Safety of a feed additive consisting of Sepiolitic clay for all animal species (MYTA S.A.)

TL;DR

The paper concludes that sepiolitic clay is safe as a feed additive for all animal species at the recommended levels, though it poses some inhalation risks.

Contribution

The study confirms the safety of sepiolitic clay for all animal species at the maximum recommended level of 20,000 mg/kg feed.

Findings

Sepiolitic clay is safe for all animal species at 20,000 mg/kg feed.

It is a respiratory and dermal sensitiser and poses inhalation risks due to dusting and silica content.

No safety concerns for consumers or the environment were identified.

Abstract

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety of Sepiolitic clay as a technological feed additive for all animal species. In 2022, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) delivered an opinion on the safety and efficacy of the same additive. The Panel concluded that Sepiolitic clay used as a feed additive is safe for the consumers and the environment, and efficacious as a binder and anticaking agent in feed for all animal species under the proposed conditions of use. The additive was not considered an eye or skin irritant. However, it was considered a respiratory and dermal sensitiser. Due to the dusting potential and its silica content, the additive was considered a risk by inhalation. Regarding the target species, in the previous Opinion, the Panel concluded that the additive was safe for dairy ruminants and growing Suidae at the recommended use level (20,000 mg/kg feed), for chickens for fattening at 10,000 mg/kg feed and for salmonids at 17,600 mg/kg feed. No conclusion could be drawn for all other species/categories. Based on the tolerance studies in chickens for fattening and trout evaluated in the current assessment, and the ones in weaned piglets and dairy cows previously assessed, the Panel concluded that the inclusion of Sepiolitic clay at the maximum recommended level of 20,000 mg/kg complete feed is safe for all animal species.

Tables

TABLE 1. Description of the additive.

Category of additive	Technological additives
Functional group of additive	– Binders
	– Anticaking agents
Description	Sepiolitic clay
Target animal category	– Salmonids and chickens for fattening (modification of the conditions of the authorisation set out in Implementing Regulation (EU) 2023/263)
	– Animal species/categories other than dairy ruminants, weaned and fattening Suidae, salmonids and chickens for fattening (application for re‐evaluation under Article 10(2) of Regulation (EC) No 1831/2003
Applicant	MYTA S.A.
Type of request	– Opinion pursuant to Article 13(1) of Regulation (EC) No 1831/2003 as regards the use of the additive for salmonids and chickens for fattening
	– New opinion pursuant to Article 29(1)(a) of Regulation (EC) No 178/2002 as regards the use of the additive for animal species/categories other than dairy ruminants, weaned and fattening Suidae, salmonids and chickens for fattening

TABLE 2. Effects of the dietary supplementation of chickens for fattening with Sepiolitic clay on selected parameters.

	Control	1×	2×
Sepiolitic clay (mg/kg complete feed) *
Intended (starter/grower)	0	20,000	40,000
Calculated (starter/grower)	–	17,709/17,818	36,373/36,570
Mortality/culling (%)	3.8	4.4	3.4
Performance parameters
Final body weight (g)	2906	2900	2859
Average daily gain (g)	80.9	80.9	79.7
Average daily feed intake (g/bird)	107.3	107.5	106.9
Feed‐to‐gain ratio	1.33	1.33	1.34
Blood parameters
Heterophils (103/L)	2.03b	2.15ab	2.41a
Amylase (IU/L)	467a	409ab	332b
C‐reactive protein (ng/mL)	37.3b	48.7ab	55.8a
Organ weight (% body weight)
Thymus	0.284a	0.243ab	0.208b
Kidneys	0.550a	0.518ab	0.477b

TABLE 3. Effects of the dietary supplementation with Sepiolitic clay on selected parameters of trout.

