25 
Dr. Laird argued against prc^ibiting research cm tetanus and botulism toxins. 
He said it is highly important to develop vaccines for these toxins. 
Dr. Gottesman said that v^ile those toxins are placed in the prcAiibited 
category r the prohibiticm is not absolute, individuals may come to RAC 
with a case-by-case request for an exception to any prdiibiticm. 
Dr. Gottesman as)ced Dr. Gill v*iich route of delivery elicits the most 
sensitive enterotoxin respx^se. Dr. Gill replied that the enteral route 
was most effective. Tliese toxins are the only toxins v^ich are more toxic 
vAien administered entercdly than parenterally. Dr. Gottesman asked v^iere 
c^lera toxin would fall in the proposed classification on the basis of 
enteral and parenteral LD50S. Dr. Gill replied that cholera toxin would 
not be considered a toxin under the proposed classification when adminis- 
tered parenterally. The LD50 of cholera toxin administered enter ally, 
would place it under Section 2 -b of the proposed impend ix G, were there 
no Section 2 -c. 
Dr. Holmes praised the proposal presented by the working group but expressed 
several reservations. He said the premise that humans will be as sensitive 
eU5 the most sensitive of three small animal species is based cm data for 
seven toxins, as informat icm on human toxicity for most toxins is not 
available. This assunption may not be true for all toxins. He was also 
concerned with the question of creating new ecological niches. Staphy- 
lococcal enterotoxin F, iirplicated in toxic shock syndrome, is not highly 
toxic, yet we suddenly have the appearance of this new clinically important 
syndrome. He questioned vhether toxin producing recombinant organisms 
able to survive in other sites, such as vagina, respiratory tract, or 
wounds, might be highly hazardous. He felt additional data should be 
generated to address these questions. He suggested that a procedure 
involving case-by-case evaluaticxi, at least at some level, as with the 
specific proposal involving diphtheria toxin to be reviewed by the RAC 
later in the meeting, was expropriate until more information was gathered. 
Dr. Nightingale questioned the wisdom of discussing treatability in setting 
containment levels for the enterotoxins. Timing, availability of treatment, 
etc., eiffect the outcome of treatmait. Drs. McGarrity and Goldstein also 
<hjected to the concept that physical containment coiditions need not be 
as stringent if physiological remedies exist. Dr. Nightingale noted that 
toxins vhose end point is not inmediate death, such as those which cause 
cancer years later, are not included in the classification. 
Dr. Nightingale proposed that the classification of toxins be considered 
in context of the upcoming total review of the Guidelines. She moved to 
refer consideratic^ of the document to the working group for revision of 
the Guidelines. Dr. Goldstein seconded the moticm. 
Dr. Levine opposed the motion. He said that the classification generated 
by the ^ hoc working group cm toxins represented six months of work by 
expert toxicx>logists. The issue pxresented enormous challenges in reviewing 
available data, and in cxxistructing a proposal acx:eptable to all manbers 
of the woidcing grcxap. The proposed leuiguage is the working group's best 
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