Assessment of the feed additive consisting of canthaxanthin (Carophyll® Red 10%) for breeder hens for the renewal of its authorisation (DSM Nutritional Products Ltd.)

TL;DR

This paper evaluates the safety and authorization renewal of a canthaxanthin feed additive for breeder hens, noting potential risks to humans and animals.

Contribution

The study provides a scientific assessment of canthaxanthin's safety and authorization renewal, including modifications to its formulation.

Findings

The additive is safe for target species and consumers under current conditions.

Current maximum residue limits may not be protective enough for combined exposure routes.

The additive is irritant and a skin sensitiser, posing a risk with any exposure.

Abstract

Following a request from the European Commission, the EFSA was asked to deliver a scientific opinion on the renewal of the feed additive consisting of canthaxanthin (Carophyll® Red 10%) for breeder hens and to modify the additive specifications by substituting ethoxyquin by 4.4% butylated hydroxytoluene (BHT) and increasing the limit for dichloromethane to 80 mg/kg. The additive complies with the conditions of the authorisation. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) notes that the proposed modifications for the additive are considered to be of no concern. The Panel concluded that CAROPHYLL®Red 10% remains safe for the target species and the consumer under the current authorised conditions of use for CAROPHYLL® Red 10%. The Panel noted that the current maximum residue limits (MRLs) set in the different authorisations for canthaxanthin may not be protective enough for the consumer when considering combined exposure by all possible routes. CAROPHYLL® Red 10% should be considered to be irritant to skin and eyes and the respiratory tract and to be a skin sensitiser; any exposure is considered a risk. In the absence of data, the Panel could not conclude whether the additive CAROPHYLL® Red 10% remains safe for the environment under the current conditions of the authorisation. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Tables

TABLE 1. Chronic dietary exposure (mg/kg body weight/day) to canthaxanthin calculated based on existing MRLs of 15 mg canthaxanthin/kg liver (wet tissue) and 2.5 mg canthaxanthin/kg skin/fat (wet tissue).

Population class	Maximum HRP a	% of the ADI b
Infants	0.0000	–
Toddlers	0.0033	11
Other children	0.0046	15
Adolescents	0.0009	3
Adults	0.0043	14
Elderly	0.0006	2
Very elderly	0.0022	7

TABLE 2. Chronic dietary exposure to canthaxanthin (mg/kg body weight/day) calculated based on existing MRLs in poultry and salmonids.

Population class	Maximum HRP a	% of the ADI b
Infants	0.033	110
Toddlers	0.065	217
Other children	0.061	204
Adolescents	0.036	120
Adults	0.029	98
Elderly	0.028	94
Very elderly	0.025	85

Full text

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 one year before the expiry date of the authorisation.

The European Commission received a request from DSM Nutritional Products Ltd.2 represented in the EU by DSM Nutritional Products Sp. z o.o.3 for the renewal of the authorisation of the additive consisting of canthaxanthin (CAROPHYLL^®^ Red 10%), when used as a feed additive for breeder hens (category: zootechnical additives; functional group: other zootechnical additives (stabilisation of reproductive performance)).

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 11 July 2023 and the general information and supporting documentation are available at https://open.efsa.europa.eu/questions/EFSA‐Q‐2023‐00485. The particulars and documents in support of the application were considered valid by EFSA as of 23 November 2023.

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 canthaxanthin (CAROPHYLL® Red 10%), when used under the proposed conditions of use (see Section 3.1.4).

Additional information

1.2

The additive is currently authorised in the EU as a feed additive for breeder hens (4d161g).4

EFSA has delivered several opinions on the safety and efficacy of canthaxanthin (EFSA FEEDAP Panel, 2013, 2014, 2025a, 2025b).

DATA AND METHODOLOGIES

2

Data

2.1

The present assessment is based on data submitted by the applicant in the form of a technical dossier5 in support of the authorisation request for the use canthaxanthin (CAROPHYLL® Red 10%) as a feed additive.

The confidential version of the technical dossier was subject to a target consultation of the interested Member States from 23 November 2023 to 23 February 2024; the comments received were considered for the assessment.

