5 years.

Vealers and light calves would also comprise less than 4 percent of
imports. They include cattle from less than 1 month old up to 8 months,
with most between 4 and 5 months of age.

# III.C.2. [Feeders/stockers]{.underline}

Weaned steers and heifers (about 9 months of age) and yearlings (mostly
12 to 15 months of age) imported for feeding constitute the second
largest group after slaughter cattle, about 14 percent of the overall
total. This category is also the most variable, having ranged from 3
percent to 46 percent of Canadian cattle imports. The wide range is due
to varying weather/forage conditions, feed costs, and inventory changes
reflecting the cattle cycle. These cattle are all destined for feedlot
finishing and slaughter, but may be placed on pasture for several months
of gain before feedlot placement. They are generally placed on feed for
120 to over 200 days before being slaughtered.

III.C.3. [Breeding cattle]{.underline}

Breeding animals would comprise approximately 4 percent of imports. They
are destined for dairy and beef breeding herds and would be eventually
culled like their U.S. herd mates. Dairy heifers and cows constitute the
largest share of breeding cattle. They are mostly bred (pregnant)
heifers that are 15 to 19 months of age and due to calve. They enter the
milking herd at about 24 to 26 months of age. Young, open (not pregnant)
dairy heifers and a small number of cows that have calved complete this
category.

Beef heifers and cows would comprise less than 1 percent of imports and,
like the dairy breeding stock, would include open and bred heifers and
cows.

Bulls for breeding would constitute a very small proportion of total
imports. This category includes beef bulls 15 to 24 months of age, as
well as a few dairy bulls.

ERS has estimated the total projected number of animals to be imported
for 2007 (the year in which we anticipate implementing the rule) through
2026 to provide twenty years of input data to be incorporated into the
exposure model informing the exposure assessment below. These total
annual projections are broken out into the various use categories in
Table 5 below.

**Table 5. Projected imports of various cattle use types for years 2007
through 2026.**

  ------------- ----------- -------- ---------- ------------- ------------- ------ ------- --------- ------- ------------ --------- ---- ------- ------- --------------
  **CASE:                                                                                                                                                
  shares based                                                                                                                                           
  on sum of                                                                                                                                              
  annual                                                                                                                                                 
  imports over                                                                                                                                           
  1992-2003**                                                                                                                                            

                                                                                                                                                         

                                                **Projected                                                                                              
                                                cattle                                                                                                   
                                                imports to US                                                                                            
                                                from Canada,                                                                                             
                                                by category                                                                                              
                                                \-- 1,000                                                                                                
                                                head**                                                                                                   

                Canadian                        U.S.          **SLAUGHTER                                    **BREEDING                                  **Stocker/**
                                                              CATTLE**                                       CATTLE**                                    

                Inventory   Pct      Pct                      Steers &      Cows   Bulls   Vealers / Sub-    Dairy cows   Beef cows      Bulls   Sub-    **feeders**

  YEAR          ,000 hd.    change   exported   ,000 hd.      heifers              & stags Light     total   / heifers    / heifers              total   (male+fem)
                                                                                           calves                                                        

                                                                                                                                                         

  2007          14,400      97.1     9.5        1,368         728           289    54      51        1,121   50           5              3       58      189

  2008          14,050      97.6     9.0        1,265         673           267    50      47        1,036   46           5              3       53      175

  2009          14,250      101.4    8.5        1,211         644           255    48      45        993     44           4              3       51      167

  2010          14,300      100.4    9.0        1,287         685           271    50      48        1,055   47           5              3       54      178

  2011          14,375      100.5    9.0        1,294         688           273    51      49        1,060   47           5              3       54      179

  2012          14,450      100.5    9.0        1,301         692           274    51      49        1,066   47           5              3       55      180

  2013          14,550      100.7    9.0        1,310         697           276    51      49        1,073   47           5              3       55      181

  2014          14,650      100.7    9.0        1,319         701           278    52      49        1,081   48           5              3       55      182

  2015          14,250      97.3     9.5        1,354         720           286    53      51        1,110   49           5              3       57      187

  2016          14,100      98.9     9.5        1,340         713           283    53      50        1,098   49           5              3       56      185

  2017          14,425      102.3    9.0        1,298         691           274    51      49        1,064   47           5              3       55      179

  2018          14,500      100.5    9.0        1,305         694           275    51      49        1,070   47           5              3       55      180

  2019          14,650      101.0    9.0        1,319         701           278    52      49        1,081   48           5              3       55      182

  2020          14,875      101.5    9.0        1,339         712           282    53      50        1,097   49           5              3       56      185

  2021          15,200      102.2    9.0        1,368         728           289    54      51        1,121   50           5              3       58      189

  2022          15,350      101.0    8.5        1,305         694           275    51      49        1,069   47           5              3       55      180

  2023          15,450      100.7    8.5        1,313         699           277    52      49        1,076   48           5              3       55      182

  2024          15,650      101.3    8.0        1,252         666           264    49      47        1,026   45           4              3       53      173

  2025          16,000      102.2    8.0        1,280         681           270    50      48        1,049   46           5              3       54      177

  2026          16,000      100.0    8.5        1,360         724           287    53      51        1,115   49           5              3       57      188
  ------------- ----------- -------- ---------- ------------- ------------- ------ ------- --------- ------- ------------ --------- ---- ------- ------- --------------

**Source: Expert opinion, USDA Economic Research Service, Market and
Trade Economics Division, Animal Products, Grains, and Oil Seeds Branch.
Based on "USDA Agricultural Baseline Projections to 2015," United States
Department of Agriculture, Interagency Agricultural Projections
Committee, Baseline Report OCE-2006-1, February 2006,
<http://www.usda.gov/oce/commodity/ag_baseline.htm>; and import data
1992-2003; and projected Canadian inventory.**

III.C. 4. [Projected bison imports]{.underline}

**[Table 6. Projected Bison Imports]{.underline}**

  ----------- ------------------- ----------- ------------- -----------------
  Projected                                                 
  Bison                                                     
  Imports to                                                
  United                                                    
  States from                                               
  Canada by                                                 
  Usage                                                     
  Category                                                  

                                                            

  YEAR        Canadian Bison      Slaughter   Breeding      Stocker/Feeders
              Exports to United                             
              States                                        

                                                             

  2007        4,000               2,500       250           1250

  2008        3,150               2,400       250           500

  2009-2026   2,500               2,000       250           250
  ----------- ------------------- ----------- ------------- -----------------

**Source: ERS Market and Trade Economics Division, Animal Products
Branch.**

Based on Department of Commerce, Bureau of the Census import data from
1996-2002, the ERS Market and Trade Economics Division, Animal Products
Branch estimated the composition of projected bison imports. Because of
restrictions on the movement of bison from Canada into the United
States, they anticipate a higher number of exports in 2007 and 2008 than
for subsequent years. From 2009, approximately 2500 bison are projected
to be imported per year, with the following breakdown across three usage
types. The numbers per usage type per year are presented in Table 6 and
the overall breakdowns are described below:

# Slaughter Bison

The primary share of the imports, 80 percent, is likely to be for
immediate slaughter. About 80 percent of these imports are male, 5
percent female and about 15 percent unknown.

# Breeding Bison

Of the 2500 bison expected to be imported per year, approximately 10
percent are for breeding purposes. Roughly 70 percent of these animals
are female and 30 percent male. These imports provide a source of
genetic diversity to the U.S. bison herd.

# Feeder Bison

Feeders comprise about 10 percent of imports, of which roughly 90 to 95
percent are male.

III.D. *Release conclusions*

In the preceding sections of the release assessment, we have presented
several pieces of evidence that together indicate that, even when making
risk-inflating assumptions, very little BSE infectivity is expected to
be released into the United States via the proposed additional
commodities imported from Canada. In this final portion of the release
assessment, we integrate the findings of these various sections.

III.D.1. [Likelihood of BSE release via import of live
bovines]{.underline}

In section III.A., we present results of a modified, previously
published model (BSurvE) that estimates the BSE prevalence in Canada's
standing (August 2006) cattle population. Because of uncertainty in
various parameters and constraints of the model itself, it incorporates
some important simplifying assumptions that over-estimate the prevalence
values. For example, the positive test result from the case of Canadian
origin that was diagnosed in the United States was included among the
positive surveillance results (numerator), whereas negative and
clinically normal animals of Canadian origin exported to the United
States were not included in the population total (denominator). This
admittedly biased approach inflates the Canadian prevalence estimates.

We assess the likelihood of release of BSE infectivity over an extended
period of time, assuming that the proposed rule would apply into the
foreseeable future. In order to allow sufficient time for several
potential amplification cycles (roughly 5-7 years each), we have
evaluated release over a 20 year period: 2007-2026. We considered
different scenarios for release, providing both qualitative and
quantitative inputs to inform the exposure assessment.

In section III.B.1, we discuss the proposed mitigation of limiting
animals intended for import to those born after the date the feed ban
was effectively enforced. The evidence presented about the feed ban and
related activities in Canada support the conclusion that cattle born in
Canada on or after March 1, 1999, will have a very low risk that they
have been exposed to the BSE agent. This conclusion contributes to the
qualitative inputs evaluated in the exposure assessment. As further
described below, however, data limitations prevent quantitative
consideration of this mitigation.

As noted previously, our prevalence estimates are for the standing
cattle population in August 2006. As described in Section III.A.,
implementation of a ruminant feed ban results in decreasing BSE
prevalence over time (DEFRA 2006, EC 2005a; Cohen, et al. 2001; 2003;
Cohen and Gray 2005). The methods we use to estimate prevalence,
however, cannot project the changes expected over the 20-year period of
our analysis. Therefore, we infer that the BSE prevalence and subsequent
release of infectivity from Canada for each of the 20 years after the
anticipated implementation of the proposed rule (estimated as 2007) are
less than expressed by our quantitative estimate. We use these
prevalence estimates in the exposure assessment in two different ways.
First, we use them to provide a current estimate of possible release via
live animal imports in the first year of our analysis, and then we
qualitatively consider the most likely scenario of decreasing prevalence
over subsequent years. Second, as we allow for less likely outcomes, we
use these prevalence estimates as risk-inflating numeric surrogates for
the release input parameter of the exposure model (Attachment 2) used to
inform our exposure assessment.

