Assessment of the feed additive consisting of Lacticaseibacillus paracasei ATCC PTA-6135 for all animal species for the renewal of its authorisation (Pioneer Hi-Bred International, Inc.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of authorisation of Lacticaseibacillus paracasei ATCC PTA-6135 as a technological additive (functional group: silage additive) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the of authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the active agent L. paracasei ATCC PTA-6135 remains safe for all animal species, consumers and the environment. Regarding user safety, the panel concluded that owing to the nature of the additive, L. paracasei ATCC PTA-6135 should be considered a potential skin and respiratory sensitiser, and any exposure through the skin and respiratory tract is considered a risk. In the absence of data, no conclusion could be drawn on the eye irritation potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Assessment of the feed additive consisting of Lentilactobacillus buchneriATCC PTA-2494 for all animal species for the renewal of its authorisation (Pioneer Hi-Bred International, Inc.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Lentilactobacillus buchneri ATCC PTA-2494 as a technological additive (functional group: silage additives) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the Panel considers that any exposure through skin and respiratory tract is considered a risk. The Panel cannot conclude on the eye irritation potential of the additive due to the lack of data. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Assessment of the feed additive consisting of Limosilactobacillus fermentumNCIMB 30169 for all animal species for the renewal of its authorisation (Microferm Ltd.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application of renewal of Limosilactobacillus fermentum NCIMB 30169 as a technological feed additive (functional group: silage additives) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers, and the environment. Regarding user safety, the additive should be considered a skin and respiratory sensitiser. No conclusions can be drawn on the eye irritancy potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Assessment of the feed additive consisting of Lentilactobacillus buchneriATCC PTA-6138 for all animal species for the renewal of its authorisation (Pioneer Hi-Bred International, Inc.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Lentilactobacillus buchneri ATCC PTA-6138 as a technological additive (functional group: silage additives) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the additive should be considered as a skin and respiratory sensitiser. No conclusions could be drawn on the eye irritancy potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Safety and efficacy of a feed additive consisting of inactivated selenised yeast (Saccharomyces cerevisiae CCTCC M 2022402) for all animal species (Phytobiotics Futterzusatzstoffe GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of the selenised yeast (inactivated) Saccharomyces cerevisiae CCTCC M 2022402 (Plexomin® Se 3000, available in two forms: 'granules' and 'micro') as a nutritional feed additive for all animal species. Based on a tolerance-efficacy trial, the FEEDAP Panel concluded that the additive is safe for chickens for fattening at proposed conditions of use and this conclusion can be extrapolated to all animal species. In the absence of deposition data in all animal species and products, the FEEDAP Panel cannot conclude on the safety for the consumer. Plexomin® Se 3000 (granules) is dust-free; therefore, the exposure through inhalation is unlikely. Plexomin® Se 3000 (micro) presents a risk by inhalation. Both forms of the additive (granules and micro) are considered as respiratory sensitisers. Due to the lack of data, no conclusions can be drawn on the dermal and eye irritation potential of Plexomin® Se 3000 (granules). Plexomin® Se 3000 (micro) is not irritant to the skin and the eyes. No conclusions can be drawn on the potential of both forms of the additive to be dermal sensitisers. The use of the additive in animal nutrition is considered safe for the environment. The additive is an efficacious source of selenium in feedingstuffs for all animal species.

Assessment of the feed additive consisting of Levilactobacillus brevis DSM 21982 for all animal species for the renewal of its authorisation (Marigot Ltd T/A Celtic Sea Minerals).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Levilactobacillus brevis DSM 21982 as a technological feed additive, silage additive, for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The Panel concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the additive should be considered as a skin and respiratory sensitiser. No conclusions can be drawn on the eye irritancy potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Phenomewide Association Study of Health Outcomes Associated With the Genetic Correlates of 25 Hydroxyvitamin D Concentration and Vitamin D Binding Protein Concentration.

While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the GC gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS25OHD, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS25OHD and PGSDBP scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS25OHD was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the GC gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.

