Scientific Opinion
Potential BSE risk posed by the use of ruminant collagen and gelatine in feed for non‐ruminant farmed animals
EFSA Panel on Biological Hazards (BIOHAZ) Konstantinos Koutsoumanis Ana Allende Declan Joseph Bolton Sara Bover‐Cid Marianne Chemaly … See all authors
First published: 28 October 2020 https://doi.org/10.2903/j.efsa.2020.6267
Requestor: European Commission
Question number: EFSA‐Q‐2019–00436
Panel members: Ana Allende, Avelino Alvarez‐Ordóñez, Declan Bolton, Sara Bover‐Cid, Marianne Chemaly, Robert Davies, Alessandra De Cesare, Lieve Herman, Friederike Hilbert, Kostas Koutsoumanis, Roland Lindqvist, Maarten Nauta, Luisa Peixe, Giuseppe Ru, Marion Simmons, Panagiotis Skandamis and Elisabetta Suffredini.
Waiver: In accordance with Article 21 of the Decision of the Executive Director on Competing Interest Management a waiver was granted to John Griffin, Working Group member. Pursuant to Article 21(6) of the aforementioned Decision, the concerned expert was allowed to take part in the discussions and in the drafting of the scientific output but was not allowed to be or act as chair, vice‐chair or rapporteur of the Working Group. Any competing interests are recorded in the respective minutes of the meetings of the Working Group, available online: https://www.efsa.europa.eu/sites/default/files/wgs/biological-hazards/wg-ruminant-collagen-gelatine.pdf
Acknowledgements: The Panel wishes to thank Katrin Bote for her contributions to the drafting of this scientific output, and the industry stakeholders that provided information and data: management and members of the Gelatine Manufacturers of Europe (GME), Collagen Casings Trade Association (CCTA); European Feed Manufacturers’ Federation (FEFAC); EU Association of Specialty Feed Ingredients and their Mixtures (FEFANA) and European Former Foodstuff Processors Association (EFFPA).
Adopted: 22 September 2020
Abstract
EFSA was requested to estimate the cattle bovine spongiform encephalopathy (BSE) risk (C‐, L‐ and H‐BSE) posed by ruminant collagen and gelatine produced from raw material fit for human consumption, or from material classified as Category 3 animal by‐products (ABP), to be used in feed intended for non‐ruminant animals, including aquaculture animals. Three risk pathways (RP) were identified by which cattle could be exposed to ruminant feed cross‐contaminated with ruminant collagen or gelatine: 1) recycled former foodstuffs produced in accordance with Regulation (EC) No 853/2004 (RP1), 2) technological or nutritional additives or 3) compound feed, produced either in accordance with Regulation (EC) No 853/2004 (RP2a) or Regulation (EU) No 142/2011 (RP2b). A probabilistic model was developed to estimate the BSE infectivity load measured in cattle oral ID50 (CoID50)/kg, in the gelatine produced from the bones and hide of one infected animal older than 30 months with clinical BSE (worst‐case scenario). The amount of BSE infectivity (50th percentile estimate) in a member state (MS) with negligible risk status was 7.6 × 10–2 CoID50/kg, and 3.1 × 10–4 CoID50/kg in a MS with controlled risk status. The assessment considered the potential contamination pathways and the model results (including uncertainties) regarding the current epidemiological situation in the EU and current statutory controls. Given the estimated amount of BSE infectivity to which cattle would be exposed in a single year, and even if all the estimated undetected BSE cases in the EU were used for the production of collagen or gelatine (either using raw materials fit for human consumption or Category 3 ABP raw materials), it was concluded that the probability that no new case of BSE in the cattle population would be generated through any of the three RP is 99–100% (almost certain).