	Control	1×	2×
Sepiolitic clay (mg/kg complete feed) *
Intended	0	20,000	40,000
Calculated	–	16,792	34,465
Mortality/culling (%)	0	0	0.6
Performance parameters
Final body weight (g)	125.9	124.0	125.2
Final standard length (cm)	21.4	21.2	21.2
Specific growth rate (% BW/day)	2.67	2.65	2.65
Feed intake (% BW/day)	1.49	1.49	1.50
Feed‐to‐gain ratio	0.82	0.83	0.83

Full text

INTRODUCTION

1

Background and Terms of Reference as provided by the requestor

1.1

Regulation (EC) No 1831/2003 establishes the rules governing the Union authorisation of additives for use in animal nutrition; in particular, Article 9 thereof defines the terms of the authorisation by the Commission.

The applicant, MYTA S.A., is seeking a Union authorisation of Sepiolitic clay for all animal species, as described in Table 1. In the EFSA (FEEDAP Panel) opinion of 4 May 2022 on the safety and efficacy of the additive consisting of Sepiolitic clay for all animal species, it was concluded that the additive is safe for dairy cows and for weaned piglets at the recommended use level (20,000 mg/kg feed). The conclusion was extrapolated to other dairy ruminants, pigs for fattening and other growing Suidae. The additive was considered safe for chickens for fattening at 10,000 mg/kg feed and for salmonids at 17,600 mg/kg feed. However, the Panel could not conclude on the safety of sepiolitic clay for other animal species/categories.

Based on that opinion, Sepiolitic clay was authorised as an additive belonging to the functional groups ‘binders’ and ‘anticaking agents’ for use for dairy ruminants, weaned and fattening Suidae, salmonids and chickens for fattening.

The Commission gave the possibility to the applicant to submit supplementary information and data to complete the assessment and to allow a revision of the EFSA's opinion with regard to the use of the additive for the animal species and categories other than dairy ruminants, weaned and fattening Suidae, salmonids and chickens for fattening.

The supplementary information and data have been transmitted by the applicant using the E‐Submission Food Chain Platform (application number FEED‐2023‐21114).

Those supplementary information and data also aim at demonstrating that the use of the additive for salmonids and chickens for fattening meets the conditions for authorisation set out by Regulation (EC) No 1831/2003 at a level of 20,000 mg per kg of complete feed, instead of 17,600 and 10,000 mg/kg feed, which are the maximum contents set out in Implementing Regulation (EU) 2023/263 for those species respectively.

In view of the above, and based on the supplementary information and data submitted by the applicant, the Commission requests EFSA to deliver:

• – a scientific opinion, in accordance with Article 13(1) of Regulation (EC) No 1831/2003, on whether a modification of the authorised conditions of use of the additive Sepiolitic clay for salmonids and chickens for fattening, consisting of a raising of the maximum content to a level of 20,000 mg per kg of complete feed, would still meet the conditions set out by Regulation (EC) No 1831/2003;
• – a new scientific opinion, in accordance with Article 29(1)(a) of Regulation (EC) No 178/2002, on the use of the additive Sepiolitic clay for animal species and categories other than dairy ruminants, weaned and fattening Suidae, salmonids and chickens for fattening, under the conditions of Regulation (EC) No 1831/2003.

Additional information

1.2

The additive is a preparation containing Sepiolitic clay. The additive is currently authorised for use in feed for dairy ruminants, weaned and fattening Suidae, chickens for fattening and salmonids (1g563).1

EFSA issued one opinion on the safety and efficacy of this product when used in feed for all animal species (EFSA FEEDAP Panel, 2022).

DATA AND METHODOLOGIES

2

Data

2.1

The present assessment is based on data submitted by the applicant in the form of supplementary information2 to a previous application on the same product.3 The dossier was received on 26/2/2024 and the general information and supporting documentation are available on Open.EFSA at https://open.efsa.europa.eu/questions/EFSA‐Q‐2024‐00117.

