Assessment of the feed additive beta‐carotene (3a160(a)) for all animal species for the renewal of its authorisation (BASF SE, DSM Nutritional Products Ltd., Europe‐Asia GmbH, JYB Europe BV, NHU Europe GmbH)
Roberto Edoardo Villa, Giovanna Azimonti, Eleftherios Bonos, Henrik Christensen, Mojca Durjava, Birgit Dusemund, Ronette Gehring, Boet Glandorf, Maryline Kouba, Marta López‐Alonso, Francesca Marcon, Carlo Nebbia, Alena Pechová, Miguel Prieto‐Maradona, Ilen Röhe
TL;DR
This paper assesses the safety and efficacy of beta-carotene as a feed additive for all animal species, confirming its safety for animals, consumers, and the environment.
Contribution
The study confirms the continued safety of beta-carotene in animal feed under approved conditions for renewal of its authorisation.
Findings
Beta-carotene is safe for target species, consumers, and the environment.
It is not a skin or eye irritant and not a skin sensitiser.
No efficacy assessment is needed for renewal of its authorisation.
Abstract
Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of beta‐carotene (3a160(a)) for the renewal of its authorisation as a nutritional additive for all animal species. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the use of beta‐carotene in animal nutrition under the approved conditions remains safe for target species, consumers and the environment. Regarding user safety, the FEEDAP Panel concludes that beta‐carotene is not a skin and eye irritant and not a skin sensitiser. One preparation containing 10% beta‐carotene was shown not to be a skin sensitiser. However, no conclusions on the safety for the user can be done on any other preparations. The Panel concluded there is no need for assessing the efficacy of the additive in the context of the renewal of the…
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| Company A | Company B | Company C | Company D | Company E | |
|---|---|---|---|---|---|
|
| |||||
| Total colouring matters (dried substance) expressed as beta‐carotene (%) | ≥ 96 | ≥ 96 | ≥ 96 | ≥ 96 | ≥ 96 |
| Carotenoids other than beta‐carotene (% of total colouring matters) | ≤ 3 | ≤ 3 | ≤ 3 | ≤ 3 | ≤ 3 |
|
| [5] | [10] | [5] | [5] | [5] |
| Total colouring matters (dried substance) expressed as beta‐carotene | 99.7 (98.7–100.3) | 100.1 (98.4–100.9) | 96.7 (96.2–97.2) | 100.2 (100–100.4) | 98.2 (97.8–98.9) |
| Carotenoids other than beta‐carotene | 1.22 (0.8–1.6) | 0.08 (0–0.15) [5] | 1.96 (1.8–2.0) | 0.48 (0.40–0.60) | 1 |
| Loss on drying (%) | 0.06 (0.05–0.08) | 0.1 (0–0.2) | – | 0.014 (0.01–0.03) | ≤ 0.1 |
| Residue on ignition (%) | – | – | 0.12–0.2 | 0.01–0.1 | < 0.05 |
|
| [5] | [5] | [5] | [5] | |
| Triphenylphosphine oxide (TPPO) | 19–55 | 18–44.90 [10] | 94–99 | – | 35–60 |
| Lead | < 2 | ≤ 0.1 [3] | 0.1–1.1 |
| < 0.5 |
| Mercury | < 0.001 | ≤ 0.01 [3] | 0.02–0.05 |
| < 0.03 |
| Cadmium | < 0.001 | ≤ 0.1 [3] | 0.05–0.09 |
| < 0.5 |
| Arsenic | < 0.01 | ≤ 0.1 [3] | 0.4–0.6 |
