• If you are having problems logging in please use the Contact Us in the lower right hand corner of the forum page for assistance.

Ranchers.net

Scientific Opinion on BSE Risk in Bovine Intestines Question number: EFSA-Q-2009-00226

Adopted: 10 September 2009 Summary (0.1Mb)

Opinion (0.1Mb)

Summary

Following a request from the European Commission (EC), the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on the BSE related risk of bovine intestines used for casings. Regulation (EC) No 999/2001 of the European Parliament and of the Council stipulates that certain tissues from bovine, ovine and caprine animals must be considered as Specified Risk Material (SRM) and must be removed from the food and feed chain to protect the health of consumers against the risk of bovine transmissible spongiform encephalopathies (BSE). The intestines, from the duodenum to the rectum, of bovine animals of all ages are currently included in the list of SRM. The "TSE roadmap" prepared by the EC details the short, middle and long term actions on TSE measures such as SRM removal and sets the objectives to ensure and maintain the existing high level of consumer protection. It allows for amendments of the current SRM list based on new evolving scientific knowledge while ensuring and maintaining a high level of consumer protection.

Specifically, the mandate asked the BIOHAZ panel to evaluate the scientific validity of a report prepared by Det Norske Veritas Ltd" (DNV) for the Swiss Cervelas task force. This report provides an assessment of the current potential human exposure to BSE infectivity that could result from eating sausages made with EU bovine casings. The BIOHAZ panel was further requested to evaluate the conclusions of the DNV report and, if it was considered necessary based on the report and any other new relevant scientific information, to provide a re-assessment of the BSE related risk of bovine intestines after processing into natural sausage casings.

The BIOHAZ panel evaluated the risk assessment as described in the DNV report, and took into account the relevant previous EFSA opinions as well as new scientific data on the same subject.

New but limited experimental scientific data demonstrate that in addition to ileum, also jejunum may harbour infectivity when a large BSE inoculum dose was used to experimentally infect cattle. With regard to the DNV Report, the BIOHAZ Panel considers its approach (concept and methodology) scientifically sound, whereas the interpretation of the results as obtained is not shared by the Panel. Its assumptions were based on limited scientific data obtained from a single morphometric study (which was already found to be inadequate in the previous EFSA Opinion on bovine casings) and on limited and earlier data on the presence of PrPsc/infectivity in bovine gut after experimental oral BSE inoculation. There is uncertainty about the relative BSE risk of neural and lymphoid tissues in casings compared to CNS that might have significant impact on the calculated results of the DNV Report. The Panel notes that the DNV Report considers the individual human BSE exposure risk from bovine casings, excluding ileum, to be "very low". However, when the upper confidence limits are taken into account, along with the uncertainties in key parameter assumptions, the calculated total human exposure per year in the EU from bovine casings, even when ileum is excluded (based on the calculated BSE prevalence in 2007) is 11.000 cattle oral ID50 units per year (when all casings would have been sourced in the UK) and about 1.000 cattle oral ID50 units per year (when all casings would have been sourced in the Netherlands) and therefore cannot be considered negligible. Thus the conclusion in the DNV report that sausage casings sourced from intestines of cattle in EU Member States would lead to a negligible risk for human consumption cannot be considered valid. Moreover, when considering other new relevant scientific information it is concluded that the previous EFSA assessment of the BSE related risk of bovine intestines after processing into natural sausage casings remains valid. The Panel recommends that future considerations on the risk in bovine casings should take into account the BSE prevalence in cattle at that time.

Published: 22 September 2009

http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211902899454.htm?WT.mc_id=EFSAHL01&emt=1


SUMMARY

http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_1317_bovine_intestines_summary_en,0.pdf?ssbinary=true


OPINION

snip...

6. Overview of current scientific knowledge on BSE risk in Bovine Intestines. The previous EFSA Opinion on BSE risk from bovine intestine summarised the scientific knowledge that was available until early 2007. Since then, additional publications have become available on a natural BSE case in Japan (Kimura and Haritani, 2008) and two experimental studies that examined

presence of PrPsc and/or infectivity in the intestines of cattle challenged orally with 100g (Espinosa et al., 2007; Hoffmann et al., 2007). Moreover, a new study performed by the VLA in the UK on PrPsc in BSE-infected cattle (Stack, 2009) and preliminary results from the German BSE pathogenesis study have recently be made available to EFSA and were also taken into account.