In accordance with Article 38 of the Regulation (EC) No 178/20026 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,7 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 7 March to 28 March 2024 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 the canthaxanthin in animal feed and tissues are valid and applicable for the current application.8

Methodologies

2.2

The approach followed by the FEEDAP Panel to assess the safety and the efficacy of CAROPHYLL® Red 10% is in line with the principles laid down in Regulation (EC) No 429/20089 and the relevant guidance documents: Guidance on the renewal of the authorisation of feed additives (EFSA FEEDAP Panel, 2021).

ASSESSMENT

3

The additive is currently authorised as a preparation containing 10% of canthaxanthin, produced by chemical synthesis, for use as a zootechnical additive (functional group: other zootechnical additives (stabilisation of reproductive performance)) in breeder hens. The applicant requested the renewal of its authorisation. The additive will be referred to in this opinion with its trade name Carophyll® Red 10%.

Characterisation

3.1

Characterisation of the active substance

3.1.1

Canthaxanthin (CTX, β‐carotene‐4,4‐dione, CAS number 514‐78‐3, EINECS N0 2208187 2) has the molecular formula of C_40_H_52_O_2_, and its molecular weight is 564.85 g/mol.

The canthaxanthin under evaluation is manufactured via a chemical synthesis. The applicant states that there have been no changes introduced in the manufacturing process since the original authorisation.

The authorising regulation sets a minimum purity for the active substance canthaxanthin of 96%. The analysis of five batches of canthaxanthin showed an average purity of 98.0% (97.2%–98.9%). The carotenoids other than canthaxanthin were also analysed and resulted in an average of 1.8% (1.6%–2.1%).

Five batches of canthaxanthin were analysed for the presence of cadmium, lead, mercury and arsenic; all of them were below the limit of quantification (LOQ) for the methods of analysis used.10

The applicant set specifications for dichloromethane, acetone and petroleum ether in the active substance (22,000 mg/kg dichloromethane, 3000 mg/kg acetone and 2000 mg/kg petroleum ether). ■■■■■11 ■■■■■.

Three batches of canthaxanthin were analysed for the content of triphenylphosphine oxide (TPPO). The content of TPPO in these three batches was below the limit of detection (LOD).12

Characterisation of the additive

3.1.2

The current authorisation specifies that the additive contains a minimum of 10% canthaxanthin, ≤ 2.2% ethoxyquin and ≤ 10 mg dichloromethane/kg additive. The applicant requested the modification of these specifications by substituting ethoxyquin by 4.4% butylated hydroxytoluene (BHT) and increasing the limit for dichloromethane to 80 mg/kg.

The applicant describes the formulation of the additive CAROPHYLL® Red 10% to contain 10% canthaxanthin, 4.4% BHT, 10% dextrin (yellow), 15% corn starch and 60.6% lignosulfonate.

Analytical data to confirm the specifications for the content of canthaxanthin were provided for five batches of the additive, showing the following average value: 10.6% (range: 10%–11%). The loss on drying of these batches was on average: 6% (range: 5%–7%).13

Dichloromethane was analysed in five batches and found below the LOQ except for one batch in which the concentration was 8 mg/kg.14 The FEEDAP Panel notes that this level is below the maximum levels set in the current authorisation (≤ 10 mg dichloromethane/kg additive) and well below both the new limit proposed (≤ 80 mg/kg) and the level of 600 mg/kg set in the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) GL18(R2) (VICH, 2023), and are therefore considered to be of no concern.

Five batches of the additive were analysed for the presence of cadmium, lead, mercury and arsenic; cadmium, mercury and arsenic were below the LOQ for the methods of analysis used; lead was 0.1 mg/kg in all five batches.15

The FEEDAP Panel considers that the amounts of the detected impurities do not raise safety concerns.

Physical properties of the additive

3.1.3

Considering the change in the composition of the additive (ethoxyquin replaced by BHT), the applicant provided new data on the physico‐chemical properties of the additive, including density, particle size, dusting potential, stability and homogeneity. These data were generated with CAROPHYLL® Red 10% containing canthaxanthin produced by fermentation with Yarrowia lypolitica. Considering the high purity of the canthaxanthin produced by fermentation (99%) and the substantial equivalence of the two additives, the Panel considers that these data are representative also for CAROPHYLL® Red 10% containing canthaxanthin produced by chemical synthesis. These data were already evaluated by the FEEDAP Panel in its recent opinion (EFSA FEEDAP Panel, 2025a) and are considered applicable to the current assessment.