Summary
In May 2019, the European Food Safety Authority (EFSA) was asked by the European Commission to deliver a scientific opinion on two Terms of Reference (ToRs). ToR1 required an estimate of the cattle bovine spongiform encephalopathy (BSE) risk (C‐, L‐ and H‐BSE) posed by the use of ruminant collagen/gelatine (C&G) produced in accordance with Section XIV and XV of Annex III to Regulation (EC) No 853/2004 in feed intended for non‐ruminant animals including aquaculture animals. ToR2 required an estimate of the cattle BSE risk (C‐, L‐ and H‐BSE) posed by the use of ruminant C&G classified as Category 3 as referred to in Article 10 of Regulation (EC) No 1069/2009 and produced in accordance with Regulation (EU) No 142/2011 for feed intended for non‐ruminant animals including aquaculture animals.
Four assessment questions (AQ) were agreed to address the ToRs. AQ1 – What are the risk pathways for cattle from the use of ruminant C&G in feed for non‐ruminant animals? AQ2 – What is the amount of infectivity in C&G produced from an infected animal at clinical stage? AQ3 – How many infected animals have to be processed and how many kg of C&G have to be produced from infected animals to accumulate 1 cattle oral infectious dose 50 (CoID50)? AQ4 – What is the residual BSE infectivity in the feed at the end of the risk pathways?
A probabilistic model was developed to answer the ToRs. The model estimates the BSE infectivity load, measured in CoID50, contained in the gelatine produced with the bones and hide of one adult animal (i.e. older than 30 months of age), infected with any of the three BSE strains (C, H and L), and at the clinical stage of the disease. The model represents the initial steps in the production chain of gelatine from the point at which an infected animal is slaughtered to the production of gelatine from its bones and hide. Some of the assumptions of the model correspond to worst‐case scenarios and, when data were available, the boundaries of probability distributions in the parameters describing uncertainty were selected to approximate to worst‐case scenarios. As a result, the probability that the infectivity is overestimated by the model is 99–100% (almost certain). The availability of more accurate data on the production of gelatine in terms of yield, infectivity reduction factors and processing methods led to the decision to only develop the model for the production of gelatine. However, some additional scenarios were run for comparison with the production of collagen, applying some assumptions of what is known about collagen production in the European Union (EU).
There are three potential risk pathways associated with the use of ruminant C&G, either produced from animals fit for human consumption or from ABP materials, in feed intended for non‐ruminant animals, including aquaculture animals. Risk pathway 1: C&G produced under Regulation (EC) No 853/2004 and used in former foodstuffs which are then recycled to produce a ‘bread meal’ for animal feed (relevant to ToR1). Risk pathway 2a: C&G produced under Regulation (EC) No 853/2004 and used in feed as technological additive (to encapsulate vitamins) or nutritional additive (supplement for dogs and horses), or as a component of compound feed (relevant to ToR1). Risk pathway 2b: C&G produced under Regulation (EU) No 142/2011 and used in feed as a technological additive (to encapsulate vitamins) or nutritional additive (supplement for dogs and horses), or as a component of compound feed (relevant to ToR2).
According to the results of the model, the 50th percentile of the amount of BSE infectivity per kg of gelatine extracted from the bones and hide of one adult animal with clinical BSE (C, H or L), slaughtered in a MS with negligible risk status, is 7.6 × 10−2 CoID50 (5th–95th percentile: 8 × 10−3–0.8 CoID50), and 3.1 × 10−4 CoID50 (5th–95th percentile: 2.9 × 10−5–4.1 × 10−3 CoID50), in a MS with controlled risk status. For collagen, the estimated amount of infectivity per kg was much lower than for gelatine, i.e. 1.3 × 10−6 (5th–95th percentile: 1.1 × 10−7–1.6 × 10−5 CoID50/kg) in both negligible and controlled risk countries. As a worst‐case scenario, if there was no reduction of BSE infectivity during collagen production, the final amount of infectivity per kg of collagen would be 5 × 10−3 (5th–95th percentile: 3.5 × 10−3–1.8 × 10−2 CoID50/kg), which is still more than 15 times lower than the estimate obtained for gelatine using bones and hides and with a reduction of infectivity during processing in a MS with negligible risk.