| < 0.5 |
| C25 Aldehyde | – | 551–971 [10] | – | – | – |
| Impurity G (Area‐%) | – | – | – | – | 0.1 |
| Impurity H (Area‐%) | – | – | – | – | 0.3 |
|
| [10] | [5] | [3] | [5] | |
| Dichloromethane | 20–84 [5] | 24–326 | – | 36–110 | – |
| Methanol | 16–37 [3] | <30 | – | – | <30–40 |
| Ethanol | 652–719 [3] | – | 1104–1205 | – | – |
| Acetone | 1342–1782 [3] | 1364–2024 | ‐ | 391–576 | 930–1500 |
| Methylbenzene | – | – | – | < 22.3 | – |
| Ethyl acetate | – | – | – | 306–405 | – |
| Isobutanol | – | – | – | < 50 | 180–240 |
| Heptane | – | – | – | – | 1100–1300 |
| ■■■■■ | – | 0.11–0.44 [6] | – | – | – |
| ■■■■■ | – | 1.02–1.77 [6] | – | – | – |
|
| |||||
| 5°C ± 2°C – 12 months | 99.7 | – | – | – | – |
| 40°C ± 2°C – 6 months | 98.2 | – | – | – | – |
| 25°C/ 60%RH – 24 months | – | – | – | – | 99.9 |
| Company A | Company B | Company C | Company D | Company E | |
|---|---|---|---|---|---|
|
| |||||
| Beta‐carotene (%) | ≥ 10 | ≥ 10 | ≥ 10 | ≥ 10 | ≥ 10 |
| Triphenylphosphane (TPPO, mg/kg) | ≤ 100 | ≤ 100 | ≤ 100 | ≤ 100 | ≤ 100 |
|
| [5] | [5] | [5] | [5] | [5] |
| Beta‐carotene (%) | 10.9 (10.8–11) | 10.8 (10–11) | 11 (10.9–11.1) | 12.6 (12–13.5) | 10.2 (10.1–10.4) |
| Loss on drying (%) | 4.4–5.1 | 5–6 | 6.2–6.8 | 4.2–4.8 | – |
|
| [3] | [5] | [5] | [3] | |
| Triphenylphosphine oxide (TPPO) | < 5–6 [3] |
| 21–37 | – | < 20 |
| Lead | 0.031–2 [8] | < 2 | 0.5–0.7 | < 0.5 | < 0.5 |
| Mercury | < 0.1 [8] | < 0.1 | 0.01–0.02 | – | < 0.02 |
| Cadmium | < 0.1 [8] | < 1 | 0.03–0.04 | – | < 0.2 |
| Arsenic | < 0.04–2 [8] | < 3 | 0.4–0.6 | – | < 0.5 |
|
| [3] | [3] | |||
| PCDD/Fs (ng WHO2005‐TEQ/kg) | 0.0568–0.0574 | – | – | – | 0.15–0.16 |
| PCDD/Fs + PCBs (ng WHO2005‐TEQ/kg) | 0.1161–0.1166 | – | – | – | 0.28 |
| nDL‐PCBs (μg/kg) | 0.53 | – | – | – | 1.59 |
|
| [3] | [3] | |||
| Aflatoxin B1 | < 0.2 | – | – | – | < 3 |
| Aflatoxin B2 | < 0.2 | – | – | – | – |
| Aflatoxins G1 + G2 | < 0.2 | – | – | – | – |
| Deoxynivalenol (DON) | < 10 | – | – | – | < 500 |
| Ochratoxin A | – | < 5 | |||
| Zearalenone | < 5 | – | – | – | < 50 |
| Fumonisin B1 and B2 | < 50 | – | – | – | < 200 |
|
| |||||
| Dichloromethane | 28–43 [5] | <1 [3] | 17–52 [5] | – | – |
|
| [3] | [3] | |||
| Salmonella spp. (per 25 g) | Not detected | – | – |
| Not detected |
|
| < 10 | – | – | – |
|
|
| Not detected | – | – | – | < 1 cfu/g [1] |
| Yeast and moulds (CFU/g) | < 100 | – | – |
| – |
| Company A | Company B | Company C | Company D | Company E | |
|---|---|---|---|---|---|
|
| |||||
|
| Solid | Solid | Solid | Solid | Solid |
| Loose density (kg/m3) | – | 560–570 [3] | – | – | – |
| Tapped density (kg/m3) | – | 640–660 [3] | – | – | – |
| Dusting potential (Stauber Heubach) (mg/m3) | 433 [1] | 200–400 [2] | 164 [1] | 564 [1] | 2220–3305 [3] |
| Particle size distribution (laser diffraction) | |||||
| 150 μm (% of particles below, v/v) | – | 1–3 [3] | – | – | – |
| 53 μm (% of particles below, v/v) | – | 0 [3] | – | – | – |