6.1. New experimental studies on intestines of BSE infected cattle

Espinosa et al. (2007) examined pooled tissues from 13 cattle inoculated at ages between 4 and 6 months and culled at ages between 24 and 39 months. Infectivity in Tgbov mice but not PrPsc by ELISA/WB was found in Peyer's patches dissected from distal ileum at all ages. Hoffmann et al (2007) demonstrated PrPsc by IHC in Peyer's patches of distal ileum in one of two preclinical animals sacrificed at 24 and 28 months post inoculation (mpi). Most recently, Arnold et al. (2009) estimated the titre of infectivity in the distal ileum from the incubation time found by bioassay in wild type mice. Over time, the infectivity in the distal ileum showed an initial increase up to 14-18 months post exposure, followed by a decrease, which was likely to be highly variable between animals. However, these estimates were based on mouse titration of brain material, while the incubation period to dose relationship may differ between brain and intestines (Robinson et al., 1990).

6.2. Infectivity of intestines in cattle with natural BSE infection

Data on presence of PrPsc or infectivity in intestines of natural BSE cases are sparse. The immunohistochemistry (IHC) and Western blot examinations of three BSE infected cattle detected in Japan in the course of active surveillance (but showing locomotor deficits) found PrPsc in distal ileum of two (by IHC confined to the myenteric plexus) (Iwata et al., 2006). No PrPsc was detected in Peyer's patches of distal ileum, or in samples of other regions of small and large intestine, or in a range of other lymphoid tissues. Labelling of myenteric plexus was also detected in 9/29 confirmed field cases of BSE examined in the UK (Terry et al., 2003). Infectivity by wild-type mouse assay or the presence of PrPsc has not been found in the distal ileum, or other levels of intestine in a total of some six natural BSE cases studied (Fraser and Foster, 1994; Buschmann and Groschup 2005; Iwata et al., 2006). In one of these cases in Germany, however, infectivity was detected in the distal ileum by bioassay in TgBov XV mice (Buschmann and Groschup, 2005). More recently, another BSE case (94 months of age) in Japan showed definite or equivocal immunoreactivity in nerve cells of the myenteric plexus in ileum, caecum and colon, and in Schwann cells of the myenteric plexus in duodenum, jejunum, ileum, caecum and colon (Kimura and Haritani, 2008).

6.3. Study commissioned by ENSCA

This ENSCA commissioned study investigated the presence of BSE PrPsc in small intestines of cattle that had been orally challenged at 4-6 months of age with 100g or 1 g doses of BSE affected brain tissue. These animals were culled and examined 18-30 months post inoculation (p.i.). Three methods to identify PrPsc were applied: a commercial ELISA test, Western immunoblotting, and IHC. Results confirmed previous observations that PrPsc was mainly confined to lymphoid tissue of the ileum, whereas the duodenum was negative and no part of the enteric nervous system tested positive. The lymphoid tissue of the jejunum of one high-dosed animal tested positive. As expected, the low-dosed animals had a much lower frequency of positive ileum samples (1/18 vs. 15/18 in the high-dose group) and some longer incubation times (24 months in the one animal with positive ileum), whereas the high-dose group included animals positive at all ages examined.

As the ENSCA commissioned study was performed retrospectively on archival tissue, sampling was limited by availability, and the study authors themselves concede that "it is possible tissue sampling was not optimal" for duodenum and jejunum of low-dosed animals. The 1g-dosed group included 6 animals sampled at 18 months p.i., 6 at 24 months, and 6 at 30 months. The 100g-dosed group included 6 animals sampled for ileum at 18 months p.i., 6 at 24 months, and 6 at 30 months;

duodenum and jejunum, however, were sampled only in 2 animals each at 18, 24 and 30 months p.i., respectively. From each level of the intestine, three sections were examined by IHC per case. While at least two of the three sections of the ileum per case contained lymphoid follicles, in 36% of the duodenum cases, and in 39% of the jejunum cases lymphoid follicles were absent in any of the examined sections. The frequency of positive follicles per section ranged between 1% and 14% in ileum of the high-dose group, and 0,7% in the one positive ileum of the low-dose group, and was 6,7% and 11,1% in the two positive jejunum sections of one high-dosed animal.

Conclusions on the ENSCA commissioned study:

. This study confirms that detectable PrPsc is mainly confined to lymphoid tissue of the ileum in cattle orally challenged with 100g of BSE brain and culled at 18, 24 and 30 months postinoculation (p.i.)