The 50th percentile of the number of adult animals with clinical BSE (C, H or L) slaughtered in a MS with negligible risk status that would be required to produce contaminated gelatine containing 1 CoID50, is 1.7 (5th–95th percentile: 0.1–16 infected animals), and 449.8 (5th–95th percentile: 33.8–4,745 infected animals) in a MS with controlled risk status. The 50th percentile of the amount of contaminated gelatine extracted from adult animals with clinical BSE (C, H or L) at clinical stage slaughtered in a MS with negligible risk status that would contain 1 CoID50 is 13.1 kg (5th–95th percentile: 1.2–125.3 kg), and 3,257 (5th–95th percentile: 244.9–34,360 kg) in a MS with controlled risk status. Considering all possible undetected BSE cases in the EU in one single year, estimated by the Cattle TSE Monitoring Model (C‐TSEMM), and the 50th percentile of the total amount of BSE infectivity estimated by the model, the cattle population of the EU would be exposed on average to up to 1.5 × 10−7 CoID50 per animal and per year if all infected animals were slaughtered in MS with negligible risk status and to 6.1 × 10−10 CoID50 if all the infected animals were slaughtered in MS with controlled risk status.
The uncertainties and data gaps in the three risk pathways precluded the execution of a full quantitative assessment of the risk posed through each of the risk pathways. The characterisation of the risk concluded that the probabilities that material from more than one positive animal could be included in the manufacture of any batch of collagen or gelatine and the contamination of ruminant feed with non‐ruminant feed containing C&G on‐farm are both 1–5% (extremely unlikely). Moreover, the final BSE risk to cattle in the three risk pathways is further reduced by additional factors such as the temporal (due to lack of clustering of cases, no multiple cases are slaughtered at the same time) and geographical (the small number of BSE cases that have recently been reported in the EU have been distributed across several countries) distribution of the exposure to any amount of infected material, and the individual host response to exposure. Cattle could be exposed via ruminant feed cross‐contaminated with non‐ruminant feed containing ruminant C&G from a BSE‐infected batch, or by accidental error accessing the wrong feed on farm.
It was concluded that the probability that no new case of BSE in the cattle population would be generated through any of the three risk pathways is 99–100% (almost certain), given the estimated amount of BSE infectivity to which cattle would be exposed.
A number of recommendations have been proposed:
a) to maintain the EU‐wide current surveillance system, to periodically evaluate the new BSE data using epidemiological transmission models and to use the C‐TSEMM model on an annual basis with updated data in order to monitor the ability of the current surveillance system to detect BSE at both MS and EU level;
b) to evaluate the impact of the specific industrial processes for the production of collagen and gelatine on the infectivity of naturally occurring BSE agents;
c) to undertake research activities aimed at the production of new data regarding the susceptibility of cattle to infection with H‐BSE or L‐BSE via the oral route, and the quantitative distribution of infectivity in tissues of cattle preclinically and clinically affected with H‐ and L‐BSE;
d) to produce new data measuring the reduction factors for cattle BSE infectivity provided by a variety of standard processing methods.
1 Introduction
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3.3.4 Concluding remarks to Sections 3.1, 3.2 and 3.3 Collagen is a protein‐based product derived from the hides, skins, bones, tendons and sinews of animals. Gelatine is a natural, soluble protein, obtained by the partial hydrolysis of collagen produced from the bones, hides and skins, tendons and sinews of animals. Approximately 25% of the gelatine produced in the EU is made from bovine raw materials (the rest being mostly of porcine origin, or from fish). Commission Regulation (EC) No 142/2011 for ABPs and Regulation (EC) No 853/2004 for foodstuff define C&G and specify the authorised material from which C&G are produced and the methods to produce them. Both Commission Regulation (EC) No 142/2011 and Regulation (EC) No 853/2004 allow flexibility in relation to the processes used for the production of C&G, resulting in a variety of industrial processes being used. This fact presents challenges in determining the effect of these processes in reducing any BSE infectivity that may be present in the raw materials, as for example: –There are various manufacturing processes for extracting collagen from hides, depending on the raw material used and the desired function of the final collagen product. –For collagen production, pretreatments may involve harsh acidic or alkaline treatments, and solvents may also be used before extraction of the collagen by chemical or enzymatic hydrolysis. –Gelatine manufacturing, which uses both hides and bones, is less variable and raw materials are crushed or chopped, washed and then treated with acid or alkali before the gelatine is extracted using water, then filtered and sterilised. 3.4 TSE infectivity: tissue distribution and calculation of infectious titre The known bovine TSE agents replicate and accumulate in the central nervous system (CNS) and can disseminate along the nerves of the peripheral (autonomic and motor) nervous system. However, in a given host, the agent distribution and the level of infectivity in other tissues (relative to the brain) can vary substantially depending on the TSE strain and the stage of the incubation period (IP) (Arnold et al., 2007). When prion protein (PrP) distribution within tissues has been visualised by immunochemical methods, it is apparent that the visible accumulation of disease‐associated PrP is usually localised in those structures associated with the nervous or lymphatic systems (e.g. muscle spindles within muscle, and the autonomic ganglia and gut‐associated lymphoid tissue (GALT) in the digestive tract).