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 active substance in animal feed are valid and applicable for the current application.4

Methodologies

2.2

The approach followed by the FEEDAP Panel to assess the safety and the efficacy of Sepiolitic clay is in line with the principles laid down in Regulation (EC) No 429/20085 and the relevant guidance documents: Guidance on the identity, characterisation and conditions of use of feed additives (EFSA FEEDAP Panel, 2017a), Guidance on the assessment of the safety of feed additives for the target species (EFSA FEEDAP Panel, 2017b), Guidance on technical requirements for regulated food and feed product applications to establish the presence of small particles including nanoparticles (EFSA Scientific Committee, 2021).

ASSESSMENT

3

The additive under assessment, referred to as Sepiolitic clay, is a mixture of clay and non‐clay fractions containing a minimum of 40% of sepiolite (mineral) and 25% illite, and is intended to be used as a technological additive (functional groups: (g) binders and (i) anticaking agents) for all animal species at a maximum use level of 20,000 mg/kg complete feed.

In the previous assessment, the FEEDAP Panel concluded that the additive is safe for the consumers and the environment and that it was efficacious as a binder and anticaking agent in feed for all animal species under the proposed conditions of use (EFSA FEEDAP Panel, 2022). The additive was not considered an eye or skin irritant. However, it was considered a respiratory and dermal sensitiser. Due to the dusting potential and its silica content, the additive was considered a risk by inhalation.

The Panel concluded that the additive is safe for dairy ruminants and growing Suidae at the recommended use level (20,000 mg/kg feed), and for chickens for fattening at 10,000 mg/kg feed and for salmonids at 17,600 mg/kg feed. The Panel could not conclude on the safety of Sepiolitic clay for other animal species/categories. The applicant provided new data to address the gaps identified in the previous opinion, which are assessed below.

Characterisation of the additive

3.1

The FEEDAP Panel already assessed the characterisation of the product in terms of its mineralogical and chemical composition, manufacturing process and physicochemical properties (EFSA FEEDAP Panel, 2022). The applicant submitted additional particle size analysis data using scanning electron microscopy (SEM).6 Due to shortcomings identified in the methodology, the data did not allow to determine the particle size distribution of the fraction of small particles. In particular, the dispersion protocol was not in line with the methodology indicated in the Guidance on technical requirements for regulated food and feed product applications to establish the presence of small particles, including nanoparticles (EFSA Scientific Committee, 2021). Moreover, the image resolution was poor, which prevented to adequately assess the presence of small particles.

Safety for the target species

3.2

In the context of a previous application, the applicant provided four tolerance trials: one in chickens for fattening, one in weaned piglets, one in dairy cows and one in trout (EFSA FEEDAP Panel, 2022). Based on the tolerance trials submitted, the FEEDAP Panel concluded that Sepiolitic clay is safe for dairy cows and weaned piglets at 20,000 mg/kg feed, and the conclusion was extrapolated to other dairy ruminants, pigs for fattening and other growing porcine species. The additive was also considered safe for chickens for fattening at 10,000 mg/kg feed and for salmonids at 17,600 mg/kg feed. However, considering that it was not possible to establish a comparable margin of safety in the four major species, the Panel could not conclude on the safety of Sepiolitic clay for other animal species/categories.

In the current application, the applicant submitted two tolerance trials to support the safety for the target species: one in chickens for fattening and one in trout.

Safety for chickens for fattening

3.2.1

A total of 960 one‐day‐old male chickens for fattening (Ross 308) were distributed in 48 floor‐pens with 20 animals in each and randomly allocated to three experimental groups (16 replicates per group).7 Two basal diets (starter, from days 1 to 21; finisher, from days 22 to 35) based on ■■■■■ were either not supplemented (control) or supplemented with the additive to provide 20,000 (1× maximum use level) or 40,000 (2×) mg per kg complete feed. The content of the additive in the feed was confirmed based on the analysis of the mineral composition (content of SiO_2_, MgO and Al_2_O_3_). The experimental diets were offered ad libitum in pelleted form for 35 days. The finisher diet included an inert marker for the evaluation of the nutrient retention.

