Attachment I, Page 7 
facilities and for validation of the integrity of physical containment must be 
developed at the outset as an integral component of facilities design. 
A second defense against colonization or infection of biotechnology workers is 
provided by "biological containment". Such containment will be achieved 
through the continuing use of debilitated microorganisms. Any tendency toward 
reduction in levels of "biological containment" through the introduction to 
industry of more robust, less highly debilitated organisms must be approached 
with great caution and will require careful reassessment of potential health 
risks. 
PRODUCT HAZARDS 
Exposure to the biologically active products and by-products of microorganisms 
containing rDHA constitutes a serious class of potential hazard in the 
biotechnology Industries. Because of the reactive nature of such products, 
exposure to eveh minute quantities may cause physiological ly significant 
effects. Occupational exposures to products in other sectors of the 
biotechnology and pharmaceutical industries have produced a spectrum of 
illnesses, including gynecomastia (in the packaging of estrogens) , 
Cushing's syndrome (in glucocorticoid manufacture),^^ nasal polyps (in 
production of menthol cough drops), recurrent epistaxis (in compounding of 
ferrous sulfate), and toxic hepatitis (following exposure to isopropanol plus 
carton tetrachloride) . The hazards of product exposure will extend 
throughout the full manufacturing process from initial production to final 
( 385 ) 