| Dv (10), μm | 170–186 [3] | – | 164.4 [1] | 255.7 [1] | 177.8–196.6 [3] |
| Dv (50), μm | 268–279 [3] | – | 263.1 [1] | 435 [1] | 290–318.4 [3] |
| Dv (90), μm | 387–438 [3] | – | 410.3 [1] | 712.6 [1] | 486–450 [3] |
|
| |||||
|
| [3] | [3] | [3] | [3] | |
| 25°C/60% RH | 97.3–98.2 | 96–99 | 97.6–97.8 [3] | 97.7–100 | 97–100 |
| 40°C/75% RH – 6 months | 98.19–98.26 | 95–102 | 98.69 [1] | – | – |
| 15°C – 24 months (Comp B) or 30 months (Comp E) | – | 93–98 | – | – | 96–100 |
|
| [2] | ||||
| Broiler premix | – | 70–75 | – | – | – |
| 25°C – 6 months | |||||
| Mineral premix 25°C – 6 months (Comp B), 30 weeks (Comp E) | – | 89–97 | – | – | 35–44 [3] |
| Standard mineral broiler premix: 30°C/75% RH 30 weeks | – | – | – | – | 0 [3] |
|
| [3] | ||||
| Chickens for fattening | |||||
| Pelleting: 80°C (broiler feed) | – | 100–118 [3] | – | – | – |
| Pelleted: 80°C, 3 months | – | 61–88 [3] | – | – | – |
| Mash: 25°C/60% RH, 16 weeks | – | – | – | – | 57–76 |
| Mash: 30°C/75% RH, 16 weeks | – | – | – | – | 40–50 |
| Pigs for fattening | |||||
| Pelleting: 80°C | – | – | – | – | 100 |
| Pelleted: 25°C/60% RH, 16 weeks | – | – | – | – | 36–44 |
| Pelleted: 30°C/75% RH, 16 weeks | – | – | – | – | 18–19 |
| Ruminant feed | – | 106 [1] | – | – | – |
| Pelleting: 80°C | |||||
| Shrimp diet | |||||
| Extrudates: 25°C/60% RH, 16 weeks | – | – | – | – | 87 |
| Extrudates: 30°C/75% RH, 16 weeks | – | – | – | – | 81–82 |
| Extrusion: 100°C | – | – | – | – | 93.5–80.3 |
|
| [3] | ||||
| Broiler feed‐mash | – | – | – | – | 7–9.4 |
| Pig feed‐pelleted | – | – | – | – | 3.5–5.3 |
| Shrimp feed‐extrudates | – | – | – | – | 2.1–3.8 |
| Animal products | mg/kg wet tissue/products | Reference |
|---|---|---|
| Birds' liver | 2.3 | Miao et al. ( |
| Mammals' fat tissue | 1.29 | Jin et al. ( |
| Mammals' liver | 7.43 | Jin et al. ( |
| Mammals' meat | 0.41 | Jin et al. ( |
| Milk | 0.204 | EFSA FEEDAP Panel ( |
| Whole eggs | 0.53 | Miao et al. ( |
| Population class | Maximum HRP (mg/kg bw per day) | Default body weight (EFSA Scientific Committee, | Maximum HRP (mg/day) |
|---|---|---|---|
| Infants | 0.0272 | 5 | 0.136 |
| Toddlers | 0.0272 | 12 | 0.326 |
| Other children | 0.0334 | 23 | 0.768 |
| Adolescents | 0.0150 | 52.4 | 0.786 |
| Adults | 0.0078 | 70 | 0.546 |
| Elderly | 0.0072 | 70 | 0.504 |
| Very elderly | 0.0077 | 70 | 0.539 |
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Taxonomy
TopicsAgricultural safety and regulations · Effects and risks of endocrine disrupting chemicals · Pesticide Residue Analysis and Safety
INTRODUCTION
1
Background and Terms of Reference
1.1
Regulation (EC) No 1831/20031 establishes the rules governing the Community authorisation of additives for use in animal nutrition. In particular, Article 14(1) of that Regulation lays down that an application for renewal shall be sent to the Commission at the latest 1 year before the expiry date of the authorisation.
