β-Agonists are used therapeutically in both human and veterinary medicine to widen narrowed airways (broncholysis) in asthmatic respiratory diseases, to inhibit labour (tocolysis) and to treat peripheral circulatory disorders. They are also known as β2-sympathomimetics or β2-adrenoceptor agonists. The use of β-agonists as fattening aids is prohibited in the European Union.

The β-agonists analysed belong to the chemical group of substituted phenylethanolamines.

If β-agonists are used, they can get into the organism and thus into animal foods.

According to Council Directive 96/22/EC, the use of β-agonists as fattening aids is prohibited in the European Union.

Regulation (EU) 37/2010 only sets maximum levels for clenbuterol for cattle and equidae. For all other β-agonists, no residues may be detectable in animal matrices.

Further information on the legal basis can be found under Information for healthcare professionals.

The illegal use of ß-agonists as growth promoters in animal fattening and compliance with the limit values for clenbuterol are monitored as part of the National Residue Control Plan (NRKP). Live animals and animals at slaughter are monitored to ensure traceability to the producer. As the NRCP serves the purpose of preventive consumer protection, sampling is risk-based, taking into account knowledge of regional or local conditions and investigating indications or suspicions of unauthorised animal treatments.

In the Department of Veterinary Medicinal Products, Hormones, Contaminants and Special Analysis of the Institute for Food Safety Vienna, around 250 samples are analysed for ß-agonists each year.

Matrices analysed:

• Liver
• urine
• blood
• Milk

Testing for residues and test methods

In the Department of Veterinary Drugs, Hormones, Contaminants and Special Analysis (THKS) at the Institute for Food Safety Vienna, we analyse food for residues of β-agonists as part of the NRKP. We are also the National Reference Laboratory for these substances.

According to the Commission Implementing Regulation (EU) 2021/808, a mass spectrometric method is required for the confirmation of banned substances.

Regular participation in international interlaboratory tests and in workshops of the responsible EU reference laboratory (EURL) in Berlin (Germany) ensure the quality of the results and the continuous further development of the analytical methods to the latest state of the art and research.

The range of analyses is constantly being expanded.

The effect as a broncholytic is based on the fact that β-agonists lead to a relaxation of the bronchial muscles by stimulating the β2-adrenoceptors. The only broncholytic that is commercially available as a veterinary medicinal product is clenbuterol.

Its effect as a tocolytic is based on the relaxation of the gravid uterus and thus the inhibition of labour, e.g. to prevent premature birth. The most common tocolytic is clenbuterol.

In high doses, some β-agonists have an influence on the protein-fat ratio, in favour of the protein content. The increased protein synthesis in the muscle cells leads to an increase in muscle mass and thus makes β-agonists interesting for use as growth promoters in animal fattening, which is prohibited in Europe, or as doping agents in humans. Clenbuterol in particular, probably the best-known and most effective representative of this group of substances, has been and continues to be used illegally. However, the illegal use of other β-agonists is also known.

The typical side effects of β-agonists include tachycardia (rapid heartbeat), arrhythmia (cardiac arrhythmia), tremor (trembling), hyperglycaemia (increase in blood sugar levels) and hypokalaemia (decrease in blood potassium levels). In the event of an overdose, all side effects are intensified and life-threatening tachyarrhythmias can occur.

Legal regulation

The use of β-agonists as fattening aids is prohibited in the European Union in accordance with Council Directive 96/22/EC. In Annex 1 of Delegated Regulation (EU) 2022/1644, β-agonists are listed under Group A (Pharmacologically active substances prohibited or not authorised for food-producing animals) as subgroup A1e.

Directive 96/22/EC was last amended by Directive 2008/97/EC of the European Parliament and of the Council of 19 November 2008, whereby the ban on β-agonists in animal production remained unaffected. Directive 2008/97/EC was transposed into Austrian law by the Hormone Regulation 2009(Federal Law Gazette II No. 218/2009).

Regulation (EU) 37/2010 only sets maximum levels for clenbuterol for cattle and equidae. For all other β-agonists, no residues may be detectable in animal matrices.

Further legal documents:

Ordinance of the Federal Minister of Health concerning the prohibition of the placing on the market of medicinal products containing certain substances with hormonal or thyrostatic effects or ß-agonists (Federal Law Gazette II No.229/2009).

Control of residues

In the Department of Veterinary Drugs, Hormones, Contaminants and Special Analysis(THKS) of the Institute for Food Safety Vienna, we analyse food for residues of β-agonists as part of the NRKP. We are also the National Reference Laboratory for these substances.

Analyses and range of tests

The analysed β-agonists belong to the chemical group of substituted phenylethanolamines. The range of analysed substances is constantly being expanded. The matrices analysed are liver, urine, blood plasma and milk.

The analytical method used is high-pressure liquid chromatography coupled with tandem mass spectrometry(LC-MSMS).