Assessment of the feed additive consisting of Enterococcus lactisNCIMB 10415 (Cylactin®) for cats and dogs for the renewal of its authorisation (DSM Nutritional Products Ltd.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of the authorisation of Cylactin® as a zootechnical feed additive for cats and dogs. The active agent of the additive is Enterococcus lactis NCIMB 10415 and the micro-encapsulated formulation, Cylactin® LBC ME5 PET, was assessed. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The Panel concluded that the additive remains safe for cats and dogs. Regarding user safety, the additive was not shown to be skin and eye irritant, but it should be considered a respiratory sensitiser. No conclusions can be drawn on the skin sensitisation. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Assessment of the feed additive consisting of Lentilactobacillus buchneri (formerly Lactobacillus buchneri) NCIMB 30139 for all animal species for the renewal of its authorisation (Volac International Ltd).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Lentilactobacillus buchneri (formerly Lactobacillus buchneri) NCIMB 30139 as a technological additive for use in easy to ensile fresh material for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. There is no new evidence that would lead the FEEDAP Panel to reconsider its previous conclusions. Thus, the Panel concludes that the additive remains safe for all animal species, consumer and the environment under the authorised conditions of use. Regarding user safety, the additive should be considered as a respiratory sensitiser. The additive is not skin irritant, but no conclusions can be drawn on the skin sensitisation or eye irritation potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Cross-ancestry analyses identify new genetic loci associated with 25-hydroxyvitamin D.

Vitamin D status-a complex trait influenced by environmental and genetic factors-is tightly associated with skin colour and ancestry. Yet very few studies have investigated the genetic underpinnings of vitamin D levels across diverse ancestries, and the ones that have, relied on small sample sizes, resulting in inconclusive results. Here, we conduct genome-wide association studies (GWAS) of 25 hydroxyvitamin D (25OHD)-the main circulating form of vitamin D-in 442,435 individuals from four broad genetically-determined ancestry groups represented in the UK Biobank: European (N = 421,867), South Asian (N = 9,983), African (N = 8,306) and East Asian (N = 2,279). We identify a new genetic determinant of 25OHD (rs146759773) in individuals of African ancestry, which was not detected in previous analysis of much larger European cohorts due to low minor allele frequency. We show genome-wide significant evidence of dominance effects in 25OHD that protect against vitamin D deficiency. Given that key events in the synthesis of 25OHD occur in the skin and are affected by pigmentation levels, we conduct GWAS of 25OHD stratified by skin colour and identify new associations. Lastly, we test the interaction between skin colour and variants associated with variance in 25OHD levels and identify two loci (rs10832254 and rs1352846) whose association with 25OHD differs in individuals of distinct complexions. Collectively, our results provide new insights into the complex relationship between 25OHD and skin colour and highlight the importance of diversity in genomic studies. Despite the much larger rates of vitamin D deficiency that we and others report for ancestry groups with dark skin (e.g., South Asian), our study highlights the importance of considering ancestral background and/or skin colour when assessing the implications of low vitamin D.

Safety and efficacy of a feed additive consisting of Weizmannia faecalis DSM 32016 (TechnoSpore50®) for poultry for fattening, poultry reared for laying/breeding, ornamental birds and suckling and weaned Suidae piglets (Biochem Zusatzstoffe Handels- und Produktionsgesellschaft GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Weizmannia faecalis (formerly identified as Bacillus coagulans) DSM 32016 (TechnoSpore50®) as a zootechnical feed additive for poultry reared for breeding/laying/fattening, ornamental birds and suckling and weaned Suidae piglets. The additive is authorised for use in feed for poultry for fattening, ornamental birds and suckling and weaned Suidae piglets. This application sought the extension of use in feed for poultry reared for breeding/laying and the new authorisation in water for drinking for suckling and weaned Suidae piglets, poultry for fattening, reared for breeding/laying and ornamental birds. Moreover, the applicant requested the authorisation of simultaneous use in feed for poultry reared for breeding and laying with coccidiostats. The identity and the lack of toxigenic activity of the active agent was confirmed, and it did not show resistance to relevant antibiotics; therefore, the strain was presumed safe for the target species, consumers and the environment. Since other components did not introduce concerns, TechnoSpore50® was also considered safe for the target species, consumers and the environment. The additive is not a skin/eye irritant but is a respiratory sensitiser. No conclusions could be drawn on the skin sensitisation potential of the additive. TechnoSpore50® was considered to be efficacious in feed for poultry reared for laying/breeding at 1 × 109 CFU/kg and in water for drinking for poultry reared for fattening, poultry reared for laying/breeding, ornamental birds and for suckling and weaned Suidae piglets at 5 × 108 CFU/L. TechnoSpore50® is compatible with halofuginone, diclazuril, monensin sodium, robenidine hydrochloride, salinomycin sodium and monensin sodium + nicarbazin, but not with narasin or narasin + nicarbazin. No conclusions could be drawn on the compatibility of TechnoSpore50® with decoquinate, lasalocid A sodium, semduramicin sodium, nicarbazin or amprolium hydrochloride.

