CDX-403

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

Halohydrin dehalogenase is an enzyme and after oral ingestion it will quickly be broken down by gastric juices, digestive enzymes and pancreatic proteolytic enzymes in the lumen of the gastrointestinal tract into peptides and amino acids. Enzymes and its breakdown products are found throughout the body and they are non-toxic. No enzymes are known that are acutely toxic. It is widely accepted that pure industrial enzyme proteins normally do not cause significant acute toxic effects (Collection of information on enzymes, European Commission, 2002). The main concerns arise from toxic by-products or contaminants of the fermentation process. This enzyme is produced by Escherichia coli BL21, an E.coli strain that is widely used for protein expression and that is fully sequenced. A potential endotoxin present is E.coli derived lipopolysaccharide, however it is unlikely that contamination with LPS will influence the acute toxicity of the enzyme as it will be present only in very limited amounts and more importantly it is found not to be highly toxic (Harper et al, Food and Chemical Toxicology 49 (2011)). No other endotoxins are produced by this strain which could contribute to its acute toxicity. Based on these considerations it is concluded that the acute oral toxicity of Halohydrin dehalogenase will be low and thus it is scientifically and ethically not justified to perform further animal testing to address this endpoint.