Using the methods described in Section III.A., we have two estimates of
expected (mean) prevalence in the Canadian herd for August 2006. One
estimate (BSurvE), based on the accumulated Canadian BSE surveillance
data, expresses the expected prevalence as 3.9\*10^-6^ infected cattle.
When combined with import projections for 2007 from Table 5 in Section
III.C., this estimate predicts that less than 6 of the over 1.3 million
imported animals will be infected (Table 7). This value is higher than
that for nearly all other years in the analysis because, as seen in
Table 5, 2007 is a year in which a relatively large number of animals is
projected to be imported. Therefore, the values for 2007 reflect the
highest number of "expected" infected animals.

The other estimate (BBC) of the August 2006 BSE prevalence in Canada
incorporates both prior surveillance data and evidence from the UK on
the impact of a feed ban. Given that Canada has an effective feed ban,
as described in Section III.B.1., this estimate is likely the more
realistic. Moreover, since imported live bovines from Canada must be
born after the date of effective implementation of the feed ban, this
lower estimate (expected value=6.8\*10^-7^) is far more applicable to
the current proposal. Using this approach, as indicated in Table 7, we
"expect" roughly 0.94 infected animals in that year. Once again, this
prediction is for 2007, a year in which our import projections predict
higher volumes, and therefore compared to the subsequent 19 years,
represents the highest number for this prevalence estimate.

Furthermore, the two prevalence estimates are calculated for the total
cattle population in Canada, including cattle born before the date which
APHIS concludes that the feed ban was effectively enforced. Because of
data limitations, we did not calculate the prevalence by birth cohorts.
Epidemiological evidence in the UK suggests that cohorts born after
effective implementation of the feed ban are much less likely to develop
disease than cohorts born before the effective implementation of such a
ban (DEFRA 2006). Therefore, Canadian cattle born after the date the
feed ban was effectively enforced are much less likely to be exposed to
infective material and become infected with BSE. This evidence is
considered in the qualitative evaluation of the most likely scenario in
which prevalence in Canada decreases over the next 20 years. However,
this evidence is not considered in the less likely scenarios represented
in the quantitative analysis. In those scenarios, we assume that all
animals are equally likely to have been exposed to infective material
and that the prevalence remains constant over the next 20 years.

As noted in the import projections, the majority of imports are expected
to be less than two years of age at the time of import. Therefore, in
2007, this large group of younger animals would be born many years after
both the initial implementation of the feed ban, and the date at which
we consider the ban to have been effectively enforced. In subsequent
years, these animals would be born an increasingly longer time after
those dates. Therefore, they would be even less likely to have been
exposed to infected feed. Like the evidence described in the preceding
paragraph, this information is considered in the qualitative
evaluations, but not in the quantitative evaluations.

Table 7 below presents projected percentages, total (number) and
infected cattle imports by usage type from Canada for 2007, based on
estimates of August 2006 prevalence. These values are presented not as
estimates of predicted release, but to reasonably inform the
quantitative exposure simulations in Section IV of this document.

**Table 7. Projected percentages, total (number), and infected cattle
imports by usage type from Canada for 2007. The two prevalence estimates
reflect the two methods used in Section III.A.**

  ------------------ ------------------------------- --------------------------- ----------- ----------------- -----------------
                     **[Percentages]{.underline}**                               **Number    **Number infected 
                                                                                 imported    2007**            
                                                                                 2007**                        

                     **[Sub-group]{.underline}**     **[Overall]{.underline}**               **Prevalence=**   **Prevalence=**

                                                                                             **6.8\*10\^-7**   **3.9\*10\^-6**

                                                                                                               

  Slaughter cattle                                   82                          1,121,000   0.76              4.37

  Steers/heifers     53.2                                                        728,000     0.50              2.84

  Cows               21.1                                                        289,000     0.20              1.13

  Bulls and stags    3.9                                                         54,000      0.04              0.21

  Calves             3.7                                                         51,000      0.03              0.20

  Stockers/feeders                                   13.8                        196,000     0.13              0.76

  Breeding cattle                                    4.2                         60,000      0.04              0.23

  Dairy heifers/cows 3.6                                                         51,000      0.03              0.20

  Beef heifers/cows  0.4                                                         5,000       0.00              0.02

  Bulls              0.2                                                         3,000       0.00              0.01

                                                                                                               

  Total              100                             100                                     0.94              5.37
  ------------------ ------------------------------- --------------------------- ----------- ----------------- -----------------

> III.D.1.a. *Release of BSE infectivity via import of live bison*

Although the bulk of the live bovines expected to enter the United
States following implementation of the proposed rule would be cattle, we
also expect the entry of some bison. These animals will also be required
to be born after the date of the effective feed ban. As reported in
Section III.C., except for the first two years, we expect approximately
2,500 bison to enter annually. In the absence of evidence to the
contrary, we assume that the prevalence of BSE in bison is the same as
that in cattle. Since no cases have been reported in North American
bison, this assumption likely overestimates the risk associated with
importation of this species. Nonetheless, even when assuming that bison
are as likely as cattle to be infected with BSE, and when using August
2006 BSE prevalence estimates, we would expect only 0.0098 infected
bison imported annually, or one in 103 years, when not considering the
additional evidence of the expected impact of a feed ban, currently, or
in the future. Even for 2007, the year in which the greatest number of
bison exports is expected (4000), we calculate only 0.0156 infected
bison to be imported.

Given that the feed ban applies to all ruminants, including bison, we
expect that it has reduced the prevalence in that population as much as
it has in cattle. When incorporating the additional evidence from the UK
on the expected impact of a feed ban into the August 2006 prevalence
estimate, and assuming 2500 animals imported per year, the "expected"
number of infected bison drops to 0.0017 per year, or one in 588 years,
even when assuming no subsequent drop in prevalence over that period.
Given the essentially negligible rate at which we might, even with
cautious assumptions, introduce BSE infectivity via bison, we have
elected not to analyze this pathway further.

> III.D.2. [Release of BSE infectivity via import of blood and blood
> products]{.underline}

As demonstrated in Sections III.A. and III.B.2., multiple steps in the
risk pathway act as safeguards against the release of BSE infectivity
from Canada into the United States via imported blood and blood
products. First, as described in Section III.A., the underlying BSE
prevalence in Canada is now extremely low (less than 7 per 10 million
cattle under the BBC model, or less than 4 per million under BSurvE
Prevalence B), and is expected to decrease further. Therefore, the
chance of collecting blood from an infected animal is very small. Even
if one of the very few infected animals were a source of imported blood
or blood products, several steps, or nodes, in the risk pathway act to
further diminish the likelihood of release. The first of these is the
evidence that, even in infected animals, BSE infectivity has not been
detected in the blood of cattle. Furthermore, the most commonly imported
blood-derived commodity, fetal bovine serum, passes through two
additional risk-reducing nodes: the very low likelihood of maternal
transmission and, once again, the evidence that BSE does not localize to
bovine (in this case, fetal) blood.

Additional nodes that apply to both adult- and fetal-derived blood
reflect the continued drop in likelihood attributable to blood
fractionation. Specifically, even in those species in which any TSE
infectivity has been found in whole blood, it is typically at a much
lower level in the plasma or serum from which the vast majority of
blood-derived commodities are derived. Therefore, even if bovines were
to have some infectivity in their blood, it would not persist in the
significantly traded commodities (e.g., FBS and BSA).

The pathways described in the previous paragraphs reflect a series of
sequential, and hence, multiplicative nodes. The likelihood of
infectivity being released directly (not secondary to
cross-contamination) via imported blood and blood products is the
conceptual product of the likelihoods of each node contained within the
pathway. Thus, the product of each of these very low likelihoods
reflects essentially negligible risk.

> III.D.2.a. *Likelihood of cross-contamination at slaughter*

The possibility of cross-contamination at slaughter of bovine blood with
infectivity from high risk tissues is an additional potential risk
pathway that must be considered. Because this pathway is separate, in
part, from the one described above, its effects are additive.
Cross-contamination could potentially occur if, during slaughter or
processing, collected blood were contaminated with specified risk
materials (SRMs). Like the pathway described in the preceding paragraph,
the cross-contamination pathway would also be greatly reduced by the
very low prevalence of BSE in Canada. However, the cross-contamination
risk pathway could bypass the sequential safeguards described above.
Existing prohibitions on compressed air stunning will prevent the
creation of brain tissue emboli that could potentially contaminate the
blood (CFIA 2006a). In order to further minimize the likelihood of
release associated with this pathway, we are proposing mitigations that
will effectively prevent cross-contamination during the collection
process. Specifically, the slaughtered animal (in some cases, the dam of
the animal from which the fetal blood is collected) must pass antemortem
inspection, the uterus must be removed intact and taken to a separate
area, and blood (both fetal and non-fetal) must be collected in a closed
system.

Based on the evidence and the proposed mitigations described in this
document, we conclude that there is a negligible likelihood of
additional BSE infectivity being introduced into the United States via
blood and blood products imported from Canada.

III.D.3. [Release of BSE infectivity via import of small intestines
other than distal]{.underline}

[ileum]{.underline}

As for the two groups of commodities described above, live animals and
blood and blood products, the likelihood of release of infectivity via
imported small intestine from Canada is reduced in large part by the
very low BSE prevalence demonstrated in Section III.A. Based on the
discussions in Sections III.A. and in the introduction to this release
summary, we conclude that the current prevalence in Canada will decrease
further. If, despite this presumably decreasing prevalence, an infected
animal were slaughtered, two additional risk pathway nodes further
reduce the likelihood of BSE release via the import of bovine small
intestine other than the distal ileum.

The first of these nodes is the likelihood that BSE infectivity would be
present in the small intestine, other than the distal ileum. Section
III.B.3. presents abundant evidence that such a likelihood is
exceedingly small. In essence, all research indicates that when BSE is
localized to the small intestine, it is detected only in the distal
ileum. All other portions are considered to be free of infectious levels
of the agent.