The European Commission received a request from BASF SE, DSM Nutritional Products Ltd., represented in the EU by DSM Nutritional Products Sp.z.o.o., Europe‐Asia GmbH, JYB Europe BV, NHU Europe GmbH2 for the renewal of the authorisation of the additive consisting of beta‐carotene (3a160(a)) when used as a feed additive for all animal species (category: nutritional; functional group: vitamins, pro‐vitamins and chemically well‐defined substances having similar effect).
According to Article 7(1) of Regulation (EC) No 1831/2003, the Commission forwarded the application to the European Food Safety Authority (EFSA) as an application under Article (14)1 (renewal of the authorisation). The dossier was received on 31 July 2024 and the general information and supporting documentation are available at https://open.efsa.europa.eu/questions/EFSA‐Q‐2024‐00504. The particulars and documents in support of the application were considered valid by EFSA as of 12 September 2024.
According to Article 8 of Regulation (EC) No 1831/2003, EFSA, after verifying the particulars and documents submitted by the applicant, shall undertake an assessment in order to determine whether the feed additive complies with the conditions laid down in Article 5. EFSA shall deliver an opinion on the safety for the target animals, consumer, user and the environment and on the efficacy of the feed additive consisting of beta‐carotene, when used under the proposed conditions of use (see Section 3.1.3).
Additional information
1.2
Beta‐carotene is currently authorised for use in feed for all animal species (3a160(a)).3 The FEEDAP Panel issued an opinion on the safety and efficacy of this product when used in feed for all animal species (EFSA FEEDAP Panel, 2012).
DATA AND METHODOLOGIES
2
Data
2.1
The present assessment is based on data submitted by the applicant in the form of a technical dossier4 in support of the authorisation request for the use of beta‐carotene as a feed additive.
The confidential version of the technical dossier was subject to a target consultation of the interested Member States from 18 September 2024 to 18 December 2024; the comments received were considered for the assessment.
In accordance with Article 38 of the Regulation (EC) No 178/20025 and taking into account the protection of confidential information and of personal data in accordance with Articles 39 to 39e of the same Regulation, and of the Decision of EFSA's Executive Director laying down practical arrangements concerning transparency and confidentiality,6 a non‐confidential version of the dossier has been published on Open.EFSA.
According to Article 32c(2) of Regulation (EC) No 178/2002 and to the Decision of EFSA's Executive Director laying down the practical arrangements on pre‐submission phase and public consultations, EFSA carried out a public consultation on the non‐confidential version of the technical dossier from 12 March to 02 April 2025, for which no comments were received.
The FEEDAP Panel used the data provided by the applicant together with data from other sources, such as previous risk assessments by EFSA or other expert bodies, peer‐reviewed scientific papers, other scientific reports and experts' (elicitation) knowledge, to deliver the present output.
The European Union Reference Laboratory (EURL) considered that the conclusions and recommendations reached in the previous assessment regarding the methods used for the control of beta‐carotene in animal feed are valid and applicable for the current application.7
Methodologies
2.2
The approach followed by the FEEDAP Panel to assess the safety and efficacy of beta‐carotene is in line with the principles laid down in Regulation (EC) No 429/20088 and the relevant guidance documents: Guidance on the renewal of the authorisation of feed additives (EFSA FEEDAP Panel, 2021).
ASSESSMENT
3
The additive beta‐carotene is currently authorised as a nutritional additive (functional group: vitamins, pro‐vitamins and chemically well‐defined substances having similar effect) for use in feed for all animal species. This assessment regards the renewal of the authorisation of the additive beta‐carotene in the form of the active substance and its preparations.