The limited data on tissue positivity are generally based on the presence/absence of detectable PrP rather than the direct demonstration of infectivity, and even when infectivity has been directly measured this too tends to be a single assay to establish the presence/absence of infectivity rather than an end‐point titration, although an estimation of titre can be calculated from such data (for full discussion of such methods, see EFSA, 2014). Where infectivity titres have been established/estimated, these titres are not absolute, because they are specific for the model used (e.g. conventional mice, cattle or bovinised transgenic mice), but some parallel titration studies have enabled conversion factors to be proposed (see Appendix B and EFSA, 2014). Failure to detect infectivity in a bioassay means that the tissue being tested is either negative, or that infectivity is below the limit of detection of the model (a threshold that will vary depending on the model used).
3.4.1 Classical BSE The specified risk materials (SRM) listed in Regulation (EC) No 999/2001 are tissues that contain the highest infectious loads in cattle with classical BSE. Not all tissues with the potential to contain infectivity are included in this list. The current SRM definition is as follows: The skull excluding the mandible and including the brain and eyes, and the spinal cord of animals aged over 12 months. The vertebral column excluding the vertebrae of the tail, the spinous and transverse processes of the cervical, thoracic and lumbar vertebrae and the median sacral crest and wings of the sacrum, but including the DRG, of animals aged over 30 months, from animals whose origin is in a MS or non‐EU country or one of their regions with a controlled or undetermined BSE risk. The tonsils, the last 4 m of the small intestine, the caecum and the mesentery from animals of all ages whose origin is in a MS or non‐EU country or one of their regions with a controlled or undetermined BSE risk. 3.4.2 Atypical BSE In both H‐BSE and L‐BSE, disease‐related PrP accumulation has been reported consistently in CNS tissues, peripheral ganglia and nerves, muscles (predominantly the muscle spindles), adrenal glands and retina. All these tissues are also positive in C‐BSE. By contrast with C‐BSE, no lymphoid tissues or gastrointestinal tissues from H‐BSE‐ or L‐BSE‐affected animals have tested positive for the presence of disease‐specific PrP (by immunohistochemistry or western blot) or infectivity (bioassay).
The current lack of information on the possible presence or distribution of infectivity in tissues of atypical BSE‐infected cattle does not allow judgement of whether the current list of bovine SRM (see above) is fit for purpose for atypical BSE carcasses. Where data exist from both field cases and experimental animals (i.e. for L‐BSE only), there is good agreement of the data on abnormal PrP distribution (see EFSA, 2014, for review), but there are no quantitative data for infectivity. There are no data for field cases of H‐BSE.
3.4.3 BSE infectivity in hides, skins and bones The number of studies providing data on potential tissue infectivity in bovine hides, skin and bones is very small and much of this seminal work, all of which relates to C‐BSE specifically, was undertaken before the development of transgenic mouse models. Most data come from a small number of natural cases and pathogenesis studies in the UK (Wells et al., 1998, 1999).