The second node, in parallel, and thus additive in nature to the first,
addresses the exclusion of the potentially infectious distal ileum. In
Section II.B.3., we discuss the mitigations which require the removal of
this SRM. FSIS and FDA have determined that the distal ileum can be
effectively removed by discarding the most distal 80 inches of the
uncoiled and trimmed small intestine. Their conclusions are supported by
anatomic evidence that the bovine ileum is only two to three feet long
(NANCA 2004). Moreover, FDA and FSIS both conclude that small intestine
from which the distal ileum has been so removed can be used for human
consumption. An authorized veterinary official of the government of
Canada will be required to certify that any product containing bovine
small intestine adheres to these requirements.

Therefore, the two crucial nodes in the potential risk pathway
associated with importation of small intestine other than distal ileum
that reduce the likelihood of infectivity are the absence of infectivity
in these tissues, and mitigations to ensure adequate removal of
potentially infective distal ileum. Based on the presented evidence, we
conclude that the likelihood of introducing BSE infectivity in bovine
small intestine other than distal ileum imported from Canada is
negligible.

> III.D.4. [Release conclusions]{.underline}

In summary, based on the evidence and proposed mitigations discussed in
the release assessment, we conclude that the likelihood of releasing BSE
into the United States from Canada via importation of live bovines,
blood and blood products or intestines is extremely low. The numeric
estimates presented above are used as inputs for the exposure model
discussed in the next section of the document, and do not in themselves
represent our expectation of release.

IV. **Exposure Assessment**

IV\. A. *Live Bovines*

This section of the risk assessment evaluates the pathways by which
infected Canadian cattle, if imported, might expose U.S. cattle to BSE,
and the likelihood that these pathways might lead to the establishment
of the disease in the U.S. cattle population. The nature and likelihood
of these pathways depend in large part on mitigations acting in series
and in parallel which reduce the likelihood that BSE will be established
in the United States.

As demonstrated in the release assessment, we conclude that the
prevalence of BSE among Canadian cattle is extremely low. The models
which we used to evaluate prevalence produce two estimates of prevalence
for August 2006: one that does not include additional evidence from the
UK on the expected impact of a feed ban (BSurvE Prevalance B), and one
that does (BBC). We maintain that the latter estimate is more
appropriate for this risk assessment because the proposed mitigation
requiring that all imported live bovines are born on or after March 1,
1999, means that these animals are subject to the implemented feed ban.
In order to determine the significance of this assertion, we include the
higher prevalence estimate in the sensitivity analysis discussed below.

As described in Section III.A.2.a of the Release assessment, empirical
observation and simulation studies document a continued drop in
prevalence following implementation of a feed ban. Because the rate at
which this drop may occur in Canada cannot be adequately quantified, we
assume for the purposes of performing a quantitative analysis that
prevalence (and thus the likelihood of release) will remain constant
over the 20 years of the analysis (2007-2026). Therefore, the numeric
outputs presented in this section reflect this highly cautious
assumption. Our interpretation of these results, however, is further
informed by evidence that the prevalence will decrease over this time
period.

IV.A.1. [Pathway Analysis: Barriers to BSE transmission and
amplification]{.underline}

If an infected animal were to be imported, then each of the remaining
barriers outlined here reduces the level of infectivity in the system.
For an infected imported Canadian animal to transmit infection to a U.S.
cow, four sets of barriers must be crossed:

1.  Slaughter controls and dead animal disposal

2.  Rendering inactivation

3.  Feed manufacturing and use controls

4.  Biologic limitations to susceptibility

Current FSIS slaughter restrictions in the United States decrease the
likelihood that any infectious raw materials from an infected imported
animal will be incorporated into the human or animal food supply. These
restrictions include antemortem inspections, which reduce the amount of
infectivity that could pass into the rendering process. BSE-infected
cattle in the end-stages of infection, and containing the greatest
amount of infectivity, will typically present with central nervous
system signs or as downer cattle and will be condemned. Prohibiting the
slaughter of downer cattle and those otherwise displaying clinical signs
recognized as consistent with BSE infection, explicitly eliminates the
potential for their infectivity reaching humans. Such a condemnation
will also trigger a diagnostic investigation of the suspect animal,
including a test for BSE. If positive, its infectivity will be
inactivated by incineration. Also, without slaughter as an option for
handling downer cattle, some farmers and ranchers may dispose of such
cattle on their premises, thereby eliminating these cattle as a source
of infectivity in cattle feed.

The FDA's 1997 ruminant feed ban, found in Title 21 of the *Code of
Federal Regulations* Part 589.2000 (FDA 2006) regulates rendering, feed
manufacture and use of prohibited feeds to reduce the risk of BSE
recycling in the United States. Rendering processes in the United States
will inactivate significant levels of the agent, further reducing the
level of infectivity in prohibited bovine MBM. These processes
inactivate much of any potentially remaining infectivity by subjecting
the material to intense heat and pressure. Furthermore, federal
regulations require that bovine material sent to a rendering facility
must be kept separately from low risk material and must be correctly
labeled for use by feed processors. These requirements reduce the
likelihood of cross-contamination and mislabeling by renderers.

If a fraction of the hypothetical BSE infectivity were to escape
destruction at the rendering facility, it would need to by-pass controls
imposed to prevent cross-contamination and ensure proper labeling of
rendered materials (at the renderer) and feeds produced using prohibited
MBM (at the feed mill). The controls preventing cross-contamination and
mislabeling act in parallel to one another and are additive in their
risk reduction effects. Proper separation of infectivity by prevention
of cross-contamination and mislabeling, act in series with risk
reduction steps occurring up to and including rendering. Therefore,
controls preventing cross-contamination and mislabeling are
multiplicative with these earlier steps in their risk-reduction effects.

The likelihood of exposure to any infectivity remaining in properly
manufactured and labeled, but prohibited feed, is reduced by the ban on
misfeeding of these feeds to ruminants. However, even if some remaining
infectivity were fed to cattle, in order for disease transmission to
occur, an individual animal must consume a dose high enough to be
infectious given that animal's age-specific susceptibility distribution.
In other words, the amount of infectivity present must be adequate to
infect an animal ingesting that feed. If the dose is too low, exposure
will likely not result in infection. Epidemiological and simulation
studies indicate that animals are most susceptible before 4 months of
age (Wilesmith, et al. 1988; 1992; 1992a; Ferguson, et al. 1997; De
Koeijer, et al. 2004).

Moreover, in the extremely unlikely event that an animal should become
infected from contaminated feed, it is unlikely that infectious levels
of the agent from that animal would be transmitted to other cattle
because infectivity from that animal must also circumvent all of the
barriers discussed.

IV.A.2. [Quantitative evaluation of BSE exposure and spread in the
United States]{.underline}

APHIS has arranged for the primary author of the Harvard BSE model to
simulate the impact of the mitigations described above on the likelihood
of exposure, establishment and spread of the BSE agent in the United
States following the release of infectivity in live animals imported
from Canada (see Attachment 2). Therefore, the current BSE simulation
model is a revision of one developed jointly at Tuskegee University and
at the Harvard Center for Risk Analysis (Cohen, et al. 2001; 2003).

> IV.A.2.a. *Methodology*

Historically, the Harvard BSE model (Cohen, et al. 2001; 2003) has been
used to evaluate the impact of various alternatives scenarios and risk
management options on the possible spread of BSE within the U.S. cattle
herd and the potential for human exposure to the BSE agent. The model
simulates what might happen if BSE were introduced into the U.S. cattle
population. In doing so, the model estimates whether BSE would develop
into a self-sustaining epidemic if it were introduced into the United
States, or if its prevalence would tend to decrease over time, leading
eventually to its eradication. Our use of the model focuses on the
dynamics of the disease in cattle, rather than possible human exposure.

The probability that BSE could be perpetuated in the U.S. cattle
population depends on the average number of new cases of disease that
result from each existing case. This value, designated R~0~, is referred
to as the epidemic's basic reproduction rate (Anderson 1991). If R~0~
exceeds unity (one), the disease will tend to spread. Conversely, if
R~0~ is less than unity, the number of cases will tend to decline over
time, and ultimately the disease will die out.

Previous versions and updates reflecting new domestic regulations
include parameters likely to influence the predicted spread of the
disease. Briefly, these input parameters address:

-   Dynamics of U.S. cattle population

-   BSE related mitigations during slaughter, rendering and feed
    production and usage

-   The degree of compliance with restrictions on animal slaughter,
    rendering and feed practices

-   The amount of infectivity being carried by an infected animal in
    different tissues at different times of the incubation period

-   Inherent characteristics of cattle, such as age-related
    susceptibility

> IV.A.2.a.1. *[Current (2006) updates to the BSE Exposure
> Model]{.underline}*
>
> *[and input parameters]{.underline}*

In order to evaluate the effects of importing cattle born on or after
March 1, 1999 from Canada and to incorporate newly available evidence,
the author has modified the model in the following ways:

-   Cohen, et al. (2001; 2003) evaluated a single importation of
    infected cattle introduced at the beginning of the simulation. The
    current revision allows for repeated importations of infected cattle
    and specification of the age at import, sex, animal type (dairy,
    beef slaughter, or reproductive beef), age at infection, and
    expected slaughter age.

-   Explicit modeling of potential cattle exposure to the BSE agent via
    administration of poultry litter in cattle feed. The simulation
    model incorporates the proportion of prohibited MBM used in poultry
    feed (separate values are specified for dead and healthy slaughter
    cattle), and the proportion of poultry litter that is administered
    intentionally as cattle feed (Attachment 2, Section 2.1.8).

The current version of the model also incorporates updated parameter
estimates:

-   Efficacy of SRM removal at slaughter

-   Proportion of animals that are rendered

-   Mislabeling and cross-contamination at rendering

-   Mislabeling and cross-contamination at feed mills

-   Disposition of MBM

-   Pessimistic value of misfeeding for sensitivity analysis

These parameters are described in the following sections along with
parameter updates employed in Cohen and Gray 2005, and other
significant, although unchanged parameters. In order to be consistent
with its historic use in the Harvard model and in Attachment 2, we use
the term "pessimistic values" in this context to refer to the plausible
higher values used in the sensitivity analysis.