Characterisation
3.1
Characterisation of the active substance
3.1.1
Beta‐carotene (IUPAC name 1,3,3‐trimethyl‐2‐[(1E,3E,5E,7E,9E,11E,13E,15E,17E)‐3,7,12,16‐tetramethyl‐18‐(2,6,6‐trimethylcyclohex‐1‐en‐1‐yl)octadeca‐1,3,5,7,9,11,13,15,17‐nonaen‐1‐yl]cyclohex‐1‐ene) is produced by chemical synthesis and it appears as crystalline powder with the Chemical Abstracts Service (CAS) number 7235‐40‐7, the EU number 230‐636‐6, a molecular formula C_40_H_56_ and a molecular weight of 536.88 g/mol.
The current authorisation states that beta‐carotene is produced in solid form, either by chemical synthesis or by fermentation with Blakeslea trispora Thaxter slant XCPA 07‐05‐1 (CGMCC 7.44) and XCPA 07‐05‐2 (CGMCC 7.45). It also sets a specification for the active substance of a minimum of 96% total colouring matters (dried substance) expressed as beta‐carotene, and carotenoids other than beta‐carotene ≤ 3% of total colouring matters.
In the present application, the applicants state that the manufacturing process by chemical synthesis has not significantly changed since the previous authorisation (Regulation (EU) 2015/1103). The applicants state that the manufacturing by fermentation is not supported anymore, and no data are provided in this application.9 The applicant submitted data on the batch‐to‐batch variation, impurities10 and physical properties11 of the additive, which are reported in Table 1.
The data provided by the applicants confirmed compliance with the specifications set by the authorisation Regulation (EU) No 2015/1103 and the levels of residual solvents are below the limits set by VICH (2023). The FEEDAP Panel considers that the amounts of the detected impurities do not raise safety concerns.
Characterisation of the preparations
3.1.2
According to the current authorisation, beta‐carotene may be placed on the market and used as an additive consisting of a preparation. Also, the additive is specified to contain less than 100 mg triphenylphosphine oxide (TPPO) per kg additive.12
The applicants provided examples of commercial preparations containing 10% beta‐carotene and listed examples of ingredients used as carriers (gelatine, carbohydrates, calcium lignosulfonate), anticaking agents (silicic acid, tricalcium phosphate) and antioxidants (BHT, sodium ascorbate, alpha‐tocopherol, tocopherol‐rich extract, vitamin C, ascorbyl palmitate). The applicants reported that, compared to the previous assessment, the antioxidant used in the preparation has been changed from ethoxyquin to the ones listed above.
The applicant submitted data on the batch‐to‐batch variation, impurities13 and physical properties14 of different preparations which are reported in Tables 2 and 3.
The data provided by the applicant showed compliance with the specifications set in the Regulation (EU) 2015/1103. The Panel notes that the levels of TPPO were not measured in one of the preparations (Company B), while Company D declared that ■■■■■. Company B provided data on the levels of TPPO in the active substance, which were below 45 mg/kg (Table 1). The FEEDAP Panel considers that the amounts of the detected impurities do not raise safety concerns.
Considering the minor changes in the manufacturing process with the replacement of the antioxidant, the applicants provided new data on the density, dusting potential, particle size distribution and stability which are reported in Table 3.
Conditions of use
3.1.3
The additive is currently authorised for use as a nutritional additive in feed for all animal species without a maximum or minimum level.
Under other provisions of the authorisation, it is specified that:
- Beta‐carotene may be placed on the market and used as an additive consisting of a preparation.
- In milk replacers for calves, it is recommended a maximum content of 50 mg of beta‐carotene/kg of milk replacer.
- In the directions for use of the additive and premixture, indicate storage and stability conditions.
- For safety: breathing protection shall be worn during handling.
The applicants did not request any changes in the current conditions of the authorisation.
Safety
3.2
In the previous assessment (EFSA FEEDAP Panel, 2012), the FEEDAP Panel concluded that the use of beta‐carotene is safe for the target animals, assuming that the triphenylphosphine oxide (TPPO) does not exceed 100 mg/kg additive. Regarding consumer exposure, the Panel concluded that it is prudent, in the absence of an acceptable daily intake (ADI), that supplemental beta‐carotene in animal feed should not significantly add to consumer exposure from other sources. Among food‐producing animals, the consumption of liver from veal calves may result in additional exposure, so unlimited use of beta‐carotene as an additive in milk replacers may be a concern for consumer safety. For user safety, the FEEDAP Panel concluded that the additive is not a skin and eye irritant nor a skin sensitiser, but respiratory exposure is considered potentially hazardous. The Panel found it unlikely that the use of beta‐carotene in animal nutrition poses a risk to the environment.