Safety and efficacy of the feed additive consisting of Enterococcus lactisNCIMB 10415 (Cylactin®) for all poultry for fattening or reared for laying/breeding and ornamental birds, all Suidae, calves and other ruminant species for fattening or rearing (DSM Nutritional products Ltd).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of Cylactin® as zootechnical additive. The active agent of the additive is Enterococcus lactis NCIMB 10415, and three additive formulations currently authorised: Cylactin® LBC G35, Cylactin® LBC ME10 and Cylactin® LBC ME20 plus. The additive is currently authorised in the EU for use in poultry (chickens and minor poultry species for fattening, chickens and minor species reared for laying), calves and kids for rearing and for fattening, sows, suckling and weaned piglets and pigs for fattening. The applicant is now seeking the renewal of its authorisation and the extension of use for chickens and minor poultry species reared for breeding, turkeys for fattening and reared for breeding, ornamental birds, lambs for rearing and for fattening, minor or other ruminants' species for rearing and fattening, minor suckling and weaned Suidae species, pigs and minor Suidae species for fattening, rearing or reproduction. In addition, the applicant is seeking authorisation for use in water for drinking for all above-mentioned target species and categories. The applicant has provided evidence that the additive currently on the market complies with the conditions of authorisation. The FEEDAP Panel concludes that the additive is safe for the target animals, consumers and the environment under the authorised/new proposed conditions of use. The Cylactin® LBC ME10 and LBC ME20 plus are not skin and eye irritants, but no conclusion could be drawn on the potential of Cylactin® LBC G35 to be skin and eye irritant. Moreover, no conclusions could be drawn on the additive skin sensitisation potential. The additive is considered a potential respiratory sensitiser. The efficacy for the new target species/categories as well its use in water was extrapolated from the previous efficacy studies.

Assessment of the feed additive consisting of Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) NCIMB 30083 for all animal species for the renewal of its authorisation (Chr. Hansen A/S).

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the assessment of the application for renewal of authorisation of Lactiplantibacillus plantarum (previously Lactobacillus plantarum) NCIMB 30083 as a technological additive, silage additive for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. There is no evidence that would lead the FEEDAP Panel to reconsider its previous conclusions. Thus, the Panel concluded that the additive remains safe for all animal species, consumers and the environment under the authorised conditions of use. Regarding user safety, the additive should be considered as a respiratory sensitiser. No conclusions can be drawn on the skin sensitisation, and skin and eye irritancy potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Efficacy of the feed additives consisting of Enterococcus faecium ATCC 53519 and E. faecium ATCC 55593 for all animal species (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the efficacy of two technological additives consisting of Enterococcus faecium strains ATCC 53519 and ATCC 55593, respectively. The additives are intended for use with all types of fresh materials and for all animal species at a proposed minimum concentration of 1 × 107 colony forming units (CFU) of E. faecium ATCC 53519/kg forage or 5 × 106 CFU of E. faecium ATCC 55593/kg forage. In a previous opinion, the FEEDAP Panel could not conclude on their efficacy since the dry matter content of the ensiled materials at the end of the experiments was not corrected for volatiles, which led to an unreliable estimation of the dry matter loss, and the lack of positive effects on any of the other parameters. The supplementary information submitted by the applicant included updated data on the pH values and the dry matter loss corrected for volatiles. However, the estimation of the dry matter loss corrected for volatiles was wrongly calculated and thus, was not considered for the assessment of the efficacy of the additive. Considering the lack of effect on any other fermentation parameter, the Panel could not conclude on the efficacy of the additive to improve the production of silage under the proposed conditions of use.

Assessment of the feed additive consisting of Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) NCIMB 30084 for all animal species for the renewal of its authorisation (Chr. Hansen A/S).