In the UK study, cattle were orally challenged with 100 g of C‐BSE‐infected brain tissues and tissues were harvested at various time points post challenge for bioassay in conventional mice (Wells et al., 1998, 1999; Arnold et al., 2009). Each inoculum was made by pooling the tissue samples from each of the animals killed at the same time point (maximum n = 4). Infectivity was reported in sternal bone marrow from animals near the clinical end‐point. No bioassays were performed on skin or compact bone.
Subsequent bioassays in cattle of tissue from these same experimentally challenged animals did not identify infectivity in bone marrow (Sohn et al., 2009). Bones were not tested. These negative results were interpreted as representing maximum hypothetical levels of infectivity of less than 0.1 cattle intracerebral (i.c.) ID50/g, which is beyond the end point of detection of the assay. Due to the small group size of four animals in that titration study, this estimate must be regarded as an upper limit that equates to 10–6 cattle oral ID50 per gram (CoID50/g) (Sohn et al., 2009).
A similar figure was obtained for skin in the UK pathogenesis study, in which cattle bioassays of skin were also negative.4 The analysis of these survival periods using a Poisson model for limiting dilution and applying the cattle i.c. to cattle oral conversion factor (see Appendix B) showed that skin could contain up to 10−6.1 CoID50/g (upper limit of the 95% confidence interval).
In the context of this risk assessment, the amount of infectivity in both bone marrow and hide included in the probabilistic model has been fixed at 10–6 CoID50/g. However, in natural disease, no infectivity has been detected in bone marrow or skin (SSC, 2002), so these calculated maximum infectivity levels represent a hypothetical worst‐case scenario. Compact bone has never been tested.
In a German pathogenesis study (Hoffmann et al., 2007), the bioassay was not used to test for infectivity, but immunohistochemistry and western blotting were applied to look for PrP accumulation as a marker of disease. Bone marrow was negative. Skin and bones were not tested.
Although various more recent studies have used the tissue distribution of PrP as a marker for possible infectivity in atypical BSE (see EFSA, 2014, for an exhaustive list), there are no data available on infectivity in bones, skins or hides for either H‐ or L‐BSE. Again, there is no evidence of infectivity in bones, skins or hides.
However, some positive tissues from within the same animal have the potential to cross‐contaminate these raw materials during their collection at slaughtering (see Section 3.6.1).
3.5 Inactivation of prions during the processing of raw materials for the production of C&G
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3.6.5 Concluding remarks to Sections 3.4, 3.5 and 3.6
No infectivity or disease‐related PrP accumulation has ever been recorded in cattle skin or bones – the tissues used as raw material for the production of C&G. However, under the worst‐case scenario (based on the sensitivity limits of infectivity assays that gave negative results), the infectivity both in bone marrow and in hide included in the probabilistic model has been fixed at 10−6 CoID50/gram.
All quantitative data on BSE infectivity in tissues are derived from studies on C‐BSE. No equivalent data exist for H‐BSE or L‐BSE.
There is no comprehensive experimental study regarding the inactivation or reduction in infectivity of cattle C‐BSE, H‐BSE or L‐BSE prions associated with industrial gelatine or collagen manufacturing steps or processes. Most published data on the inactivation of prions by processing methods representative of those prevailing during C&G production have been derived from mouse‐adapted TSE strains, not naturally occurring BSE. When necessary, data derived from inactivation studies on rodent‐adapted TSE strains have been considered by the WG to parameterise the probabilistic model (Section 3.7).
Available data support the view that the industrial processes used to produce C&G have the capacity to reduce the TSE infectivity that could be present in the raw materials.
It cannot be assumed that log reductions achieved by each step individually will necessarily add up to provide a realistic total RF estimate, given the changes to the physicochemical composition of the infectious agent that might occur during such processes.
Data on prion inactivation by gelatine manufacturing steps (excluding the UHT final sterilisation step), obtained using rodent‐adapted prions, indicate that strong acidic treatments, used on bones, provide RF ranging from 1.17 log10 to 3.7 log10, whereas strong alkaline treatments, used on hides, provide RF ranging from 2.1 log10 to 5.25 log10.
C‐BSE, H‐BSE and L‐BSE infectivity RF achieved by gelatine manufacturing steps could differ from those observed for rodent‐adapted strains, between each other and according to the exact nature of the applied industrial processes.