The applicants stated that no adverse effects have been notified concerning the safety of target animals, consumers, users and the environment during the years since the authorisation of the additive.15
Extensive literature search
3.2.1
The applicants conducted an extensive literature search (ELS)16 to support the safety of beta‐carotene for all target species, consumers, environment and users under the authorised conditions of use. The ELS covered the period from January 2013 (authorisation of the feed additive) until September 2023. For the ELS, 29 databases were used, including 4 cumulative, 13 single and 12 publisher databases.17 The search terms and the inclusion/exclusion criteria were provided. In addition to the automatic ELS, a complementary search using Google Scholar and two independent manual searches of relevant articles for the safety of beta‐carotene were conducted. These searches resulted in a total of 121 publications potentially relevant for the safety assessment.
The FEEDAP Panel assessed all of them and considered that no new information was provided that would lead to reconsider its previous conclusions on the safety for the target species and the environment. Some papers were considered relevant for the safety for the consumer and user and are reported below.
Safety for the target animals and the environment
3.2.2
Considering that the manufacturing process and the composition of the additive have not been modified since the previous authorisation and no relevant new information was found in the literature search, the Panel concludes that the additive beta‐carotene produced by chemical synthesis remains safe for the target species and the environment under the current conditions of the authorisation.
Safety for the consumer
3.2.3
From the literature search, 69 papers were retrieved and identified by the applicant as relevant for consumer safety. The FEEDAP Panel reviewed them and considered two papers as relevant for the assessment of consumer safety.
The FEEDAP Panel noted that a health‐based guidance value (e.g. tolerable upper intake level – UL, acceptable daily intake – ADI) has not been established for beta‐carotene. In the previous FEEDAP Panel assessment, the applicant provided a worst‐case scenario for consumer exposure based on literature data on beta‐carotene. The results of this calculation suggested that the contribution of beta‐carotene from food of animal origin to the total intake is low (0.368 mg/day) compared to the estimated intake of 3–7 mg/day (EFSA FEEDAP Panel, 2012).
Recently, the EFSA Nutrition, Novel Foods and Food Allergens (NDA) Panel issued an opinion on the tolerable upper intake level for preformed vitamin A and beta‐carotene and concluded that there is no indication that beta‐carotene intake from the background diet is associated with adverse health effects, and therefore, no UL or safe level of intake can be established. However, the NDA Panel highlighted that smokers should avoid consuming food supplements containing beta‐carotene due to an increased risk for lung cancer. In addition, the NDA Panel calculated the human exposure to beta‐carotene from natural sources (fruit and vegetables) and food additives and considered that the main food groups contributing to background beta‐carotene intake are vegetables and vegetable products (mainly carrots, tomatoes, spinach), and fruit/vegetable juices and nectars, in all population categories (EFSA NDA Panel, 2024).
In the current assessment, the FEEDAP Panel performed an updated consumer exposure assessment following the methodology described in the Guidance on consumer safety (EFSA FEEDAP Panel, 2017). Based on the literature search provided by the applicant, the Panel identified two relevant papers (Jin et al., 2015; Miao et al., 2023) reporting new residue data not available at the time of the previous assessment. The studies are described below.
One hundred and twenty cattle for fattening received supplementary beta‐carotene at concentrations of 0 (control), 600, 1200 or 1800 mg/day (corresponding to 66, 122 and 188 mg/kg complete feed, approximately) for 90 days (30 animals per group) and then received no supplementation for 60 days. At the end of the supplementation period (90 days), beta‐carotene deposition was evaluated in several organs and tissues and was found to be significantly increased in liver (2.52 vs. 7.43, 8.39 and 9.32 μg/g), muscle (0.18 vs. 0.19, 0.28, 0.33 μg/g) and subcutaneous fat (0.53 vs. 1.29, 1.86 and 2.54 μg/g) (Jin et al., 2015).