. One out of 18 animals challenged orally with 1g of BSE brain was positive in ileum.

. One out of 18 animals challenged orally with 100g of BSE brain was positive in jejunum.

. The duodenum was always negative.

. However, the sampling in particular of duodenum and jejunum was limited and contained lymphoid tissue only in a part of sections examined.

. In contrast to previous reports on natural BSE cases in older animals, the enteric nervous system was always negative.

. In consideration of the previous EFSA opinion on bovine intestine that gives detailed advice for future studies, in particular concerning the lower frequency of lymphoid follicles in parts of the intestine other than the distal ileum, the present ENSCA commissioned study meets some but not all recommendations; in particular the mostly negative results obtained for jejunum and duodenum should not be over-interpreted when tissue sampling was limited.

6.4. New preliminary data on bovine intestine from the German BSE Pathogenesis study

In the German BSE pathogenesis study performed at the Friedrich-Loeffler-Institute (FLI), 56 Simmental cross-breed calves aged about four months were challenged orally with 100g brainstemhomogenate pooled out of clinically BSE diseased cattle. The infectivity load in the homogenate was about 106.1 ID50 (grams of tissue)-1 as determined by end-point titration in Tgbov XV mice (Buschmann & Groschup, 2005, Hoffmann et al., 2007). Furthermore, as controls, 18 calves were inoculated orally with a BSE-negative brainstem homogenate. Four to five animals were selected randomly and euthanised every four months. More than 150 tissue and body fluid samples were sampled at subsequent necropsies from each animal under TSE-sterile conditions.

After oral exposure with the TSE agent, previous studies had demonstrated consistently early prion accumulation in the gut associated lymphatic tissue, about six months post infection (mpi) in cattle (Terry et al., 2003), and at two mpi in scrapie infected sheep (van Keulen et al., 2002) and in 21 days old lambs (Andreoletti et al., 2002). In contrast to scrapie, the accumulation of PrPd in the distal ileum of BSE-infected cattle was confined to an only minor proportion of follicles respectively neurons/glial cells of the enteric nervous system (Terry et al., 2003).

Normally when performing IHC, a three micrometer section per paraffin block is used, reflecting a very small proportion of the tissue sample. Therefore a serial section procedure was newly established at the FLI to increase the total amounts of tissue structures examined per sample and consequently increasing the probability of detecting PrPsc accumulation. Thereby, five sections per paraffin block with a plane distance of about 25-30 µm were examined. Hence, a tissue depth of about 150-200 µm per block was screened for positive immunosignals. Additionally two different PrP-specific monoclonal antibodies, highly sensitive for the detection of bovine PrPsc were used.

According to this method, representative samples of the small intestine, in particular Peyer's patches of the distal ileum but also the ileo-caecal junction from most of the infected animals of the German BSE Pathogenesis study were examined by IHC. From 4 mpi until 44 mpi in most animals (38/43), PrPsc was detectable, initially in the follicles of the Peyer's patches and at later stages of the incubation period in the enteric nervous system too.

Conclusions on the German pathogenesis study

. With improved sampling, nearly all animals dosed with 100 g of BSE brain tissue showed PrPsc in distal ileum between 4 and 44 mpi, first in lymphoid tissue and later in enteric nervous system.

7. Review of the DNV report

7.1. Summary of the report

DNV makes an attempt to quantify the amount of BSE infectious load in bovine sausage casings. This is then extrapolated to the risk carried in an individual sausage, a normal persons risk per year and the overall exposure within the EU in a year. The key points of the DNV Report are as follows:

. The DNV Report assumes that the ileum is not used for the production of casings and is removed and discarded.

. The DNV Report is based on the assumption that potential infectivity in bovine intestine used for sausage casing production would be 2 logs less than in the ileum. Based on experimental data, the infectivity in the distal ileum was considered to be at a titre equivalent to that in the CNS at the late stage of infection. Thus infectivity in non-ileal parts of the intestines used for casings production was assumed to be 100 fold less than in the CNS.

. The DNV Report uses a value of 0.43g/m (obtained from Wijnker et al.) of casing to quantify the amount of lymphoid and neural tissue that might harbour infectivity in a sausage casing,

. The results of the DNV Report calculate that an exposure per person per year from bovine casings produced in the Netherlands "would be very low" even when a high consumption pattern like in Germany is assumed (upper range 7 x 10-6 cattle oral (CO) ID50 units). For casings sourced in the UK, the exposure would be about one log higher.

