Robin Sue Eichen Conn

Evaluation of protein safety in the context of agricultural biotechnology

One component of the safety assessment of agricultural products produced through biotechnology is evaluation of the safety of newly expressed proteins. The ILSI International Food Biotechnology Committee has developed a scientifically based two-tiered, weight-of-evidence strategy to assess the safety of novel proteins used in the context of agricultural biotechnology. Recommendations draw upon knowledge of the biological and chemical characteristics of proteins and testing methods for evaluating potential intrinsic hazards of chemicals. Tier I (potential hazard identification) includes an assessment of the biological function or mode of action and intended application of the protein, history of safe use, comparison of the amino acid sequence of the protein to other proteins, as well as the biochemical and physico-chemical properties of the proteins. Studies outlined in Tier II (hazard characterization) are conducted when the results from Tier I are not sufficient to allow a determination of safety (reasonable certainty of no harm) on a case-by-case basis. These studies may include acute and repeated dose toxicology studies and hypothesis-based testing. The application of these guidelines is presented using examples of transgenic proteins applied for agricultural input and output traits in genetically modified crops along with recommendations for future research considerations related to protein safety assessment.

Toxicity of Lactide in Dogs after 2 and 13 Weeks of Daily Oral Dosing

Two-week and 13-week studies were conducted to determine the toxicity of lactide when the compound is administered orally in gelatin capsules to beagle dogs. In the 2-week study, daily doses of 0, 10, 100, 400, 1000 and 2500 mg/kg body weight/day were administered to dogs of both sexes for 14 consecutive days. All dogs survived to the end of the study. Clinical signs consistent with irritation of the alimentary tract occurred in dogs in the 1000 and 2500 mg/kg dose groups. Reductions in body weight gain and in absolute and relative thymus weights were observed in the same two dose groups, and reductions in absolute and relative spleen weights were seen in the 2500 mg/kg dose group. These changes were considered to be secondary to the stress resulting from irritation of the gastrointestinal tract. Gross and microscopic lesions were indicative of irritation, and included dark foci and haemorrhage of the stomach lining, and erosion and ulceration of the stomach and the oesophagus. Also noted in all high-dose dogs was renal tubular regeneration, which may represent repair of previous necrosis of the tubular epithelium. In the 13-week study, no deaths occurred when dogs were given daily oral doses of 0, 4, 20 or 100 mg/kg body weight/day. No clinical signs of toxicity were observed, and the compound had no effect on body weights, food consumption, or any of the clinical chemistry, haematology or urinalysis parameters assessed. Gross and microscopic findings considered to be potentially related to lactide administration were minimal, and included a stomach focus in one dog of each sex in the 100 mg/kg group. The stomach focus in the 100 mg/kg female dog was manifested microscopically as a stomach ulcer. Based on these results, the primary toxic effect of lactide was considered to be irritation of the gastrointestinal tract, and the no-observed-adverse-effect level (NOAEL) after subchronic oral dosing in dogs was considered to be 100 mg/kg/day.