Safety evaluation of a novel muramidase for feed application

• Published in: Regulatory toxicology and pharmacology 2017-10, Vol.89, p.57-69
• Main Authors: Lichtenberg, J., Perez Calvo, E., Madsen, K., Østergaard Lund, T., Kramer Birkved, F., van Cauwenberghe, S., Mourier, M., Wulf-Andersen, L., Jansman, A.J.M., Lopez-Ulibarri, R.
• Format: Article
• Language: English
• Subjects: Acremonium - genetics; Animal Feed - toxicity; Animals; Chickens; Consumer Product Safety; Daphnia - drug effects; Eye - drug effects; Feed; Feed additive; Lysozyme; Muramidase; Muramidase - biosynthesis; Muramidase - genetics; Muramidase - toxicity; Rats; Safety; Skin - drug effects; Toxicity Tests, Acute; Toxicity Tests, Subchronic - methods; Toxicology; Trichoderma - enzymology; Trichoderma reesei
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2017.07.014

Safety evaluation of a muramidase produced by a Trichoderma reesei strain (safe lineage), expressing a muramidase gene isolated from Acremonium alcalophilum is presented. Intended use in feed of this enzyme is as digestive aid in broiler chickens. Muramidase 007, was non-mutagenic and non-clastogenic in vitro, and no adverse effects were observed in 90-day subchronic toxicity studies in rats at doses up to 1132 mg TOS/kg body weight/day. The enzyme did not exhibit, in vitro, skin, nor eye irritation potential. Acute aquatic toxicity evaluated on daphnia and algae showed absence of effect of the enzyme at the standard doses tested. Muramidase 007 was fully tolerated by broiler chickens in a 6-weeks tolerance study showing no adverse effects in any of the dietary treatments (0, 1×, 5× and 10× maximum recommended dose). In conclusion, Muramidase 007 is found to be toxicologically inert, and there are no worker's safety concerns if standard precautions are instituted and a non-dusty formulation is employed. Muramidase 007 is well tolerated by the target species (broiler chickens) and cause no harm to the environment. The beneficial safety evaluation of Muramidase 007 is in line with this type of enzyme that is found ubiquitously in nature. •A novel microbial muramidase is proposed and confirmed derived from a safe strain lineage.•The novel muramidase documented as low toxicological concern as feed enzyme.•Novel muramidase well tolerated in vivo in rats and chickens without adverse effects.•Safety margin of novel muramidase in chickens higher than 10× maximum recommended dose.