> IV.A.2.a.2. *[Significant and/or updated (2005-2006)
> parameters]{.underline}*

The following discussion enumerates and provides the rationale for
changes in the input parameters most relevant to our analysis. These
changes are consistent with new BSE mitigations, compliance data, and
new data on key parameters known to influence the spread of the disease.
They include relevant changes made in a recent update of the model
performed for USDA FSIS (Cohen and Gray 2005), and new changes
implemented specifically to inform the current risk assessment.

In addition to revisions in the model and its parameters, we also
discuss the most important nodes in the risk pathway. Other nodes that
have not been deemed to be epidemiologically important (such as maternal
transmission or the feeding of plate waste or tallow to cattle) are
addressed in earlier publications (Cohen, et al. 2001; 2003) and are not
revisited here.

> IV.A.2.a.2.(a) Import of infected cattle

As described in the release assessment, the numeric representations of
the number of infected cattle introduced into the United States are
based on (1) August 2006 estimates of the BSE prevalence in Canada
(Section III.A. and Attachment 1), and (2) the number of cattle we
expect to import over the 20 years of the analysis (Section III.C.).
Table 7 (Section III.D.) shows the estimates for the number of infected
animals imported by age, sex, and type for the first year in which the
proposed rule may be implemented, 2007.

The most likely assumption, which we have not attempted to quantify, is
that the prevalence will continuously decrease from the current estimate
over the 20-year analysis period. In this assumption, the possible
numbers of infected animals imported is highest in the first year in
which the proposed rule may be implemented, and subsequently decreases.
This assumption does not provide numeric estimates of the importation of
infected animals necessary for simulation in the exposure model.
Therefore, the exposure model and its results by necessity include the
less likely assumption that Canadian BSE prevalence remains constant
through 2026.

Based on these numeric representations of BSE release from Canada, the
attached, updated exposure model evaluates the outcome of the
introduction of infectivity assuming BSE prevalence in Canada is 6.8 x
10^-7^. This estimate incorporates the UK data on the effect of a feed
ban.

Although the release section produces two numeric estimates of BSE
prevalence in Canada, the proposed mitigation requiring that all
imported live bovines are born on or after March 1, 1999 means that
these animals are subject to the feed ban. We therefore focus our
discussion of the impacts of the proposed live animal imports on results
predicted when assuming that Canada's feed ban has reduced BSE
prevalence as effectively as that observed in the UK. We evaluate the
impact of relaxing this assumption in the sensitivity analysis, in which
we analyze the model's outputs assuming the higher prevalence value (3.9
x 10^-6^) which omits the additional UK evidence.

Once infected animals are introduced into the system, the model
evaluates how mitigations during slaughter, rendering, and feed
production reduce the amount of infectivity potentially available to be
recycled and fed to bovines.

> IV.A.2.a.2.(b) Slaughter process

BSE infected animals showing clinical signs of disease are at the end of
the incubation period and therefore carry a high infectivity load
(Wells, et al. 1996; 1998). Therefore, identification of high risk
animals, including those displaying clinical sign of BSE infection at
ante-mortem inspection, reduces the probability that these animals and
the large amount of infectivity they may carry will enter the normal
slaughtering process. As part of the ante-mortem inspection, FSIS
veterinarians routinely condemn animals showing clinical signs of
systemic disease, non-ambulatory status and/or exhibiting clinical signs
compatible with BSE, including central nervous system impairment. For
standard surveillance, a condemnation of an animal exhibiting clinical
signs of BSE triggers a diagnostic investigation of the suspect animal,
including a test for BSE. If positive the animal is destroyed mainly by
incineration.

The scenarios simulated in the attached exposure model (Attachment 2)
reflect current mitigation measures related to the disposition of
non-ambulatory animals and track the ambulatory status of cattle
infected with BSE. Antemortem inspection and ambulatory status
probabilities are based on Cohen and Gray 2005.

In the event that infected animals pass the ante-mortem inspection, many
tissues not used for human consumption, including tonsils and distal
ileum of all animals and nervous tissue-derived SRMs of animal over 30
months old, go to rendering. As in earlier versions of the model, the
author cites FSIS' statement that SRMs are effectively removed 99
percent of the time (FSIS 2005).

> IV.A.2.a.2.(c) Proportion of animals that are rendered

Sick, non-ambulatory and dead animals can either be rendered or disposed
of in other ways (e.g., burial on farm and landfill disposal). Disposal
other than rendering prevents potential infectivity in non-rendered
animals from inadvertently entering cattle feed.

Dead stock that is not disposed of on the farm, animals condemned on
antemortem inspection at slaughter and non-ambulatory cattle from all
types of cattle operations are typically collected by rendering firms.
Eastern Research Group, Inc. (ERG 2005) and Informa Economics (Informa
2004) prepared detailed estimates of farm mortalities and materials
rendered. Informa (2004) estimates that approximately 35 percent of
cattle found dead on farm and downers in the United States are rendered
(41.9 percent rendered by volume). In contrast, ERG (2005) using other
industry-supplied data estimated that the number of cattle mortalities
and downers rendered is 17 percent.

In response to comments on its initial analysis and in recognition of
the uncertainty about this parameter, FDA substituted new industry data
into the analysis, revising its estimate from 17 to 33 percent with an
upper bound of 42 percent (FDA 2005a, page 58588). The current analysis
(Attachment 2) assumes the higher value of 42 percent to reflect those
cattle dying on farm that are rendered. This parameter value is lower,
however, than the 85 percent assumed in previous analyses (Cohen, et al.
2001; 2003).

> IV.A.2.a.2.(d) Rendering process

Although rendering of infected bovines can potentially allow BSE
infectivity to pass into ruminant feed, several mitigations diminish its
likelihood of doing so. FDA's 1997 feed ban (FDA 2006) requires that
renderers must (1) keep specific records on the manufacture of rendering
products, (2) have processes in place to prevent commingling of ruminant
and non-ruminant MBM, and (3) ensure that materials containing
prohibited MBM are labeled conspicuously with the statement, "Do not
feed to cattle and other ruminants." Furthermore, as discussed below,
rendering itself serves as an effective mitigation against the
perpetuation of infectivity.

> IV.A.2.a.2.(d)i. [Inactivation during rendering]{.underline}

Although rendering practices vary among plants, the Harvard model
(Cohen, et al. 2001; 2003; Cohen and Gray 2005) cite evidence from
industry sources, estimating that 95 percent of ruminant MBM is produced
using processes that result in at least one log reduction in BSE
infectivity. Specifically, 5 percent of ruminant MBM is rendered using a
batch system that reduces infectivity by 3.1 logs; 45 percent of MBM is
rendered using a continuous flow system to which fat is added that
reduces infectivity by 2 logs; and 45 percent of MBM is rendered using a
continuous flow system without fat added that reduces infectivity by 1
log. Only 5 percent of MBM is rendered using a vacuum system that
results in no reduction in BSE infectivity. The infectivity reduction by
type of rendering system is based on inactivation studies (Taylor, et
al. 1995; 1997).

We used this evidence to calculate the expected (average) reduction in
infectivity from rendering to be 1.4 logs. Thus, roughly 96 percent
(1-10^-1.4^) of BSE infectivity is destroyed during rendering allowing
only 4 percent of BSE infectivity to survive the rendering process.

> IV.A.2.a.2.(d)ii. [Cross-contamination and mislabeling at
> rendering]{.underline}

The likelihood of cross-contamination and mislabeling at rendering
depends in large part on the potential presence of risk materials in the
facility. Cohen, et al. (2001; 2003) assume that nearly 50 percent of
raw material from ruminants is delivered to rendering plants that
process only prohibited material, eliminating the possibility of
cross-contamination at the renderer (although mislabeling is still
possible). Citing industry sources, the authors also assumed that
approximately 5 percent of such high risk material is delivered to
rendering plants that process both prohibited and non-prohibited
material (so-called mixed rendering plants). In these facilities, both
cross-contamination and mislabeling are possible. We assume that no
mislabeling or cross-contamination occur at dedicated "non-prohibited"
rendering facilities.

In order to estimate mislabeling and contamination probabilities, we
rely on data collected by FDA/CVM[^14] prior to September 2003. Compared
to more recently collected inspection data, these data better detail the
nature of the violations discovered, reporting the total number of firms
with at least one violation and designating each violation as a case in
which: 1) products were not labeled as required, 2) the facility did not
have adequate systems to prevent co-mingling, or 3) the facility did not
adequately follow record keeping regulations. More recent data report
violations only in terms of the type of action indicated -- *i.e.*,
Official Action Indicated (OAI), Voluntary Action Indicated (VAI), or No
Action Indicated (NAI)[^15].

As described in Cohen and Gray 2005, these compliance data indicate that
mislabeling was detected in 2.3 percent of inspected renderers and
possible commingling (cross-contamination) was detected in 1.8 percent
of inspected renderers. The model uses these values to indicate the
relative likelihoods of these nodes within the risk pathway. Both of
these values reflect decreases from higher estimates based on older
compliance data used in earlier versions of the Harvard BSE exposure
model. Additional details on these parameter values are in the attached
exposure model document (Attachment 2). We note here, however, that the
use of these data is likely to produce compliance estimates that are
lower than current levels because compliance rates with the FDA
regulation improved since 2002. For example, the FDA/CVM update of June
2005 (FDA CVM 2005) indicates that 2 (1.1 percent) out of 176 rendering
firms handling prohibited materials were classified as OAI.

> IV.A.2.a.2.(e) Disposition of meat and bone meal

The revised BSE exposure model includes updates on the disposition of
rendered materials. In previous versions, the authors estimated that 15
to 30 percent of MBM produced in the United States was exported. This
percentage dropped substantially in 2004 to 5 percent of production (NRA
2005). In addition, because the current model explicitly addresses the
poultry litter pathway, the proportion of MBM destined for poultry feed
needed to be specified. To incorporate both of these changes to the
model, we assume that 50 percent of prohibited MBM goes to feed mills
producing prohibited feeds (excluding poultry feed); 5 percent of
prohibited MBM goes to mixed feed mills and the remaining 40 percent
goes to poultry feed mills. In addition to the poultry litter pathway,
ruminant MBM from both dedicated prohibited material renderers and mixed
rendering plants that may contain infectivity may be incorporated into
ruminant feed if it is mislabeled at the feed mill as non-prohibited
feed.

