Safety and efficacy of Advastat® (containing 10 % acarbose produced by Actinoplanes utahensis CBS 961.70) as feed additive for cattle for fattening and dairy cows

Following a request from the European Commission, the European Food Safety Authority (EFSA) was asked to deliver a scientific opinion on the safety and efficacy of Advastat® (containing acarbose as active substance) as feed additive for cattle for fattening and dairy cows, under the category zootechnical and functional group digestibility enhancer. The applicant claims two benefits from using Advastat®: an effect on animal welfare (reduction of the risk of acidosis) and on animal performance (more favourable ruminal fermentation). Acarbose is already used in human medicine as an oral first-line or adjunctive treatment for reducing postprandial hyperglycaemia in Type II diabetes mellitus. Advastat® contains 10 % acarbose, a tetrasaccharide analogue produced by fermentation with Actinoplanes utahensis, which inhibits the activity of gastrointestinal amylases and glucosidases. Advastat® is intended to be used in feed of ruminating beef and dairy cattle to maintain optimal rumen pH (>5.5) by slowing down starch fermentation in the rumen. The maximum dose proposed by the applicant for Advastat® use is that equivalent to 1.2 mg acarbose kg-1 body weight (bw), corresponding approximately to 70 mg kg-1 and 35 mg acarbose kg-1 complete feedingstuffs (dry matter) for cattle for fattening and dairy cows, respectively. In vitro studies (six) used to evaluate the effects of acarbose either on rumen fluid or ruminal metabolism, indicated that acarbose dose-dependently reduces rumen fermentation and contributes to stabilising ruminal pH. In vivo trials included fistulated beef cattle fed acidotic rations and non-fistulated dairy cattle receiving high starch diets. Five short-term studies (two to six days) showed that acarbose reduced the risk of acidosis, as characterised by ruminal pH or lactate concentration. Four trials were conducted on dairy cows, with a cross-over design with three-week periods. The animals were fed a diet expected to induce sub-optimal rumen pH with or without acarbose. Although those studies showed that acarbose increased milk fat and yield but also decreased protein percentage, they were considered of too short duration. Upon EFSA’s request, three additional trials (84-87 days duration) were performed at in commercially operating dairy farms in the EU in order to study the effects of acarbose in early lactation ration using high amounts of fermentable carbohydrates on milk yield. Acarbose-treate animals showed positive or negative changes, sometimes significant, in milk production and composition compared to control animals. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) cannot conclude on the efficacy of Advastat® for cattle for fattening and dairy cows because benefits in healthy animals, under common farming practices in the EU, could not be demonstrated. However, the former conclusion does not exclude that acarbose might be efficacious in cases where cattle for fattening and dairy cows are at a specific risk or suffering of acidosis due to the particular feeding regime. A tolerance study, which aimed at evaluating the safety of acarbose in lactating cows when added in feed at 0, 35 and 350 mg acarbose kg-1 complete feed DM, was provided; this study did not provide evidence of toxicity with a 10-fold acarbose overdose. The FEEDAP Panel concludes that acarbose is safe at the level of 35 mg kg feed-1 DM in dairy cows. The FEEDAP Panel also considers likely that the conclusion for dairy cows is valid for cattle for fattening. Orally administered labeled acarbose is metabolised extensively in the digestive tract before absorption to a limited extent. No unchanged acarbose or C2 (both pharmacologically active) are found in excreta, milk and edible tissues from cattle administered acarbose. From the different toxicity studies provided, it can be concluded that acarbose is not genotoxic and most effects observed, even at the lowest dose tested (decrease in body weight, 45 mg kg-1 bw), can be related to its pharmacological activity. No NOEL, and consequently no ADI, could be derived from the data provided. However, the consumer will not be exposed to pharmacologically active acarbose or its metabolite (C2) following consumption of food from treated animals. Consequently, the FEEDAP Panel concludes that no safety concerns for the consumer would result from the use of acarbose at the proposed level in beef and dairy cattle. No marker residue could be identified, nor is it considered necessary. In the absence of data on eye and dermal irritation potential, and on skin/respiratory sensitisation, the default approach is to consider the compound as a potential irritant and sensitiser. In the absence of information on potential effects of metabolites on the environment, the FEEDAP Panel cannot fully assess the risk for the environment arising from the use of Advastat® in feedingstuffs for cattle. The FEEDAP Panel made some recommendations for modifications to the Register entry proposed by the applicant.