. When the calculated total amount of cumulative human exposure per year in the EU is considered, the following scenario emerges: 11.000 CO ID50 units per year when all casings would have been sourced in the UK, and about 1.000 CO ID50 units when all casings would have been sourced in the Netherlands, a country with an about average prevalence of BSE in the EU4.

4 How can the output of the DNV calculations be interpreted in terms of potential human infections? If we follow, as in the previously adopted EFSA Opinions on Tallow and MBM (EFSA 2005 a and b) the cautionary advice of the original QRA WG and assume the species barrier is 1 as a worst case scenario, then there would be up to 5500 infected person in the EU per year in the first scenario, and up to about 500 in the second. This would have to assume a linear dose-response curve of infectivity at very low doses. If the species barrier was given a more realistic value obtained from the analysis carried out on the exposure of the British population to the BSE agent (EFSA, 2006) of around 1000 - 4000, this would mean that there might be up to around 1 to 5 infected person in the EU per year in the first scenario, and less than 1 in the second.

snip... see full text ;

http://www.efsa.europa.eu/cs/BlobServer/Scientific_Opinion/biohaz_op_1317_bovine_intestines_en,0.pdf?ssbinary=true



----- Original Message -----
From: Terry S. Singeltary Sr.
To: [email protected]
Sent: Wednesday, September 07, 2005 9:44 PM
Subject: Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47


Greetings FDA,



I would kindly like to comment on ;



Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47

SUMMARY: The Food and Drug Administration (FDA) is amending the interim
final rule on use of materials derived from cattle in human food and
cosmetics published in the Federal Register of July 14, 2004. In the
July 14, 2004, interim final rule, FDA designated certain materials
from cattle, including the entire small intestine, as ``prohibited
cattle materials'' and banned the use of such materials in human food,
including dietary supplements, and in cosmetics. FDA is taking this
action in response to comments received on the interim final rule.
Information was provided in comments that persuaded the agency that the
distal ileum, one of three portions of the small intestine, could be
consistently and effectively removed from the small intestine, such
that the remainder of the small intestine, formerly a prohibited cattle
material, could be used for human food or cosmetics. We (FDA) are also
clarifying that milk and milk products, hide and hide-derived products,
and tallow derivatives are not prohibited cattle materials. Comments
also led the agency to reconsider the method cited in the interim final
rule for determining insoluble impurities in tallow and to cite instead
a method that is less costly to use and requires less specialized
equipment. FDA issued the interim final rule to minimize human exposure
to materials that scientific studies have demonstrated are highly
likely to contain the bovine spongiform encephalopathy (BSE) agent in
cattle infected with the disease. FDA believes that the amended
provisions of the interim final rule provide the same level of
protection from human exposure to the agent that causes BSE as the
original provisions. ...



I would kindly like to submit the following ;



I find it very very disturbing that FDA now takes the position;



>>>Information was provided in comments that persuaded the agency that the
distal ileum, one of three portions of the small intestine, could be
consistently and effectively removed from the small intestine, such
that the remainder of the small intestine, formerly a prohibited cattle
material, could be used for human food or cosmetics. <<<



TSE science is emerging and the old testing techniques for TSEs are becoming much more sensitive than when some of these old BSE tissue bio-assays were done in the distant past. I urge once again for the FDA and the USDA to put forth sound science instead of the political and corporate science they have floundered with for the last 3 decades. THERE is much new data out that dispute the position the FDA/USDA have taken on SRMs.



STATEMENT ON INFECTIVITY IN BOVINE TONSIL

snip...end




Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47
Posted Apr 09 2009 7:13pm



http://stanford.wellsphere.com/cjd-article/use-of-materials-derived-from-cattle-in-human-food-and-cosmetics-docket-no-2004n-0081-rin-0910-af47/641209




http://stanford.wellsphere.com/cjd-article/docket-no-03-080-1-usda-issues-proposed-rule-to-allow-live-animal-imports-from-canada/641254




http://cjdmadcowbaseoct2007.blogspot.com/2008/04/use-of-materials-derived-from-cattle-in.html




snip...



2009 UPDATE ON ALABAMA and TEXAS MAD COWS AND FEED THEREFORETO



http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html






snip... see full text;


Wednesday, September 23, 2009
Scientific Opinion on BSE Risk in Bovine Intestines Question number: EFSA-Q-2009-00226


http://bse-atypical.blogspot.com/2009/09/scientific-opinion-on-bse-risk-in.html


TSS
Top