The health status and mortality were checked daily, and dead animals were weighed and necropsied. The birds were weighed at the start of the trial. Thereafter, the average pen body weight and the feed intake were recorded on days 21 and 35. The average daily feed intake, average daily gain and feed‐to‐gain ratio were calculated and corrected for mortality. From day 31 to 35, excreta samples were collected from each pen and pooled. Diet and excreta samples were analysed for dry matter, nitrogen, zinc, retinol, narasin and riboflavin. At day 35, two birds per pen were randomly selected, and the blood sampled and analysed for haematology8 and biochemistry.9 At the end of the experiment, two birds per pen were randomly selected, killed and the organ weights recorded and evaluated for gross pathology.

The productive performance, blood data and organ weights were analysed with a generalised linear model, considering the diet as fixed effect. The experimental unit was the pen for productive performance, and the individual animal for blood and organ traits. When differences between groups were observed, means were compared with Tukey test. For the proof of tolerance, the overdose group (2×) was tested on non‐inferiority compared to the reference groups (control and use level) comparing the body weight (non‐inferiority margin (Δ) = 71.5 g), average daily gain (Δ = 2.11 g), average daily feed intake (Δ = 3.37 g). The significance level was set at 0.05.

The main results of the study are shown in Table 2. The health of the animals was considered normal throughout the study. No significant differences were found in mortality (including culling) between groups. No significant differences between groups were observed in any of the zootechnical parameters. When the overdose group (2×) was compared with the control and the use level (1×) group, the non‐inferiority was demonstrated for all tested parameters.

Regarding the blood and organ evaluation, a dose‐dependent increase in the heterophils and C‐reactive protein and a reduction of the serum amylase activity and the relative weight of thymus and kidney were observed, which became significant at 2× compared to the control group. The Panel considered that the values observed in the amylase, heterophils and C‐reactive protein, were within reference ranges for healthy control broiler chicks and thus, these changes were not considered an adverse effect. Moreover, the values for C‐reactive protein are quite below the ones expected for an inflammatory response in birds. Regarding thymus and kidneys, no histopathological examination was performed. However, the Panel notes that the weights of thymus and kidneys were within the reference values for healthy animals and no macroscopic lesions and/or effects on blood‐related parameters were reported. Therefore, the absence of histopathological examination is not considered critical and the effects were not considered adverse. The availability of crude protein, retinol, zinc, riboflavin was not significantly affected by the dietary inclusion of the additive at 40,000 mg/kg in comparison with the control, and no interaction with narasin was observed. The retention of dry matter was decreased in the overdose group in comparison with control; however, this effect was not translated in lower growth.

Based on the results of the tolerance trial, in which no adverse effects were observed when Sepiolitic clay were supplemented at 40,000 mg/kg complete feed, the FEEDAP Panel concludes that the additive is safe in chickens for fattening at 20,000 mg/kg complete feed.

Safety for salmonids (trout)

3.2.2

A total of 540 female juveniles of Rainbow trout (Oncorhynchus mykiss L.; 3–5 months old; initial body weight = 10.5 g) were distributed in groups of 30 fish to 18 tanks, randomly allocated to three experimental groups (representing six replicate 500 L‐tanks per group).10 A basal diet, based on soy protein concentrate, wheat gluten meal, rapeseed oil and fish meal was either not supplemented (control) or supplemented with Sepiolitic clay at 20,000 (1×), and 40,000 (2×) mg/kg complete feed. The content of the additive in the feed was confirmed based on the analysis of the mineral composition (content of SiO_2_, MgO and Al_2_O_3_). The experimental feeds were provided in pelleted form at 3% fish body weight once daily for 93 days. The mortality and health status of fish were daily monitored; animals found dead were necropsied. On day 1, fish were individually weighed. Thereafter, ■■■■■, the individual fish weight and length and the tank feed intake were recorded. The specific growth rate, average daily feed intake, condition factor11 and feed‐to‐gain ratio were calculated for the whole experiment. At the end of the experiment (day 93), ■■■■■ fish per tank (■■■■■) were killed and visually inspected, blood sampled to determine haematological12 and biochemical13 parameters, and organs14 weighed and evaluated for gross pathology. The hepatosomatic index (■■■■■ and viscerosomatic index (■■■■■ were calculated. The experimental data were analysed ■■■■■ The significance level was set at 0.05.