Cross‐contamination of bones and hides with brain, spinal cord and DRG can occur during slaughter and carcass dressing. Further cross‐contamination of bones and hides can also occur during transport, storage and processing in intermediate plants.
Although there is a greater potential possibility of cross‐contamination in Category 3 raw materials than in those deemed fit for human consumption, the probability that the level of infectivity, in terms of the CoID50 units, in the raw materials that would be used in the production of collagen/gelatine under the ABP Regulations would be different to that in the materials that would be used for the production of collagen/gelatine under the Regulation (EC) No 853/2004 is considered to be 1–5% (extremely unlikely).
The process for C&G production under the ABP Regulations is essentially the same as that under Regulation (EC) No 853/2004. Therefore, it can be assumed that the reduction of the BSE infectivity measured in CoID50 per kg caused by the processing of raw materials to produce collagen/gelatine under the ABP Regulations would be of a similar level as that produced under the Regulation (EC) No 853/2004.
3.7 QRA of the residual BSE infectivity in gelatine
3.7.1 Model structure
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3.10.3 Cross‐contamination of ruminant feed with non‐ruminant feed As set out in Section B of Annex IV of EU Regulation No 999/2001, compound feed intended for non‐ruminant farmed animals shall be produced in establishments that do not produce compound feed for ruminants. By way of a derogation from this, the production of compound feed for non‐ruminants in feed mills that also produce compound feed for ruminants may be permitted by the competent authority if the manufacturing, storage, transport and packaging of the ruminant and non‐ruminant feed is completely separate. The manufacturers are obliged to keep detailed records of the purchase of the ABP used in these premises for at least 5 years. They are also obliged to carry out regular testing of the compound feed intended for ruminants to verify the absence of unauthorised constituents of animal origin.
In addition to EU Regulation No 999/2001, there are several other Regulations in force to monitor the feed chain for compliance with the feed ban (Commission Regulation No 51/2013 and Commission Regulation (EC) No 691/2013 amending Regulation (EC) No 152/2009). The correct application of such Regulations would in principle allow the detection of cross‐contamination events.
Despite these regulatory requirements, cross‐contamination of ruminant feed with non‐ruminant feed could occur both at feed mill level and at farm level (AFSSA, 2001). Some mixed feed mills produce feed for both monogastric and ruminant species and are potentially vulnerable to cross‐contamination events, even when completely separate processing lines are used, as the EU Regulation requires. In addition, the specialisation of feed mills is not an economically feasible option in some countries or regions with low animal density (Ducrot et al., 2013).
Overall, the probability of contamination of ruminant feed with non‐ruminant feed containing collagen or gelatine at feed mills is considered to be 1–5% (extremely unlikely), and if it occurred, the amount of cross‐contaminated material would be extremely low, as there will be a considerable dilution of any BSE‐infected collagen or gelatine due to mixing with other feed materials in the production of animal feed.
3.10.4 Exposure of cattle to BSE infectivity and final risk The feeding of cattle with ruminant feed cross‐contaminated during production by non‐ruminant feed containing collagen or gelatine (Figure 10) is not the only exposure route. As explained in the EFSA Opinion on the QRA of the BSE risk posed by PAP (EFSA BIOHAZ Panel, 2018), farms with mixed species may take delivery of compound feeds for different species (or mix their own). Contamination could possible occur through deliberate or accidental feeding of the wrong food by the farmer, inappropriate storage of feeds (e.g. poor segregation), or poor facilities, which could lead, for example, to animal breakouts, giving cattle access to the wrong feed.
Under Section B of Annex IV of EU Regulation No 999/2001, the use of compound feed containing ABPs, such as fishmeal, that is currently permitted in non‐ruminant feed, is only allowed on farms where only non‐ruminants are kept. Moreover, home compounders using such feed must be registered with the competent authority. Due to these requirements, the contamination of ruminant feed with non‐ruminant feed containing collagen or gelatine on farm is also considered to be 1–5% (extremely unlikely).