Conditions of use

3.1.4

The additive CAROPHYLL® Red 10% is authorised for use in feed for breeder hens at a minimum and maximum content of 6 mg/kg complete feed.

The other provisions of the authorisation state:

1. In the directions for use of the additive and premixture, indicate the storage conditions and stability to heat processing.
2. The mixture of different sources of canthaxanthin shall not exceed 6 mg canthaxanthin/kg of complete feedingstuff.
3. The mixture of this preparation with canthaxanthin and other carotenoids is allowed provided that the total concentration of the mixture does not exceed 80 mg/kg of complete feedingstuff.
4. For user safety: breathing protection, safety glasses and gloves should be worn during handling.

The authorisation set the following maximum residue limits (MRL): 15 mg canthaxanthin/kg liver (wet tissue) and 2.5 mg canthaxanthin/kg skin/fat (wet tissue).

The applicant did not request any change in the current conditions of the authorisation.

Safety

3.2

The safety of CAROPHYLL® Red 10% for all poultry for breeding purposes was previously evaluated by the EFSA FEEDAP Panel (2013). In that opinion, the FEEDAP Panel concluded that synthetic canthaxanthin from CAROPHYLL® Red 10% is safe under the proposed conditions of use for the target species, consumer and environment. In the same opinion, based on the data submitted, it was concluded that canthaxanthin is not an irritant to skin or eyes and it is unlikely to be a skin sensitiser. In the absence of any information, CAROPHYLL® Red 10% was considered to be as an irritant to skin and eyes and a skin sensitiser. Exposure by inhalation of users, when handling CAROPHYLL® Red 10%, was expected to be minimal.

For the current assessment, the applicant provided (i) the outcome of a complaint reporting systems stating that no adverse effect notifications were received as concerns the safety for the target species, consumers, users/workers and the environment since the authorisation of the additive,16 (ii) submitted two literature searches covering different aspects of the safety of the additive and (iii) submitted additional information related to the safety of the additive for the user and the environment.

The applicant has proposed the substitution of ethoxyquin with BHT in the formulation of the additive CAROPHYLL® Red 10%. The FEEDAP Panel notes that BHT is at present authorised for all animal species and it is under re‐evaluation.

Literature search

3.2.1

The first literature search, covering the period 2014–2020, was already considered by the FEEDAP Panel in its opinion adopted in 2024 (EFSA FEEDAP Panel, 2025a).17 In that opinion, the FEEDAP Panel reviewed the relevant papers and concluded that none of them identified safety concerns of canthaxanthin for the target species or the consumer under the current conditions of authorisation.

For the second literature search,18 covering the years from 2020 to 2023, four cumulative databases (LIVIVO, NCBI, Ovid and Toxinfo), 13 single databases and 11 publisher databases were used. The keywords used covered different aspects of the safety, and the inclusion and exclusion criteria were provided. From a total of 144 retrieved publications, 12 publications were identified as relevant for the safety of the additive (8 for the safety of the target species and 4 for the safety for the consumer). None of the papers identified in the second literature search identified safety concerns of canthaxanthin for the target species, consumer, users and environment under the current conditions of authorisation.

Safety for the target species

3.2.2

In its previous opinion (EFSA FEEDAP Panel, 2013), the FEEDAP Panel concluded, based on a tolerance study in breeder hens, that canthaxanthin from CAROPHYLL® Red 10% is safe for breeder hens at the proposed concentration of 6 mg/kg complete feed with a safety margin of at least four.

Considering that the composition of the additive has not been substantially changed, with the exception of the substitution of ethoxyquin by BHT, and the increase in the specification of dichloromethane which is considered of no concern, and that no new studies were found in the literature that would change the previous conclusions on the safety of the canthaxanthin for the target species, the Panel concludes that the additive CAROPHYLL® Red 10% remains safe for the target species under the current approved conditions.

