Airborne endotoxin associated with industrial-scale production of protein products in gram-negative bacteria

Human and animal proteins of therapeutic value can be produced in E. coli, a gram-negative bacteria. Endotoxin, a cellular component, is reported to have clinically significant health effects. Operations--including culturing the microbe, separating solids by centrifugation, and mixing/homogenizing--had associated endotoxin levels ranging from 0.07 ng/m3 to 12.8 ng/m3. Utilizing a 10-fold safety factor under the threshold where clinically significant changes can be detected, an action level of 30 mg/m3 for large scale operations involving the use of E. coli was established. Operations conducted without engineering controls had maximum airborne endotoxin levels of 1812 ng/m3.