A total of 600 Hy‐line Brown laying hens at 40 weeks of age received supplementary beta‐carotene at concentrations of 0 (control), 15, 30, 60 and 120 mg/kg feed. After a 14‐week trial, samples were collected and the deposition of beta‐carotene in organs and tissues was investigated. Beta‐carotene deposition significantly increased in the liver (< limit of quantification (LOQ) vs. 1.67, 2.3, 7.97 and 16.9 μg/g), and in egg yolk (< LOQ vs. 1.42, 1.98, 4.72 and 10.3 μg/g) (Miao et al., 2023).
Beta‐carotene is currently authorised in all animal species without a maximum level (except for milk replacer 50 mg/kg feed). However, the applicant proposed some maximum recommended levels for beta‐carotene, as follows: 20 mg/kg feed for rabbits, 30 mg /kg feed for chickens for fattening, laying hens, turkeys for fattening, pigs for fattening, piglets, sheep/goat, salmon and ornamental fish, 50 mg/kg feed for veal calves, cattle for fattening, dairy cows, dogs and cats, 57 mg/kg feed in lactating sows and 100 mg/kg feed for horses.
Therefore, the FEEDAP Panel considered it appropriate to use deposition data obtained from supplementation levels closer to the condition of use of the additive in practical farming conditions for the consumer exposure assessment: 30 mg beta‐carotene/kg feed for laying hens in the study by Miao et al. (2023) and 600 mg beta‐carotene/day (corresponding to 66 mg beta‐carotene/kg feed for cattle for fattening) in the study by Jin et al. (2015). Deposition data in milk was not present, and therefore, the FEEDAP Panel used the same value as in the previous assessment (EFSA FEEDAP Panel, 2012).
The input data used are reported in Table 4.
No deposition data were available for all animals' tissues and products (no data were retrieved for the following food categories: ‘Birds’ fat tissue’, ‘Birds' meat’, ‘Birds' offals and slaughtering products (other than liver)’, ‘Fish’, ‘Honey’, ‘Mammals' offals and slaughtering products (other than liver)’ and ‘Seafood’). However, the FEEDAP Panel considered that liver is the main site of beta‐carotene deposition and accumulation in most animal species (EFSA FEEDAP Panel, 2012), for which deposition data are available.
The results of the dietary exposure to beta‐carotene for the different population categories are reported in Table 5.
The calculated consumer exposure to beta‐carotene ranged from 0.136 mg/day (infants) to 0.786 mg/day (adolescents). The FEEDAP Panel notes that these results are less than 10% of the exposure values calculated by the NDA Panel considering different sources of beta‐carotene (6.6 mg/day in female infants to 11 mg/day in female older adolescents ≥ 14 to < 18 years) (EFSA NDA Panel, 2024).
Based on the above, the FEEDAP Panel considers that the new studies identified in the literature search do not provide any additional information to the current assessment that would change the conclusions previously reached regarding consumer safety.
Conclusions on safety for the consumer
3.2.3.1
The FEEDAP Panel concluded that beta‐carotene remains safe for consumers at the authorised use levels.
Safety for the user
3.2.4
In its previous opinion (EFSA FEEDAP Panel, 2012), the FEEDAP Panel concluded, based on data from studies performed with beta‐carotene obtained by fermentation, that the active substance is not irritant to the skin or eyes and is not a skin sensitiser.
Based on the highest dusting potential measured value (Section 3.1.2), the FEEDAP Panel considers that the exposure of users through inhalation is likely.
In addition, the literature search retrieved five studies. One of these studies (Freitas & Gaspar, 2016) was considered relevant by the FEEDAP Panel and is described below.
Beta‐carotene phototoxicity was tested, isolated and combined with other substances (e.g. apigenin, chrysin, bemotrizinol), using the 3T3 NRU phototoxicity test. Phototoxic potential was observed for beta‐carotene, isolated and combined, after UVA/VIS exposure. Although positive results were observed, this in vitro test cannot be used as a stand alone to predict the exact incidence of phototoxic reactions in humans. Therefore, its relevance for the current assessment is limited.
The applicant provided studies on the skin and eye irritation and skin sensitisation of beta‐carotene (crystalline) and a study on skin sensitisation of a 10% preparation of beta‐carotene.