Safety for the consumer

3.2.3

Although eggs from breeding hens should normally not enter the food chain, the consumer might be exposed to residues of canthaxanthin from the consumption of food products derived from the hens or the accidental incorporation of their eggs in the food chain.

The toxicological profile of canthaxanthin was evaluated in previous EFSA opinions (EFSA ANS Panel, 2010; EFSA FEEDAP Panel, 2013, 2014). In these assessments, many aspects of toxicology including acute toxicity, repeat‐dose subchronic and chronic toxicity, carcinogenicity, genotoxicity, reproductive and developmental toxicity, immunotoxicology and special studies of effects on the eye were considered. A health‐based guidance value (acceptable daily intake—ADI) of 0.03 mg canthaxanthin/kg body weight was established by applying an uncertainty factor of 10 to a NOAEL (no observed adverse effect level) of 0.25 mg/kg body weight per day for scotopic b‐wave changes (without impairment of vision) in humans and a BMDL_05_ (benchmark dose (lower confidence limit)) of 0.2–0.33 mg/kg body weight per day for crystal incidence in a meta‐analysis of findings of crystals in the retina of humans exposed to canthaxanthin.

In 2013, the FEEDAP Panel concluded the following on the safety for the consumer: ‘The maximum proposed canthaxanthin concentration in feed for breeder hens does not exceed that already authorised for pigmenting eggs of the same animal category. Consequently, the intake of edible tissues and products from canthaxanthin‐treated poultry and salmonids does not exceed the ADI with respect to the established MRLs for poultry (and salmonid) tissues. Eggs produced for breeding purposes are not normally consumed. Even given the unlikely case that all eggs for breeding were consumed as table eggs, there would be no concern for consumer safety arising from the use of canthaxanthin from CAROPHYLL® Red 10% in breeding poultry at the dose of 6 mg/kg complete feed.’

Based on the above, the following maximum residue limits were established in the authorising regulation: 15 mg canthaxanthin/kg liver (wet tissue) and 2.5 mg canthaxanthin/kg skin/fat (wet tissue).

The literature search submitted by the applicant did not identify new studies that would change the previous conclusions on the safety of canthaxanthin for the consumer.

When assessing consumer exposure to canthaxanthin at the level of the existing MRLs using the methodology detailed in the guidance on consumer safety (EFSA FEEDAP Panel, 2017), the exposure of consumers is below the ADI in all the population classes (Table 1). For detailed results per age class, country and survey, see Appendix A, Table A.1.

Consumer exposure needs to take into consideration all potential dietary sources. Canthaxanthin is also authorised as a sensory additive (colourant) for use in chickens for fattening, minor poultry species for fattening, laying poultry and poultry reared for laying and the following MRLs are in force: 2.5 mg/kg skin/fat, 15 mg/kg liver, 30 mg/kg egg yolk (8.1 mg/kg whole egg containing 27% of yolk). MRLs for canthaxanthin (in combination with adonirubin19) are also set for a preparation of red carotenoid‐rich bacterium Paracoccus carotinifaciens as a feed additive for salmon and trout20 as follows: 10 mg/kg for the sum of adonirubin and canthaxanthin/kg muscle (wet tissue) for salmon and 8 mg/kg for the sum of adonirubin and canthaxanthin/kg muscle (wet tissue) for trout.

Consumer exposure considering the combined exposure from poultry and salmon was done using the above‐reported MRLs. The outcome of the calculation is shown in Table 2. For detailed results per age class, country and survey, see Appendix A, Table A.2.

When assessing consumer exposure to canthaxanthin at the level of the existing MRLs for poultry and trout/salmon, the exposure of consumers exceeds the ADI in the population classes infants, toddlers, other children and adolescents. The main contributors to the consumer exposure are eggs and fish.

Conclusions on the safety for the consumer

Based on the above, the FEEDAP Panel concludes that the use of canthaxanthin in feed for breeder hens under the current conditions of the authorisation remains safe for the consumers. However, the panel notes that the current MRLs set in the different authorisations for canthaxanthin may not be protective enough for the consumer when considering combined exposure by all possible routes.