Cattle gaining accidental access to pet food containing collagen or gelatine could be another example of this route of exposure. However, while feed for different farmed animals (e.g. pigs and cattle) are likely to be stored close to each other on the same premises, pet food is likely to be stored and handled separately. Pets are more likely to share the same environment as the human residents, rather than that of the farmed animals, which are usually well confined.
If any batch of animal feed containing BSE infectivity, due to cross‐contamination or error, is consumed by cattle, it would be consumed by a number of animals rather than one, therefore reducing the possibility that an infectious dose would be consumed by a single animal.
As stated in Section 3.8.2, under the worst‐case scenario of all the BSE cases in the EU in 1 year being devoted to the production of collagen or gelatine, and cattle being exposed to all of the resulting infectivity, the threshold to generate one new case of BSE in the EU cattle population in a single year would not be exceeded.
The final BSE risk to cattle via any of the three RP detailed in the previous sections is affected by additional factors such as the temporal (due to lack of clustering of cases, no multiple cattle are slaughtered at the same time) and geographical (multiple countries report cases of BSE in the EU) distribution of the exposure to the entire amount of infected material, and the individual host response to exposure, that will also affect the outcome.
Finally, as described earlier, the dilution of collagen or gelatine containing BSE infectivity also plays a significant role, as only a fraction produced from one or all infected animal/s in the EU would be part of the same batch of feed for non‐ruminants and only a very small proportion of the feed for non‐ruminants could cross‐contaminate a batch of ruminant feed.
In summary, if ruminant feed was cross‐contaminated with non‐ruminant feed containing ruminant collagen or gelatine from a BSE‐infected batch, either as former foodstuffs recycled for animal feed produced under Regulation (EC) No 853/2004, or as additives or as a protein source, produced under Regulation (EC) No 853/2004 or under Regulation (EC) No 142/2011, the probability that no new case of BSE in the cattle population would be generated through any of the three risk pathways is 99‐100% (almost certain), given the estimated amount of BSE infectivity to which cattle would be exposed.
3.10.5 Concluding remarks for Sections 3.7, 3.8, 3.9 and 3.10
A probabilistic model was developed to assess a worst‐case scenario in which one adult BSE‐infected animal older than 30 months of age at clinical end‐stage escapes on‐farm and slaughterhouse detection by the surveillance system (clinical suspect or fallen stock) and is consequently slaughtered and its bones and hide used to produce gelatine.
In the model, it is assumed that the infectivity contained in raw bones and hide come from the intrinsic infectivity contained in the target tissues, and from cross‐contamination by other tissues, from the same animal, during slaughter and processing.
The model produces two different sets of outputs depending on the BSE risk status (negligible vs controlled) of the MS. A different list of SRM in the two situations may affect the residual amount of potential for cross‐contamination. As an example, for controlled risk countries, the removal of the vertebral column implies the removal of a substantial amount of infectivity.
Some of the assumptions of the model correspond to worst‐case scenarios, and when data were available, the boundaries of probability distributions in the parameters describing uncertainty were selected to approximate to worst‐case scenarios. As a result, the model overestimates the actual amount of infectivity per kg of gelatine produced from an infected animal.
Based on the model, in a negligible risk country the estimates for the three outputs were respectively: 7.6 × 10−2 CoID50/kg gelatine (5th–95th percentile: 8 × 10−3–0.8 CoID50/kg); 1.7 infected animals needed to reach 1 CoID50 (5th–95th percentile: 0.1–16 infected animals); and 13.1 kg of gelatine from infected animals needed to reach 1 CoID50 (5th–95th percentile: 1.2–125.3 kg).
The corresponding figures in a controlled risk country were respectively: 3.1 × 10−4 CoID50/kg (5th–95th percentile: 2.9 × 10−5–4.1 × 10−3 CoID50/kg); 449.8 infected animals (5th–95th percentile: 33.8–4,745 infected animals); and 3,257 kg (5th–95th percentile: 244.9–34,360 kg). The sensitivity analysis showed that the parameters ‘BSE infectivity in spinal cord and DRG per g’ and ‘Reduction of infectivity due to the processing of bones’ were the parameters that most affected the outputs of the model.