The updated BSE exposure model (Cohen and Gray 2005; Attachment 2) also
adjusts for increases in the proportion of exported non-prohibited MBM
to 30 percent (NRA 2005). This proportion and those going to other feed
mill types are presented in Table 8, along with the respective parameter
values used in earlier versions of the model.

**Table 8. Differences in the parameter regarding the disposition of MBM
used for the Cohen, et al. 2001/2003\* and 2005/2006 Risk Assessments**

+------------------------+------+------+------+------+------+------+
|                        | **Pr |      | **No |      | *    |      |
|                        | ohib |      | n-Pr |      | *Mix |      |
|                        | ited |      | ohib |      | ed** |      |
|                        | Re   |      | ited |      |      |      |
|                        | nder |      | Re   |      | **Re |      |
|                        | er** |      | nder |      | nder |      |
|                        |      |      | er** |      | er** |      |
+------------------------+------+------+------+------+------+------+
|                        | *    | **   | *    | **   | *    | **   |
|                        | *P** | NP** | *P** | NP** | *P** | NP** |
+------------------------+------+------+------+------+------+------+
| P Feed Producer (other | 50%  | 50%  | NA^  | 50%  | 50%  | 50%  |
| than poultry feed)     | (    |      | (a)^ |      |      |      |
|                        | 63%) | (    |      | (0%) | (    | (0%) |
|                        |      | 63%) |      |      | 63%) |      |
+------------------------+------+------+------+------+------+------+
| NP Feed Producer       | 0%   | 10%  | NA^  | 10%  | 0%   | 10%  |
|                        |      |      | (a)^ |      |      |      |
|                        | \    | \    |      | (    | (0%) | (    |
|                        | (0\) | (0\) |      | 85%) |      | 85%) |
+------------------------+------+------+------+------+------+------+
| Mixed Feed Producer    | 5%   | 10%  | NA^  | 10%  | 5%   | 10%  |
|                        |      |      | (a)^ |      |      |      |
|                        | (5%) | (5%) |      | (5%) | (5%) | (5%) |
+------------------------+------+------+------+------+------+------+
| Poultry Feed Producer  | 40%  | 0%   | NA^  | 0%   | 40%  | 0%   |
|                        |      |      | (a)^ |      |      |      |
|                        | (    | (    |      | (    | (    | (    |
|                        | NA)^ | NA)^ |      | NA)^ | NA)^ | NA)^ |
|                        | (b)^ | (b)^ |      | (b)^ | (b)^ | (b)^ |
+------------------------+------+------+------+------+------+------+
| Out (Unavailable to    | 15%  | 30%  | NA^  | 30%  | 5%   | 30%  |
| U.S. Cattle)           |      |      | (a)^ |      |      |      |
|                        | (    | (    |      | (    | (    | (    |
|                        | 32%) | 32%) |      | 10%) | 32%) | 10%) |
+------------------------+------+------+------+------+------+------+

> \*Values for the Cohen, et al. 2001/2003 risk assessments are in
> parenthesis
>
> Abbreviations: P -- prohibited, NP -- non-prohibited, NA -- not
> applicable

(a) We assume no product from a non-prohibited renderer is labeled as
    prohibited

(b) Poultry feed producer was not modeled in the 2001/2003 Risk
    Assessments

> IV.A.2.a.2.(f) Feed manufacturing process

The FDA's ruminant feed regulations (21 CFR 589.2000) (FDA 2006)
prohibit the inclusion of high risk source materials in ruminant food.
However, some prohibited MBM might cross-contaminate non-prohibited
feed, or prohibited feed may be mislabeled as non-prohibited.
Information on mislabeling and contamination during the feed
manufacturing process used in Attachment 2 is based on 2002 FDA feed ban
compliance data (FDA 2002). These data report that 4 percent of
prohibited feed is mislabeled, and 1.9 percent of prohibited feed
cross-contaminates non-prohibited feed. These values replace higher,
less certain estimates used in earlier versions of the model. Table 2 in
Attachment 2 shows the differences in the parameter values associated
with the handling of prohibited materials during the feed manufacturing
process used for the Cohen, et al. 2001/2003 and the 2006 risk
assessments.

Although lower than previous estimates, the values used are still higher
than suggested by more recent compliance data. Such data show that from
a total of 9,575 inspections of feed mills conducted during the fiscal
year 2004 and the first half of the fiscal year 2005, 165 firms (1.7
percent) were identified as firms handling animal feeds containing
prohibited mammalian protein that were not meeting the labeling
requirements. In addition, of the 9,575 inspections of feed mills, 41
(0.4 percent) of the inspections identified cross contamination or
commingling problems in firms that handle animal feeds containing
prohibited mammalian proteins (FDA 2005a). Therefore, as for the
rendering data above, we conclude that our higher 2002 estimates
over-estimate the amount of cross-contamination and mislabeling that
currently occurs in feed mills.

> IV.A.2.a.2.(g) On-farm misfeeding

We recognize that even if all of the above safeguards are 100 percent
effective in preventing contamination of ruminant feed with potentially
infective prohibited material, cattle may be exposed to such materials
via misfeeding on the farm. This pathway is in parallel to and therefore
additive with those prohibiting cross-contamination and mislabeling of
rendered material and feed. However, like cross-contamination and
mislabeling, the potential impact of, and mitigations from the
prohibition on misfeeding are in series, and hence multiplicative with
all of the risk reduction steps occurring up through rendering.

The base case scenario for Cohen, et al. (2001; 2003) assumes that 1.6
percent of correctly labeled prohibited feed is misfed to cattle, with a
pessimistic estimate of 30 percent used in the sensitivity analyses.
Since the sensitivity analyses have shown that this parameter is very
influential, (Cohen, et al. 2001; 2003), the National Grain and Feed
Association and the American Feed Industry Association provided new data
for the estimates (NGFA and AFIA 2005). Their data indicate that while
the original expected value of 1.6 percent is reasonable, the
pessimistic value used in the sensitivity analyses should be reduced to
5 percent.

> IV.A.2.a.2.(h) Poultry litter exposure pathway 

As described in the section on disposition of MBM, current FDA
regulations allow the use of ruminant MBM (prohibited MBM) in poultry
feed. In the United States, poultry litter can be legally used as a
feedstuff for ruminants. Because poultry feed may contain ruminant meat
and bone meal which is prohibited in ruminant feed, there is a potential
risk that poultry litter may contain spilled poultry feed or potentially
intact infectivity excreted in fecal waste. Cattle fed the poultry
litter may then be exposed to infected materials. The current assessment
incorporates this potential pathway into the larger evaluation of the
risk of the importation of infected Canadian cattle. Like misfeeding,
the poultry litter pathway is additive to the controls implemented to
prevent cross-contamination and mislabeling, and is multiplicative to
the controls up to and including rendering.

Poultry litter is a waste by-product of poultry production, containing
bedding material, fecal matter, feathers and spilled poultry feed. It is
generally only used as cattle feed in particular geographic areas in
major broiler producing states where cattle and poultry production
enterprises are in close proximity. Since the exposure model simulates
the fate of infectivity in the entire U.S. herd, we use information
provided by relevant industry representation (Custer personal
communication 2005), estimating that on average, 1 percent of poultry
litter nationwide will be used in cattle feed.

We assume that prohibited ruminant protein (and any infectivity which it
may contain) is most likely to enter poultry litter via spilled poultry
feed. We are uncertain, however, of the proportion of infectivity that
enters the litter. We therefore over-estimate this proportion by
assuming that 100 percent of any infectivity that may be in poultry feed
goes to the litter.

> IV.A.2.a.3. *[Sensitivity analysis]{.underline}*

The exposure model includes a sensitivity analysis to identify
potentially important assumptions. These assumptions were evaluated by
holding all but one set of assumptions equal to their base case values.
The set of assumptions were set to pessimistic values to see if doing so
influences key model predictions -- in particular, for this analysis,
the predicted number of cattle infected with BSE in the United States
over a 20 year period. In addition to determining if the parameters
impact the outputs, the sensitivity analysis also provides a ranking of
the parameters with respect to the relative magnitude of their effects.

The parameters analyzed include four "endogenous" factors inherent to
the U.S. system that influence the fate of introduced infectivity, and
one "exogenous" factor, external to the system, that influences the
amount of infectivity introduced. The endogenous parameters assessed in
the sensitivity analysis are:

\(1\) Mislabeling and contamination -- We have revised the base case
values for these parameters to take into account new data on compliance
rates. The sensitivity analysis evaluates the impact of these revisions
by using the previous base case values from Cohen, et al.'s 2003 report
as the pessimistic values in the current analysis. In particular, for
the sensitivity analysis we increase the mislabeling rates to 5 percent
for both MBM and feed production. We increase contamination rates to 14
percent for MBM production, and 16 percent for feed production
(Attachment 2 Section 2.2.4).

\(2\) Misfeeding -- The base case value for this parameter is 1.6
percent. We investigate the impact of using the pessimistic value of 5
percent for this parameter (Attachment 2 Section 2.2.9).

\(3\) The render reduction factor -- We change the distribution of
render reduction factors using the worst case assumptions for this
parameter from Cohen et al.'s October 2003 report.

\(4\) The proportion of poultry litter used in cattle feed - The base
case value for this parameter is 1 percent. The sensitivity analysis
investigates use of 5 percent for this parameter.

The exogenous parameter assessed in the sensitivity analysis is:

\(5\) Importation of infected animals as a function of Canadian
prevalence estimate -- Using the BSurvE method described in Section
III.A. we can assess the impact of imports from Canada assuming a higher
Canadian BSE prevalence estimate. In particular, omitting the additional
information on the impact of the UK feed ban from the calculation
provides a BSE prevalence estimate for Canada of approximately 3.9 x
10^-6^, nearly six times higher than the base case prevalence (6.8 x
10^-7^) which includes the assumption of the impact of a feed ban.