Safety for the user

3.2.4

In 2013, the FEEDAP Panel concluded that canthaxanthin is not an irritant to skin or eyes and it is unlikely to be a skin sensitiser. In the absence of any information, CAROPHYLL® Red 10% was considered an irritant to skin and eyes and a skin sensitiser. Exposure by inhalation of users, when handling CAROPHYLL® Red 10%, was expected to be minimal.

Based on the highest dusting potential measured (1430 mg/m^3^), the FEEDAP Panel considers that the exposure of users through inhalation is likely.

No additional information on the safety of CAROPHYLL® Red 10% was submitted, other than the SDS for the additive, in which it is recognised that the additive may cause skin and eye irritation.21

Considering the above, the Panel concludes that CAROPHYLL® Red 10% should be considered to be irritant to skin and eyes and the respiratory tract and to be a skin sensitiser; any exposure is considered a risk.

Safety for the environment

3.2.5

In its previous opinion, the FEEDAP Panel concluded that the use of CAROPHYLL® Red 10% at the proposed maximum concentration in feed will not result in a substantial increase in the canthaxanthin concentration in the environment and consequently does not pose a risk to the environment (EFSA FEEDAP Panel, 2013). The FEEDAP Panel notes that these conclusions were based on an assessment performed in line with the FEEDAP guidance applicable at the time of the assessment (EFSA, 2008), and that an updated environmental risk assessment for canthaxanthin, performed in line with the current requirements of the FEEDAP guidance to evaluate the safety of the additive for the environment (EFSA FEEDAP Panel, 2019), would be required. The applicant did not provide an updated evaluation of the safety for the environment for canthaxanthin in line with the above‐mentioned guidance.22 Therefore, in the absence of such data, the FEEDAP Panel cannot conclude on whether the additive CAROPHYLL® Red 10% remains safe for the environment under the current conditions of the authorisation.

Efficacy

3.3

The present application for renewal of the authorisation does not include a proposal for amending or supplementing the conditions of the 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.

CONCLUSIONS

4

The additive complies with the conditions of the authorisation. The Panel notes that the proposed modifications for the additive are considered to be of no concern.

The Panel concluded that CAROPHYLL® Red 10% remains safe for the target species and the consumer under the current authorised conditions of use for CAROPHYLL® Red 10%.

The Panel notes that the current MRLs set in the different authorisations for canthaxanthin may not be protective enough for the consumer when considering combined exposure by all possible routes (poultry and salmonids).

CAROPHYLL® Red 10% should be considered an irritant to skin and eyes and the respiratory tract and to be a skin sensitiser; any exposure is considered a risk.

In the absence of data, the panel cannot conclude on whether the additive CAROPHYLL® Red 10% remains safe for the environment under the current conditions of the authorisation.

There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

RECOMMENDATIONS

5

The FEEDAP Panel recommends that:

• The provision ‘The mixture of different sources of canthaxanthin shall not exceed 6 mg canthaxanthin/kg of complete feedingstuff’ should be amended as follows: ‘The mixture of different sources of the active substance canthaxanthin shall not exceed 6 mg canthaxanthin/kg of complete feedingstuff.’
• The provision ‘The mixture of this preparation with canthaxanthin and other carotenoids is allowed provided that the total concentration of the mixture does not exceed 80 mg/kg of complete feedingstuff’ should be amended as follows: ‘The mixture of this additive with other additives containing canthaxanthin and other carotenoids is allowed provided that the total concentration of the mixture does not exceed 80 mg total carotenoids/kg of complete feedingstuff.’

The Panel notes that a revision of the MRLs for canthaxanthin when used in poultry and fish might be needed.

ABBREVIATIONSADIacceptable daily intakeANSEFSA Scientific Panel on Additives and Nutrient Sources added to FoodBWbody weightCASChemical Abstracts ServiceEURLEuropean Union Reference LaboratoryFEEDAPEFSA Scientific Panel on Additives and Products or Substances used in Animal FeedLODlimit of detectionLOQlimit of quantificationMRLmaximum residue limitNOAELno observed adverse effect level

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2023‐00485

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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

The scientific output published implements EFSA's decision on the confidentiality requests submitted on specific items. As certain items have been awarded confidential status by EFSA, they are consequently withheld from public disclosure by redaction.