Only one fish from the 2× group died. The inclusion of Sepiolitic clay supplementation of fish diets at all inclusion levels did not affect any of the performance and blood parameters recorded. Likewise, no abnormalities or injuries were identified in any of the fish evaluated for gross pathology and the histopathological evaluation of selected tissues revealed a normal organisation of organ samples (Table 3).

Based on the results of the tolerance trial, in which no adverse effects were observed when Sepiolitic clay were supplemented at 40,000 mg/kg complete feed, the FEEDAP Panel concludes that the additive is safe in Rainbow trout at 20,000 mg/kg complete feed.

Discussion of the safety studies for the target species

3.2.2.1

In the study in chickens for fattening assessed in the previous opinion, the supplementation of the experimental diets with Sepiolitic clay at 20,000 (1×) and 40,000 (2×) mg/kg complete feed resulted in higher feed intake and worse feed‐to‐gain ratio of the birds compared to the control group, and the relative weight of liver was higher in the 2× group compared to the control (no histopathology analysis was provided). The Panel considered these findings as adverse effects; therefore, the Panel concluded that 10,000 mg Sepiolitic clay/kg feed (0.5×) were safe for chickens for fattening (EFSA FEEDAP Panel, 2022).

In the trial in trout assessed in the previous opinion, the supplementation of the additive at 35,200 mg/kg feed (1.76×) resulted in lower final body weight, worse feed‐to‐gain ratio and higher visceral somatic index and liver score value of fish compared to those of the control group. The Panel considered these findings as adverse effects, so the Panel concluded that 17,600 mg Sepiolitic clay/kg feed (0.88×) were safe for trout (EFSA FEEDAP Panel, 2022).

The Panel considers that the absorption of clays is very limited, if any, and thus, the effects observed on performance would be linked to potential alterations of the absorption and digestibility of nutrients rather than related to systemic effects. The assessment of the safety for the target species is based on the concept that the higher the zootechnical performance of the animals in a given physiological stage, the more sensitive the endpoints would be to adverse situations. In the newly submitted studies, the performance of the chickens and trout was higher than the one observed in the studies assessed in the previous application. Moreover, both studies in chickens showed that the additive did not interfere with the availability of relevant nutrients (crude protein, retinol, riboflavin, zinc).

Considering the experimental design and the results of the tolerance trials submitted in the current and previous application, the FEEDAP Panel considers that the Sepiolitic clay is safe when included at 40,000 mg/kg in the feed of chickens for fattening and trout.

Conclusions on safety for the target species

3.2.2.2

The tolerance studies assessed in this and the previous opinion showed that the use of Sepiolitic clay in chickens for fattening, weaned piglets, dairy cows and trout up to the maximum proposed use level of 20,000 mg/kg complete feed is safe, with a margin of safety of at least 2. Considering that the safety of the additive has been demonstrated in four major target species with different metabolic capacities and with a similar margin of safety, the FEEDAP Panel concludes that the use of Sepiolitic clay at the maximum proposed use level of 20,000 mg/kg complete feed is safe for all animal species.

Post‐market monitoring

3.3

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 Regulation15 and Good Manufacturing Practice.

CONCLUSIONS

4

The use of Sepiolitic clay at 20,000 mg/kg complete feed is considered safe for all animal species.

ABBREVIATIONSBWbody weightDMdry matterEURLEuropean Union Reference LaboratoryFEEDAPEFSA Scientific Panel on Additives and Products or Substances used in Animal FeedIUinternational unitsSEMscanning electron microscopy

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2024‐00117

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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.