Zinc oxide is an inorganic compound that has been used since the early 90s (Holm, 1993) as a treatment to reduce the incidence of weaning diarrhea. However, in 2015, the Committee for Veterinary Medicines (CVMP) detected an environmental risk arising from the use of zinc oxide and in 2017 the European Commission revoked the authorisations for the marketing of veterinary products containing zinc oxide, with a maximum period of 5 years. This decision has led to the search for alternatives capable of replacing zinc oxide.

About zinc oxide

Zinc oxide is the second most abundant heavy metal in the organism, only behind iron. It is an intracellular ion found mostly in the cell cytosol. Zinc has numerous cellular functions, as it intervenes in gene expression, stabilization of proteins structure, cellular breathing, stabilization of cell membranes and cytoskeleton, enzymes structure and function. In addition, it is part of some metalloenzymes with structural, regulatory and catalytic function. Therefore, it plays a fundamental role in animal metabolism.

Applications of zinc oxide

Zinc oxide is used as a preventive treatment for post-weaning diarrhea, applied in two ways:

• Additive: The use of zinc oxide as an additive is regulated by EU Regulation 1095/2016, which establishes a maximum of 150 ppm in feed.
• At therapeutic levels: As a therapeutic, it is used for 14 consecutive days at doses of 100 mg/kg body weight, which is equivalent to 2500 ppm in feed.

Post-weaning diarrhea is one of the pathologies that most commonly affect swine farms, characterized by intense to moderate watery diarrhea, decrease in weight gain and up to 25% mortality in the absence of treatment.

Pigs are weaned when they are 3 to 4 weeks of life. Early weaning is a moment of great stress for the piglet, for numerous causes that result in immune weakening, which causes an increase of the susceptibility to suffer from diarrhea. These causes include the absence of breast milk, which confers passive immunity, along with a poorly developed immune system, gastrointestinal disturbances associated with changes in diet, stress from mother separation and grouping with piglets of other sows..

Zinc oxide helps to maintain intestinal structure and function, decrease oxidative stress and reduce the prevalence of post-weaning diarrhea.

Hazards of zinc oxide

The main danger from the use of zinc oxide lies in its environmental accumulation. The use of manure from farms where animals are treated with veterinary medicinal products containing zinc oxide has been shown to result in a continued increase of zinc in ground, water and sediments. This environmental accumulation is especially concerning in acidic and sandy soils, which favor its transition to the aquatic environment. The problem is compounded by the non-volatile and non-degradable nature of the zinc oxide, so there are currently no effective environmental risk mitigation measures.

In addition to the environmental problem, the use of zinc oxide is associated with increased antimicrobial resistance due to co-resistance. There are studies that ensure that there is a correlation between high doses of zinc in diet and the increase of the prevalence of antibiotic-resistant bacteria.

Legislation on the use of zinc oxide

The use of zinc oxide as an additive was laid down in Regulation (EC) No 1831/2003. In 2005, an arbitration procedure conducted by the European Medicines Agency (EMEA) on the Gutal 1000 g/kg, a premix medicine for piglets, detected an environmental risk arising from the use of zinc oxide.

In February 2016, France and the Netherlands requested a conformity arbitration procedure to investigate the environmental risk and increased prevalence of antibiotic-resistant bacteria associated with the use of medicines with zinc oxide.

Following the study of the case, the Committee on Veterinary Medicines determined that the risk associated with the use of zinc oxide was greater than the benefits obtained and, therefore, recommended the refusal to grant marketing authorisations and the suspension of marketing authorisations in force for veterinary medicinal products containing zinc oxide for oral administration to food producing species.

Based on this recommendation, the European Commission, took the decision to revoke commercial authorisations or refuse the application for marketing authorisation for veterinary medicinal products with zinc oxide, within a maximum period of 5 years, through the Commission Execution Directive of 26/06/2017.

Alternatives to zinc oxide

In order to avoid productive losses associated with the prohibition of the use of zinc oxide, several preventive measures will be necessary. Such measures should include both changes in production management and changes in diet composition.

Measures in production management

It will be necessary to establish new vaccination protocols, which should be wider and more effective, to improve the biosecurity measures of the farm, including greater precautions in the entry and mixing of animals, greater control of environmental factors during wean and make, whenever possible, a later wean.

Feeding measures

Dietary changes will need to be implemented in order to avoid the appearance of post-weaning diarrhea after the elimination of zinc oxide. Among these changes that could be made, there is to supply of a greater amount of fiber to regulate the intestinal tract, decrease protein supply while ensuring an adequate amount of digestible aminoacids and limit the use of soybeans to 11 kg.

The inclusion of pronutrients in feed. These active molecules of plant origin have proven to be a viable alternative to the use of zinc oxide, as they help to maintain growth rates and even decrease the prevalence of diarrhea.

Pronutrients work by modulating gene expression, increasing the synthesis of functional proteins at the cellular level. They act in the digestive mucosa, improving digestion, nutrient absorption and the integrity of the digestive mucosa, especially at early ages.

In addition, these pronutrients do not have a pharmacological effect, because they stimulate physiology, so that they have no suppression period, leave no residues in animals or food and do not cause resistance.

Discussion

Zinc oxide has been used for a long time as a preventive treatment for post-weaning diarrhea in piglets. However, in the recent years, a problem has been identified arising from its environmental accumulation, which has led the European authorities to ban the marketing of products containing zinc oxide for animal production within 5 years. To avoid productive losses associated with post-weaning diarrhoea, changes in both production management and food as well as the inclusion of pronutrients in the diet will be necessary.

Bibliography

• Quiles, L. Hevia. (2017). Nutritional alternatives to zinc oxide in piglets. University of Murcia, Animal Production. Available in:https://www.produccionanimal.com/alternativas-nutricionales-al-rust-de-zinc-in-piglets/
• European Medicine Agency. (26/june/2017). Questions and answers on veterinary medicinal products containing zinc oxide to be administered orally to food producing species.
• Molist, R. Davin. (2013). Use of zinc oxide in piglets for the control of post-weaning diarrhoea. Argentine animal production site, pp. 1-4.
• Mendel (2017). Transition to zinc oxide-free diets. Available in: https://www.3tres3.com/articulos/transicion-a-dietas-sin-oxide-de-zinc_37932/
• European Union. Council Directive (EU) 2001/82 of 6 November 2001 establishing a Community code on veterinary medicinal products. Official Journal of the European Community L311, 28 November 2001, pp. 1-66.
• European Union. Decision (EU) 2017/4529, 26 June 2017 on marketing authorisations, under Article 35 of Directive 2001/82 EC of the European Parliament and of the Council, of veterinary medicinal products containing zinc oxide for their oral administration of species intended for food production. Official Journal of the European Union L311, 26 June 2017, pp. 1-4.