In the final sensitivity analysis scenario, all six uncertain parameters
were simultaneously set to their pessimistic levels. Doing so allows us
to explore the impact of this unlikely, but possible situation.

IV.A.2.b. *Results*

> IV.A.2.b.1. *[Base Case Results]{.underline}*

The following paragraphs summarize the results from the model
simulations. As previously noted, the most likely prevalence assumption
-- the prevalence decreases continuously -- was not included in these
simulations. Therefore, the base case as described reflects the less
likely assumption that the prevalence stays the same for the period of
this analysis.

Under base case conditions, our results indicate that the expected
number of infected cattle occurring in the United States over 20 years
as a result of importing cattle from Canada is 21 animals. Most of these
infected animals (90 percent) would be imported directly, while the
remaining 10 percent (approximately 2 animals) would represent secondary
infections (i.e., native U.S. cases). Of the 21 in the United States,
0.67 animals would survive to show clinical signs (Attachment 2,
Appendix 2A). The expected (average) value of the reproductive constant
for BSE (R~0~) is far less than 1 (0.04), indicating no possibility of
establishment of BSE in the United States as a result of the
introduction of potential infectivity from Canada.

We are 95 percent confident that at base case levels, the total number
of infected animals in the United States over 20 years of the analysis
will not exceed 30 animals. We are also 95 percent confident that there
will be 24 or fewer animals imported and six or fewer native U.S. cases
(Attachment 2, Appendix 2A). In addition, we are 95 percent confident
that under base case assumptions, R~0~ will not exceed 0.25.

> IV.A.2.b.2. *[Sensitivity Analysis Results]{.underline}*

The sensitivity analysis indicates that, of the endogenous parameters,
the most important sources of uncertainty are the misfeeding rate and
the extent to which poultry litter is used in cattle feed (Attachment
2).

The exogenous source of uncertainty, the prevalence estimate with its
resulting release of infected animals, is the most important source of
uncertainty. The higher value used in the sensitivity analysis is 5.7
times greater than that used in the base case. Not surprisingly, the
number of imported infected animals (108) and the number of new cases
(12) are 5.7 times greater than those expected in the base case. The
R~0~ value of 0.075 is only slightly higher than that at the base case
(0.04), reflecting that the U.S. system is essentially unchanged by
additional introduced infectivity.

When using pessimistic values for all five uncertain parameters
analyzed, the average number of total infected cattle (including
imports) over the 20 years of the analysis is 150. Of these, 42 are U.S.
born animals and less than 8 survive long enough to develop clinical
signs. Furthermore, in this highly unlikely scenario, the reproductive
constant, R~0~, remains consistently less than 1, with an expected value
of 0.23 (Attachment 2, Appendix 2A). That is, even under the worst set
of assumptions considered here, BSE infectivity introduced via live
animals from Canada will not establish, and will instead disappear from
the population.

> IV.A.3. Live Animal Qualitative Exposure Assessment

As discussed in the release section (Section III.D.), evidence indicates
that implementation of a ruminant feed ban results in decreasing BSE
prevalence over time. Therefore, in the most likely scenario, prevalence
will decrease in Canada over the next 20 years. In addition, the
proposed mitigation (imported animals must be born on or after March 1,
1999) would ensure that imported animals are less likely to have been
exposed to the BSE agent. Finally, based on ERS projections, the
majority of imports are expected to be less than two years of age at the
time of import. For example, approximately 75 percent of animals
imported in 2007 would have been born in 2005 or later (Table 4). As the
20-year time frame for the analysis proceeds, these animals would be
born an increasingly longer time after the feed ban was effectively
enforced. However, without a quantitative estimate for the precise rate
at which Canada's BSE prevalence may fall, we cannot produce numeric
values that accurately represent this scenario.

In addition, the import projections indicate that a higher number of
imports would be expected in 2007, the first year that the proposed rule
could be implemented. When this projection is combined with the BBC
prevalence estimate -- determined to be more applicable to the current
proposal -- less than one infected animal would be expected to be
imported that year. With the expectation that the prevalence would
decrease, and the mitigative effects of both the import requirements and
the young age of animals at the time of import, the highest likelihood
of release would be in 2007. Qualitatively, we would therefore expect
that prevalence, release, and hence, the number of infected animals
occurring in the United States as a result of exposure, would be lower
than any of the results of the quantitative model.

> IV.A.4. Live Animal Exposure Summary

In summary, if infectivity at the levels analyzed, either quantitatively
or qualitatively, were introduced into the United States from Canada,
biological factors (e.g., age-dependent susceptibility), and mitigations
reducing the likelihood of transmission at slaughter, rendering and feed
manufacturing and use, prevent BSE amplification in the United States.
Furthermore, the quantitative model produces estimates of the
reproductive constant, R~0~, that predict that any imported infectivity
will ultimately disappear from the population.

IV.B. *Qualitative exposure assessment for blood and blood products
imported from*

*Canada*

In the release assessment, we presented evidence that bovine blood and
blood products from Canada are highly unlikely to carry BSE infectivity
into the United States. According to the OIE's risk assessment
guidelines (OIE 2006b), if the likelihood of release is determined to be
negligible, the assessment may be concluded. However, in order to
maintain consistency in our approach across the three commodities
considered, we have elected to assess the exposure and consequences
associated with all the commodities, even if their likelihood of release
is negligible. Therefore, in this section, we assess the likelihood of
exposure to infectivity if, despite the evidence, such commodities were
indeed contaminated with the BSE agent. Because the primary blood
products imported into the United States for use in manufacture of
veterinary biologics and drugs are fetal bovine serum (FBS) and bovine
serum albumin (BSA), we focus our analysis on the potential exposure
pathways associated with those products.

The pathways under consideration are those which might allow potential
BSE infectivity in imported FBS and BSA to persist through the steps in
the manufacture of animal biologics and pharmaceuticals, and result in
cattle exposure to, and subsequent infection with BSE. As explained in
Section III.B.2, we utilize TSE studies on other species because no
comparable work can be done on BSE in cattle blood, given that it has
never been detected.

IV.B.1. [Risk mitigation by processing of FBS and other blood
products]{.underline}

Extrapolating from studies in other species, we expect that some of the
processing steps used in preparation of FBS and BSA and the products
derived from them further reduce the likelihood of BSE transmission.
Those steps which may result in mitigation of BSE risk by removal
through separation techniques, potential inactivation through gamma
irradiation, and dilution, are discussed here.

Several reasons have been given for the marked decrease in TSE
infectivity during these separation processes. The pathogenic
conformation of the prion protein (PrPSc) has a low solubility in
aqueous solution, forms aggregates readily, and has an affinity for
adhering to surfaces (Foster 1999). These attributes contribute to the
reduction of the likelihood of BSE transmission via FBS and BSA through
centrifugation and filtration (Foster 2004), processes which are used in
the preparation of FBS and plasma fractions and in the collection of
cell culture products for use as biologics or in the manufacture of
pharmaceuticals.

Plasma, serum and other derivatives are obtained from various processes
applied to whole blood. Serum is derived from whole blood through the
following process. Whole blood is collected into sterile blood bags and
is allowed to clot. The clotted blood is centrifuged for removal of the
clot and separation of serum from the blood cells. This initial
separation step has been demonstrated to remove TSE infectivity from
other species' serum fraction (Brown, et al. 1999; Houston, et al. 2000;
Hunter, et al. 2002; Brown, et al. 1998). The resulting serum may
include nutrient proteins, growth factors, hormones, lipids, minerals,
and metabolites necessary for cell culture. The serum is decanted,
prefiltered, pooled with a variable number of other animals' serum,
sterile filtered, and frozen. Because of the properties described in the
preceding paragraph, the decanting and filtration steps would further
remove any infectivity that might possibly have remained in the serum.
Furthermore, the pooling step would dilute any single donation from a
subclinical case of BSE.

Pooled FBS is subjected to filtration using 0.1-0.2 micron filters and,
for cell culture applications, irradiated to mitigate the likelihood of
potential contamination by bacterial and viral agents. According to
APHIS Center for Veterinary Biologics records, gamma irradiation is
applied commercially at c. 25-50 kiloGray (2.5-5 megaRad) prior to its
use in vaccine production. Most commercially applied mitigations are
appropriate for prevention of bacterial and viral disease transmission
via blood-derived biologics. TSE infectivity, however, is in general
highly resistant to conventional inactivation techniques (Taylor 2003).

Unlike heating and other standard steps to ensure freedom from microbial
contaminants, gamma irradiation may reduce BSE infectivity. Miekka, et
al. 2003 demonstrated that scrapie was inactivated by an estimated 1.5
log~10~ in human albumin 25 percent solution, using 50 kGy, while
causing only moderate alterations to the albumin. We do not, however,
have direct evidence for the efficacy of gamma irradiation as a BSE
mitigation in bovine blood products. Thus, although we may speculate
that slightly lower levels of gamma irradiation used to prevent the
transmission of viruses in commercially processed bovine sera may have
some mitigative effects on levels of BSE infectivity, we have no direct
evidence of such.

To prepare plasma products from whole blood, anticoagulants such as
sodium citrate or EDTA are added to the collection receptacle to prevent
clotting. This blood, collected generally from live adult bovines, is
then centrifuged and filtered. Using fractionation techniques such as
cryoprecipitation, centrifugation and filtration, plasma is commercially
separated into various components, among which are Fraction II
containing immunoglobulins and Fraction V containing albumin (BSA)
(Comer 2004, p. II.23). In experimental rodent models, several studies
have shown that the very low level of plasma infectivity is dramatically
reduced during this fractionation process (Brown 2001). It has been
observed that discarding of Fraction III and Fraction IV from
immunoglobulin and from albumin, respectively, results in further TSE
removal for various strains (scrapie, BSE, CJD) in rodent models (Foster
2004). Separation is achieved by removal of the precipitate. The
supernatant and sometimes a redissolved precipitate are then commonly
clarified by further filtration. Because of the BSE agent's properties
described above, these additional separation steps would further reduce
the likelihood of BSE transmission. The overall process reduction
factors for TSE infectivity of the various plasma proteins have been
estimated to be quite large. For example, the infectivity reduction
factor is 10^13^ for albumin and 10^9^ for immunoglobulins (Foster
1999).