The current occurrence of any form of BSE in the EU is extremely low and the number of infected cattle that may go undetected each year is estimated to be equal to 11.4 (2.75th–97.5th percentiles: 3.6–19.8). If all the undetected BSE cases in the EU in a single year contributed raw material to the production of gelatine, the 50th percentile of the total infectivity in the gelatine obtained would be 6.3 CoID50 and 2.6 × 10−2 CoID50, if the animals were slaughtered in negligible or controlled risk countries, respectively.
At individual animal level, the consequences of exposure to the maximum amount of BSE infectivity produced in the EU in a single year via C&G are difficult to predict. Applying a linear dose response at low dose levels the average amount of infectivity to which every individual in the 42 million cattle in the EU would be exposed to in one single year would be below a previously estimated threshold of 10−7 CoID50/animal per year, required to generate a new case of BSE.
Once the C&G have been produced, if ruminant C&G (produced from animals fit for human consumption or ABP) are authorised for inclusion in feed for non‐ruminants, including aquaculture animals, there are three potential RPs identified from their use: two apply to C&G produced under the Regulation (EC) No 853/2004 and used in foodstuffs (relevant to ToR1) or in feed (relevant to ToR1); the third one refers to C&G produced under the Regulation (EU) No 142/2011 and used in feed (relevant to ToR2).
There are data gaps and uncertainties in relation to several of the factors characterising the three RPs, mainly on how the C&G is or would be used in feed, which preclude the execution of a full quantitative assessment of the risk posed by the entire RP.
The dilution effect of one infected animal in a batch of gelatine was estimated within the outputs of the model, showing that the residual infectivity per kg of gelatine in the batch would be extremely low, either if produced from hides only or from bones only, or both.
The last steps in the RP make it evident that an additional dilution effect of any residual infectivity from C&G included into non‐ruminant feed will occur through the potential cross‐contamination of ruminant feed.
Finally, the BSE risk to cattle through exposure to any residual BSE‐infectivity in feed will be also affected by additional factors such as the geographical and temporal distribution of cattle exposure to the entire infected material, as well as the individual host response to exposure to BSE infectivity. Overall, it was concluded that the probability that no new case of BSE in the cattle population would be generated through any of the three RPs is 99‐100% (almost certain), given the estimated amount of BSE infectivity to which cattle would be exposed.
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5 Recommendations
The BSE risk posed by the use of ruminant C&G in feed directly depends on the prevalence of the BSE agents (C‐BSE, H‐BSE and L‐BSE) in the cattle population. It is recommended:
–to maintain the current EU‐wide surveillance system in order to: (1) monitor the final stages of the BSE epidemic; (2) detect a potential re‐emergence of BSE; and (3) detect new BSE forms in cattle, should they appear.
–to use the C‐TSEMM model on an annual basis with updated data in order to monitor the ability of the current surveillance system to detect BSE at both MS and EU level.
To evaluate the impact of the specific industrial processes employed by the industry for the production of C&G on the infectivity of naturally occurring BSE agents. In particular, to undertake research activities aimed at the production of new data measuring the sensitivity/resistance of cattle BSE agents (C‐, H‐ and L‐BSE independently, but in parallel) to a variety of standard processing methods (e.g. acid and alkaline treatments and heat), and, when possible, to specifically quantify the RF achievable.
To undertake research activities aimed at the production of new data regarding the susceptibility of cattle to infection with H‐BSE or L‐BSE via the oral route, and the quantitative distribution of infectivity in tissues of cattle preclinically and clinically affected with H‐ and L‐BSE. The current lack of such data poses a major limitation for the assessment of the probability of exposure to prion disease associated with the use of cattle‐derived materials in food and feed.
To periodically reassess the risks addressed in this opinion, should the current ban be lifted in the future, therefore changing the relative plausibility and likelihood of RP 1, 2a and 2b.
WEDNESDAY, OCTOBER 28, 2020
EFSA Annual report of the Scientific Network on BSE-TSE 2020 Singeltary Submission
Terry S. Singeltary Sr.
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