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on assessment of the application for renewal of authorisation Lactiplantibacillus plantarum (previously Lactobacillus) NCIMB 30084 as a technological feed additive, silage additive for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. There is no new evidence that would lead the FEEDAP Panel to reconsider its previous conclusions. Thus, the Panel concludes that the additive remains safe for all animal species, consumers and the environment under the authorised conditions of use. Regarding user safety, the additive should be considered as a respiratory sensitiser. No conclusions can be drawn on the skin sensitisation, and skin and eye irritancy potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Assessment of the feed additive consisting of Pediococcus pentosaceusNCIMB 30168 for all animal species for the renewal of its authorisation (Volac International Ltd).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Pediococcus pentosaceus NCIMB 30168 as a technological additive for use in forage for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. There is no new evidence that would lead the FEEDAP Panel to reconsider its previous conclusions. Thus, the Panel concludes that the additive remains safe for all animal species, consumers and the environment under the authorised conditions of use. Regarding user safety, the additive should be considered as a respiratory sensitiser. No conclusions can be drawn on the skin sensitisation, and skin and eye irritancy potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Efficacy of a feed additive consisting of Bacillus velezensisNITE BP-01844 (BA-KING®) for chickens for fattening, chickens reared for laying, turkeys for fattening, turkeys reared for breeding and all avian species for fattening, or rearing to slaughter or point of lay including non-food producing species (Toa Biopharma Co., Ltd.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the efficacy of BA-KING® Bacillus velezensis as a zootechnical feed additive to be used as a gut flora stabiliser for chickens for fattening, chickens reared for laying, turkeys for fattening, turkeys reared for breeding and all avian species for fattening or rearing to slaughter or point of lay including non-food producing species. The product under assessment is based on viable spores of a strain identified as B. velezensis, which is considered suitable for the qualified presumption of safety (QPS) approach to safety assessment. In a previous opinion, the FEEDAP Panel concluded that BA-KING® was safe for the target species, consumers of products derived from animals fed the additive and the environment. Additionally, the additive was not irritant to skin but potentially irritant to eyes and respiratory sensitiser. The Panel could not conclude on the efficacy of the additive for the target species at the proposed conditions of use. In the current application, two additional efficacy trials in chickens for fattening were provided. The results showed an improvement in the performance parameters of chickens when supplemented with BA-KING® at 2.0 × 108 CFU/kg complete feed relative to a control group. Considering the previously submitted studies and the newly submitted studies in chickens for fattening, the Panel concluded that BA-KING®, supplemented at 2.0 × 108 CFU/kg complete feed, has the potential to be efficacious in all avian species for fattening or reared for laying/breeding and non-food-producing avian species at the same physiological stage.

Polygenic risk prediction: why and when out-of-sample prediction R2 can exceed SNP-based heritability.

In polygenic score (PGS) analysis, the coefficient of determination (R2) is a key statistic to evaluate efficacy. R2 is the proportion of phenotypic variance explained by the PGS, calculated in a cohort that is independent of the genome-wide association study (GWAS) that provided estimates of allelic effect sizes. The SNP-based heritability (hSNP2, the proportion of total phenotypic variances attributable to all common SNPs) is the theoretical upper limit of the out-of-sample prediction R2. However, in real data analyses R2 has been reported to exceed hSNP2, which occurs in parallel with the observation that hSNP2 estimates tend to decline as the number of cohorts being meta-analyzed increases. Here, we quantify why and when these observations are expected. Using theory and simulation, we show that if heterogeneities in cohort-specific hSNP2 exist, or if genetic correlations between cohorts are less than one, hSNP2 estimates can decrease as the number of cohorts being meta-analyzed increases. We derive conditions when the out-of-sample prediction R2 will be greater than hSNP2 and show the validity of our derivations with real data from a binary trait (major depression) and a continuous trait (educational attainment). Our research calls for a better approach to integrating information from multiple cohorts to address issues of between-cohort heterogeneity.

Safety and efficacy of a feed additive consisting of Lentilactobacillus buchneri DSM 32650 as a feed additive for all animal species (BioCC OÜ).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Lentilactobacillus buchneri DSM 32650 as a technological feed additive (functional group: silage additive) for all animal species. The additive is intended to improve the production of silage at a proposed application rate of 1 × 108 colony-forming units (CFU)/kg fresh material. The bacterial species L. buchneri is considered by the European Food Safety Authority to be suitable for the qualified presumption of safety (QPS) approach. As the identity of the strain has been established and no antimicrobial resistance determinants of concern were detected, the use of the strain as a silage additive is considered safe for the target species, consumers and the environment. In the absence of data, the FEEDAP Panel cannot conclude on the potential of the additive to be a skin/eye irritant or a skin sensitiser. Given the proteinaceous nature of the active agent, the additive should be considered a respiratory sensitiser. The FEEDAP Panel concluded that Lentilactobacillus buchneri DSM 32650 at a minimum concentration of 1 × 108 CFU/kg fresh material may extend the aerobic stability of silage from easy and moderately difficult to ensile fresh material with a dry matter content ranging from 28% to 45%.