Although whole blood or buffy coat transfusion has resulted in
experimental transmission of BSE or scrapie between sheep (Hunter, et
al. 2002), and in iatrogenic transmission of vCJD between persons in the
UK (Farshid, et al. 2005), transmission by other blood products has not
been demonstrated in natural animal hosts of TSEs nor in natural
infection of animals or humans (Brown 2001). No transmissions of vCJD
have been attributed to plasma derivatives, even among such groups as
hemophiliacs that must often use these products (Taylor 2003; WHO 2003).
We infer that these observations may result from the reduction in TSE
infectivity due to the fractionation processes used in the preparation
of these products.

> IV.B.2. [FBS and blood product use in veterinary vaccine and
> drug]{.underline}
>
> [manufacture]{.underline}

FBS is used as a nutrient in cell culture growth media during production
of viral vaccines and to propagate difficult-to-grow microorganisms. The
basic steps for production of veterinary vaccines are equivalent to
those used in the production of human vaccines (FDA 2001). Both often
require FBS and sometimes BSA, used as growth media or as stabilizers in
a number of biological products, supporting bacterial growth and cell
cultures that propagate virus.

The cell lines used in vaccine production are not permissive for prion
replication (Harris 1999; Solassol, et al. 2003), so there is no
opportunity for amplification of possible TSE contamination. The vaccine
virus is grown and harvested from the cell culture, and largely
separated from the cell supernatant containing the FBS. There may be
trace amounts of FBS remaining in the viral pellet, but this represents
a minute amount of the final vaccine dose. Thus, even if BSE-infected
FBS were used in bovine vaccine production, the FBS itself does not
remain in the final product in amounts adequate to result in infection.

The evidence presented here demonstrates the sequential barriers to
exposure to BSE infectivity from blood and blood products imported from
Canada:

1.  prion protein has a low aqueous solubility, readily forms aggregates
    and adheres to surfaces, reducing the likelihood of it persisting
    through the various separation and filtration steps throughout the
    FBS and vaccine manufacture process;

2.  blood products such as BSA pass fractionation steps that further
    reduce the likelihood of BSE being transmitted;

3.  the additional steps in the manufacture of vaccines and other
    products serve to separate potential infectivity from the processed
    product.

This evidence is further supported by the absence of an epidemiologic
link between vaccine administration and clinical cases of BSE in cattle
(WHO 2003). Therefore, we conclude that even if BSE were present in
bovine blood products collected in Canada, the likelihood of exposure of
animals in the United States to such infectivity is negligible.

IV.C. *Qualitative analysis for exposure resulting from the importation
of small intestine*

*other than the distal ileum*

In the preceding release assessment, we demonstrate that the likelihood
for the introduction of BSE infectivity in imported of bovine intestine
from Canada is extremely low. In this section, we evaluate the pathways
by which BSE infectivity could potentially expose U.S. cattle, if
despite our earlier findings it were released in imported bovine small
intestine other than the distal ileum. We also assess the likelihood
that these pathways might lead to exposure that could potentially cause
animal disease and the establishment of BSE in the U.S. cattle
population.

As described in Section IV.A., the feeding to ruminants of ruminant
protein is expressly prohibited by FDA (21 CFR 589.2000, FDA 2006). This
feed ban applies to both non-edible intestine, as well as that intended
for human consumption. Therefore, exposure of cattle to BSE infectivity
assumes subsequent misdirection, mislabeling, misfeeding, or
cross-contamination in feed processing. As demonstrated in the
quantitative exposure assessment for imported live bovines, spread via
these various pathways is extremely rare, even when considering
importation of entire animals. We infer, therefore, that imported
Canadian bovine intestine is highly unlikely to be fed to U.S. cattle,
or lead to spread of BSE.

We recognize that some small fraction of imported inspected and prepared
for human consumption may be legally offered per FDA's "plate waste"
exemption[^16]. However, very few firms are processing human waste food
for ruminant consumption (Pritchett 2004 personal communication).
Furthermore, since FDA requires that the plate waste be further heat
processed for feed, it may be subject to rendering processes that can
inactivate the agent, further reducing the level of infectivity in MBM
(Cohen, et al. 2001; 2003).

Given the above evidence, we conclude that exposure of U.S. cattle to
BSE in bovine small intestine imported from Canada is extremely
unlikely. Therefore, the likelihood of infection and subsequent
establishment of the disease in the U.S. cattle population is
negligible.

V.  **Consequence Assessment**

In accordance with OIE's guidelines, the first two sections of this
animal import risk assessment examine the *likelihood* of BSE release
and exposure. The consequence assessment is intended to address the
*impacts* expected if, despite the likelihood of release and exposure
estimated in the preceding sections, new cases of BSE were to occur in
the United States. Consequences requiring consideration are economic and
environmental. To fulfill obligations under the National Environmental
Policy Act (NEPA), impacts to the human environment are addressed in the
accompanying environmental assessment. The following discussion
addresses the economic impacts that we would expect if additional BSE
cases were to result from the proposed regulatory change. Following
OIE's guidelines, we subsequently combine the impacts described in the
consequence assessment with the likelihoods described in the release and
exposure assessments to evaluate the overall risk in the risk estimation
section.

The economic impact of BSE includes a variety of costs; some are
long-term costs that continue regardless of new cases, others are
one-time costs associated with new cases. One long-term impact is the
potential loss from actions taken by foreign governments to restrict
imports of U.S. live bovines, beef and beef products. These tend to
decline over time as exporting and importing countries find ways to
resume mutually beneficial trade while maintaining the safety of the
beef supply. International organizations such as OIE have developed
international science-based standards to permit safe international trade
in beef from countries that have BSE. U.S. producers incur other
long-term costs by complying with domestic regulations to protect animal
and human health. U.S. producers and processors must comply with a
variety of regulations designed to prevent the BSE agent from entering
the ruminant feed chain and to prevent potentially infected ruminant
tissues from entering the human food chain. U.S. regulations pertaining
to SRM removal, restrictions on use of SRMs, and other changes mandated
of the beef processing and feed processing sectors are examples of this
type of impact. Another long-term cost is that for BSE surveillance
which will continue into the foreseeable future.

The impacts of any new cases of BSE are confined to the incremental
costs associated with those actual cases. These potential impacts are of
two types, regulatory costs and domestic market impacts from consumer
reaction to additional BSE cases. Based on the U.S. experience with
native BSE cases detected, the regulatory costs per case total
approximately \$250,000 for epidemiological investigations and indemnity
costs for animals sacrificed as part of those investigations.

The potential domestic market impacts from any new BSE cases are
difficult to predict, in part because they may depend on how many new
cases are found in a particular time period (Coffey, et al. 2005). The
results of a mail survey of approximately 2,500 persons in 2004 showed
significant differences in consumers' responses depending on how many
hypothetical new BSE cases were reported (Coffey, et al. 2005). Other
surveys performed in 2004 (Coffey, et al. 2005) all reported that
between 15-20 percent of consumers indicated they would reduce beef
consumption if a BSE case were found.

This expressed or stated preference about consuming beef after BSE cases
must be interpreted in light of the U.S. consumers' actual or revealed
preference as shown by their actions. After the first BSE case was found
in the United States in 2003, the annual increase in demand for beef in
2004 was the highest since 1980 (Kansas State University, AgManager Info
2006). According to the same source, demand in 2005 dropped slightly
from 2004 levels, but still exceeded every other year since 1991. Thus,
what American consumers have done in response to a BSE case occurring is
quite different from what was predicted by survey results. Repeated
consumer polls have revealed only a small minority of the population is
concerned about the possibility of being exposed to BSE from U.S. beef
and over 90 percent of the population believes the U.S. beef supply is
safe from BSE (NCBA 2005). Based on this evidence, we find little reason
to expect that additional cases of BSE would have any significant impact
on U.S. beef consumption.

The impact of additional BSE cases on U.S. export markets will probably
also be minimal. After the first U.S. BSE case was discovered, many of
the 114 nations which imported U.S. beef banned our beef and live
animals, but over half -- including our largest export market, Japan -
have resumed importing U.S. beef (USDA 2006)[^17]. The joint U.S.-Japan
press statement for resuming trade in beef and beef products after
market closures in response to finding BSE in the United States
contained a provision noting "additional BSE cases will not results in
market closures and disruption of beef trade patterns without scientific
foundations" (USDA 2004).

Thus, we recognize that ongoing costs of BSE prevention will continue
even in the absence of future cases. The costs that we may expect to be
associated with the investigation of potential future cases are
relatively minor. Finally, we do not foresee significant costs due to
drops in domestic beef consumption or imposition of additional trade
barriers to international export markets.

VI. **Risk Estimation**

The BSE risk associated with the proposed additional imports of bovine
commodities from Minimal Risk Regions (currently, Canada) is the
conceptual product of the likelihood of release, the likelihood of
exposure and the resulting economic consequences. Potential impacts to
the human environment are addressed in the accompanying environmental
assessment.

As in the exposure and release assessments, we estimate the risks
associated with each of the proposed commodity groups separately. We
then combine these respective risks to estimate the cumulative BSE risk
of importing the proposed commodities.

VI.A. *Live bovines*

Release is unlikely because prevalence is low and mitigation requiring
imported animals to be born on or after March 1, 1999 would
significantly decrease the likelihood that those animals had been
exposed to infectivity. We expect the prevalence to decrease
continuously over the next several years. With this effect, any
possibility of release, already low, decreases each year with the
decreasing prevalence (until the disease is eradicated). Although this
scenario is the most likely, the Bayesian Birth Cohort (BBC) approach as
described is surveillance-based and cannot incorporate empirical and
simulated evidence to project expected decreases in prevalence levels
over time. Therefore, our expectation that prevalence in Canada, and
hence release of BSE infectivity will decrease over time, cannot be
incorporated into the quantitative model which informs our exposure
assessment. Based on the evidence presented in this document, APHIS
concludes that the likelihood of BSE release from imported Canadian
cattle born on or after March 1, 1999 is extremely low.