The skin irritation potential of beta‐carotene was tested in a study performed according to OECD Testing Guideline (TG) 404,18 which showed that beta‐carotene is not a skin irritant.
The eye irritation potential of the beta‐carotene was tested in a study performed according to OECD TG 492,19 which showed that the additive is a potential eye irritant; however, the test on its own is not sufficient to conclude on eye irritation. The eye irritation potential of the beta‐carotene was further tested in a study performed according to OECD TG 437,20 which showed that the additive is not an eye irritant.
The skin sensitisation potential of beta‐carotene was tested in a study performed in 198321 in guinea pigs and prior to standardisation of the test method. The study used groups of 10 animals but was otherwise similar to the standard maximisation test (OECD TG 406). The test showed that the additive is not a skin sensitiser.
The skin sensitisation potential of a 10% preparation containing 13.1% beta‐carotene was tested in a study performed according to OECD TG 429,22 which showed that the test item is not a skin sensitiser.
Conclusions on safety for the user
3.2.4.1
Based on the information available, beta‐carotene should not be considered a skin and eye irritant and not a skin sensitiser. One preparation containing 10% beta‐carotene was shown not to be a skin sensitiser. However, no conclusions on the safety for the user can be done on any other preparations.
Efficacy
3.3
The present application for renewal of the authorisation does not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive. Therefore, there is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.
Post‐market monitoring
3.4
The FEEDAP Panel considers that there is no need for specific requirements for a post‐market monitoring plan other than those established in the Feed Hygiene Regulation23 and good manufacturing practice.
CONCLUSIONS
4
The applicant provided evidence that the additives currently in the market comply with the conditions of the authorisation. The current assessment covers only beta‐carotene produced by chemical synthesis and not by fermentation.
The FEEDAP Panel concludes that the use of beta‐carotene in animal nutrition under the approved conditions remains safe for target species, consumers and the environment.
Regarding user safety, the FEEDAP Panel concludes that beta‐carotene is not a skin and eye irritant and not a skin sensitiser. One preparation containing 10% beta‐carotene was shown not to be a skin sensitiser. However, no conclusions on the safety for the user can be done on any other preparations.
There is no need to assess the efficacy of the additive in the context of the renewal of the authorisation.
ABBREVIATIONSADIacceptable daily intakeBWbody weightCASChemical Abstracts ServiceCFUcolony‐forming unitDMdry matterELSextensive literature searchFEEDAPEFSA Scientific Panel on Additives and Products or Substances used in Animal FeedHRPhighest reliable percentileIUPACInternational Union of Pure and Applied ChemistryLOQlimit of quantificationNDANovel Foods and Food AllergensOECDOrganisation for Economic Co‐operation and DevelopmentPCBspolychlorinated biphenylsPhEurEuropean PharmacopoeiaRHrelative humidityTEQtoxic equivalency factorsTGTesting GuidelineTPPOTriphenylphosphine oxideULUpper levelVICHVeterinary International Conference on HarmonizationWHOWorld Health Organization
REQUESTOR
European Commission
QUESTION NUMBER
EFSA‐Q‐2024‐00504
COPYRIGHT FOR NON‐EFSA CONTENT
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PANEL MEMBERS
Roberto Edoardo Villa, Giovanna Azimonti, Eleftherios Bonos, Henrik Christensen, Mojca Durjava, Birgit Dusemund, Ronette Gehring, Boet Glandorf, Maryline Kouba, Marta López‐Alonso, Francesca Marcon, Carlo Nebbia, Alena Pechová, Miguel Prieto‐Maradona, Ilen Röhe, and Katerina Theodoridou.
LEGAL NOTICE
Relevant information or parts of this scientific output have been blackened in accordance with the confidentiality requests formulated by the applicant pending a decision thereon by EFSA. The full output has been shared with the European Commission, EU Member States (if applicable) and the applicant. The blackening may be subject to review once the decision on the confidentiality requests is adopted by EFSA and in case it rejects some of the confidentiality requests.
The reference list from the paper itself. Each links out to its DOI / PubMed record.
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