Import of bison is allowed in the proposed rule, but would constitute
such a small fraction of imports (approximately 0.2 percent), that they
are not analyzed separately. We assume that our conclusion of an
extremely low likelihood of release for cattle also applies to bison.

Even though APHIS concludes that decreasing Canadian prevalence is most
likely, we quantitatively analyze the impact of the constant BSE
prevalence produced by the BBC model to simulate potential BSE exposure
in U.S. cattle. This calculation provides a reasonable upper bound on
our estimate of prevalence and subsequent release of infectivity, which
we refer to as "cautious." Using this cautious value, the model
estimates release of approximately 19 infected bovines over the 20 years
of the analysis. As an expression of our uncertainty regarding the
application to Canada's prevalence calculation of the additional UK data
on the efficacy of a feed ban, we performed a sensitivity analysis which
excluded this additional information. That even more cautious, and less
likely, scenario results in the importation 108 infected bovines over 20
years.

Qualitatively, the exposure assessment demonstrated that, because we
expect Canada's prevalence to decrease over time, and because of the
barriers to BSE transmission in the United States, that the likelihood
of BSE exposure and establishment in the U.S. cattle population is
negligible. Quantitatively, the exposure assessment evaluated the impact
of the numbers of infected animals imported using our assumption of
constant prevalence, on the likelihood of U.S. cattle exposure to BSE.
We based our evaluation on the Harvard Center for Risk Analysis BSE
simulation by Cohen et al. (2001, 2003), updated to incorporate new
evidence and domestic regulations and the proposed changes considered
here. This model indicates that even with assumptions that over-estimate
the possible level of infectivity released into the United States, there
is little spread of disease to U.S. animals. The release of
approximately 19 imported infected animals, leads to approximately two
U.S. cases as secondary spread and 0.67 animals showing clinical signs
over the 20 years of the analysis.

The reproductive constant for BSE (R~0~) is far less than the value of
1.0 necessary to maintain disease in the U.S. cattle population. Even
when higher plausible values were applied for all uncertain parameters
evaluated in the sensitivity analysis, R~0~ is 0.23, well below 1.0
(Attachment 2, Appendix 2A).

The significance of this R~0~ value is magnified by the expectation,
despite the assumptions in our models, that BSE infectivity in Canada
(and thus released into the United States) is likely to decrease over
time. Thus, although the results of the BSurvE model assume no change in
prevalence over time, empirical evidence (DEFRA 2006, EC 2005a) and
simulation studies (Cohen, et al. 2001; 2003) suggest that Canada's feed
ban will continue to decrease BSE prevalence in that country. Thus, we
expect the number of native cases to be less than those predicted in our
analysis.

Considering evidence provided in the consequence assessment (Section
V.), we expect that the 0.67 clinical cases that we estimate may occur
over 20 years (equivalent to 1 in 30 years) will result in negligible
economic costs of BSE. Although clinical cases are the only
manifestation of BSE in an animal population, APHIS acknowledges that
the possibility of preclinically infected animals is a concern. Thus,
although human health is not the focus of this assessment, we note that,
even our quantitative model, which includes multiple sources of risk
over-estimation, indicates that over the 20 years of the analysis, only
45 cattle oral infectious dose-50 (ID~50~) units will potentially be
available for human exposure. Although this result is discussed in more
detail in the accompanying environmental assessment (APHIS 2006), we
note here that compared to estimated potential exposure levels in the UK
of 54 million cattle oral ID~50~ units over 24 years (Comer and Huntly
2003), this number is insignificant.

VI.B. *Blood and blood products*

In the release assessment we concluded from presented evidence that
multiple steps in the risk pathway act as safeguards to prevent release
of BSE infectivity from Canada via imported blood and blood products.
First, the BSE prevalence in Canada is extremely low. Therefore, the
likelihood of collecting blood from an infected animal is small. Even if
an infected animal were a source of imported blood or blood products,
several steps, or nodes in the risk pathway act to further diminish the
likelihood of release. The first is that, even in infected bovines, BSE
infectivity has not been detected in blood. Second, the likelihood of
cross-contamination at collection is significantly reduced by the
proposed mitigations. We conclude that the likelihood of release of BSE
infectivity in bovine blood and blood products is negligible.

In the exposure assessment, we further examine the role of various
separation and processing steps in reducing infectivity. We also note
the absence of an epidemiological link between administration of
vaccines manufactured using tissue culture supported by fetal bovine
serum and clinical cases of BSE (WHO 2003). We conclude that the steps
in the production and use of products manufactured with bovine blood or
its derivatives are likely to further reduce any possible infectivity.

Given both the negligible release of BSE and exposure of bovines to any
such introduced infectivity via the importation of bovine blood and
blood products from Canada, we conclude that extremely few or no U.S.
cases of BSE would result. Therefore, the consequences and resulting
risk of their importation are negligible.

VI.C. *Bovine small intestine other than the distal ileum*

In the release assessment we present evidence that the small intestine
of BSE infected cattle has detectable infectivity only in the distal
ileum. Other portions of the small intestine that have been examined do
not contain detectable infectivity. We also supply evidence that FSIS'
and FDA's regulations ensure adequate removal of the distal ileum, thus
effectively mitigating the likelihood of contamination of exported
bovine intestines with infectivity from the distal ileum.

In the exposure assessment, we examine possible pathways for bovine
exposure to infectivity that may potentially be released from Canada in
bovine small intestines other than the distal ileum. We found no
epidemiologically significant exposure pathways. Combining these
findings, we conclude that the joint likelihood of BSE release and
subsequent exposure of bovines to infectivity from imported bovine
intestines other than the distal ileum is negligible. We further
conclude that this negligible likelihood would result in extremely few
or no U.S. cases of BSE. Therefore, the consequences and resulting risk
of the importation of these commodities are negligible.

VI.D. *Conclusion of Risk Estimation for all commodity groups
considered*

We conclude that over the 20 years of the analysis, BSE will not become
established in the United States and that very few, if any, U.S. born
animals will be infected. Release of infectivity into the US via any of
the commodities described is unlikely, as outlined in the qualitative
discussions. However, even if release of some infectivity occurred via
imported live animals -- as in the less likely scenarios modeled
quantitatively -- there is minimal if any spread to native US animals
and the disease does not become established. Economic costs secondary to
BSE introduction via the importation of these commodities will therefore
be negligible.

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[^1]: Under NEPA regulations, "human environment" is interpreted to
    include the natural and physical environment and the relationship of
    people with that environment.

[^2]: The data made available by DEFRA on its website are for Great
    Britain, which does not include Northern Ireland. These data also
    exclude the Channel Islands and Isle of Man. Records published
    elsewhere indicate that the vast majority of BSE cases in the UK
    have been detected in Great Britain (OIE 2006). therefore,
    epidemiologic patterns noted in Great Britain represent the overall
    UK experience.

[^3]: DRG are clusters of nerve cells attached to the spinal cord that
    are contained within the bones of the vertebral column. "DRG" as
    used in this document has the same meaning as the term "dorsal
    spinal nerve root ganglia." Trigeminal ganglia are clusters of nerve
    cells connected to the brain that lie close to the exterior of the
    skull.

[^4]: BSE infectivity is expressed in terms of cattle oral infectious
    dose-50 units (ID~50~). A cattle ID~50~ is defined as the amount of
    infectivity required to cause infection in 50 percent of an exposed
    cattle population (Cohen et al. 2001).

[^5]: Under OIE Terrestrial Animal Health Code 2006 Appendix 3.8.4, BSE
    surveillance points remain valid for 7 years.

[^6]: Plate waste means any edible material originating from kitchens,
    restaurants, catering facilities or the household of the farmer or
    person tending the animals.

[^7]: HAACP is the frequently used acronym for Hazard Analysis Critical
    Control Point, an approach to controlling hazards, such as food
    contaminants, in the manufacturing process.

[^8]: The accompanying environmental assessment (APHIS 2006) must
    consider potential impacts of a proposed action on the human
    environment, including public health.

[^9]: We note that detecting the presence of PrP^Sc^ is not the same as
    demonstrating infectivity. There are many variables that contribute
    to infectivity, and while detecting PrP^Sc^ may indicate that
    infectivity could be present, it does not, by itself, indicate that
    it is indeed present.

[^10]: Steers are bovine males castrated prior to sexual maturity.

[^11]: Heifers are bovine females that have not yet given birth.

[^12]: Stags are male bovines castrated at or near maturity.

[^13]: Calves are young male or female bovine animals under one year of
    age.

[^14]: Compliance program implementation details can be found at
    <http://www.fda.gov/cvm/CVM_Updates/BSE0806.htm>.

[^15]: From the FDA CVM Web site
    (<http://www.fda.gov/cvm/CVM_Updates/BSE0806.htm>): According to
    FDA, "An OAI inspection classification occurs when significant
    objectionable conditions or practices were found and regulatory
    sanctions are warranted in order to address the establishment\'s
    lack of compliance with the regulation. An example of an OAI
    inspection classification would be findings of manufacturing
    procedures insufficient to ensure that ruminant feed is not
    contaminated with prohibited material. Inspections classified with
    OAI violations will be promptly re-inspected following the
    regulatory sanctions to determine whether adequate corrective
    actions have been implemented."

    "A VAI inspection classification occurs when objectionable
    conditions or practices were found that do not meet the threshold of
    regulatory significance, but do warrant advisory actions to inform
    the establishment of findings that should be voluntarily corrected.
    Inspections classified with VAI violations are more technical
    violations of the Ruminant Feed Ban. These include provisions such
    as minor recordkeeping.

[^16]: 21 CFR 589.2000 exempts the feeding of "inspected meat products
    which have been cooked and offered for human food and further heat
    processed for feed (such as plate waste...)."

[^17]: The temporary closure of the U.S. export market to Japan on 20
    January 2006 was a response to a specific commodity concern and not
    to the likelihood of BSE infection in the U.S. herd.