'*4478 Federal Register 
deinonstrate that the fraction of the viral 
genome being utilized does not lead to 
productive infection. A U.S. Department 
of Agriculture permit is required for 
work with Class 5 agents (see Section 
V-R and V-T). 
Section ni-C-4-b. For experiments 
involving recombinant DNA, or DNA or 
RNA derived therefrom, involving 
whole animals, including transgenic 
animals, and not covered by Sections 
iil-C -1 or Ill-C-^-a, the appropriate 
containment shall be determined by the 
Institutional Biosafety Committee. 
Section IU-C-5. Experiments Involving 
Whole Plants 
Experiments to genetically engineer 
plants by recombinant DNA methods, to 
use such plants for other experimental 
purposes (e.g., response to stress), to 
propagate such plants, or to use plants 
together with microorganisms or insects 
containing recombinant DNA, may be 
conducted under the containment 
conditions described in Sections III-C- 
5-a through III-C-5-e. If experiments 
involving whole plants are not 
described in Section III-C-5 and do not 
fall under Sections IIl-A, Ill-B, or III- 
F.. they are included in Section III-D. 
Note. For recombinant DNA experiments 
billing under Sections llI-C-5-e through 111- 
C-5-d. physical containment requirements 
may he reduced to the next lower level by 
appropriate biological containment practices, 
such as conducting experiments on a virus 
with an obligate insect vector in the absence 
of that vector or using a genetically 
attenuated strain. 
Section III-C-5-a. BL3-P (Plants) or 
BL2-P + biological containment is 
recommended for experiments 
involving most exotic (see Section V-W) 
infectious agents with recognized 
potential for serious detrimental impact 
on managed or natural ecosystems when 
recombinant DNA techniques are 
associated with whole plants. 
Section Hl-C-S-b. BL3-P or BL 2 -P + 
biological containment is recommended 
for experiments Involving plants 
containing cloned genomes af readily 
transmissible exotic (see Section V'-W) 
infectious agents with recognized 
potential for serious detrimental effects 
on managed or natural ecosystems in 
which there exists the possibility of 
reconstituting the complete and 
functional genome of the infectious 
agent by genomic complementation in 
planta. 
Section IIl-C-5-c. BL4-P 
containmerrt is recommended for 
experiments with a small number of 
readily transmissible exotic (see Section 
V-W) infectious agents, such as the 
soybean rust fungus [Phakofipora 
pnehyrhizi) and maize streak or other 
/ Vol. 59, No. 127 / Tuesday, July 5. 1994 / Notices 
viruses in the presence,of their specific 
arthropod vectors, that htve the 
potential of being serious pathogens of 
major U.S. crops. 
Section IIl-C-5-d. BL3-P 
containment is recommended for 
experiments involving sequences 
encoding potent vertebrate toxins 
introduced into plants or associated 
organisms. Recombinant DNA 
containing genes for the biosynthesis of 
toxin molecules lethal for vertebrates at 
an LD 50 of <100 nanograms per kilogram 
body w^eight fall under Section IlI-B -1 
and require NIH/ORDA and 
Institutional Biosafety Committee 
approval before initiation. 
Section lIl-C-5-e. BL3-P or BL 2 -P + 
biological containment is recommended 
for experiments with microbial 
pathogens of insects or small animals 
associated with plants if the 
recombinant DNA-modified organism 
has a recognized potential for serious 
detrimental impact on managed or 
natural ecosystems. 
Section III-C- 6 . Experiments Involving 
More than 10 Liters of Culture 
The appropriate containment will be 
decided by the Institutional Biosafety 
Committee. Where appropriate. 
Appendix K, Physical Containment for 
Large Scale Uses of Organisms 
Containing Recombinant DNA 
Molecules, shall be used. Appendix K 
describes containment conditions Good 
Large Scale Practice through BL3-Large 
Scale. 
Section IlI-C-7. Human Gene Transfer 
Experiments Not Covered by Sections 
III-A-2, m-B-2. in-B-3, and Not 
Considered Exempt Under Section V-U 
Certain experiments involving the 
transfer of recombinant DNA or DNA or 
RNA derived from recombinant DNA 
into one or more human subjects that 
are not covered by Sections III-A-2, III- 
B- 2 , TII-B-3, and that are not 
considered exempt under Section V-U 
must be registered with NIH/ORDA. The 
relevant Institutional Biosafety 
Committee and Institutional Review 
Board must review and approve all 
experiments in this category prior to 
their initiation. 
Section III-D. Experiments That Require 
Institutional Biosafety Committee 
Notice Simultaneous With Initiation 
Experiments not included in Sections 
Ill-A. III-B. III-C, m-E, and their 
subsections are considered in Section 
III-D. All such experiments may be 
conducted at BLl containment. For 
experiments in this category, a 
registration document (see Section III- 
C) ffhall "be -dated and signed by the 
investigator and Filed with the local 
Institutional Biosafety Committee at the 
time the experiment is initiated. The 
Institutional Biosafety Committee 
reviews and approves all such 
proposals, but Institutional Biosafety 
Committee review and approval prior to 
initiation of the experiment is not 
required (see Section IV-A). For 
example, experiments in which all 
components derived from non- 
pathogenic prokaryotes and non- 
pathogenic lower eukaryotes fall under 
Section III-D and may be conducted at 
BLl containment. 
Section IIl-D- 1 . Experiments Involving 
the Formation of Recombinant DNA 
Molecules Containing No More Than 
Two-Thirds of the G^ome of Any 
Eukaryotic Virus 
Recombinant DNA molecules 
containiiig no more than two-thirds of 
the genome of any eukaryotic virus (all 
viruses from a single Family (see 
Section V-Q) being considered identical 
(see Section V-S)) may be propagated 
and maintained in cells in tissue culture 
using BLl containment. For such 
experiments, it must be demonstrated 
that the cells lack helper virus for the 
specific Families of defective viruses 
being used. If helper virus is present, 
procedures specified under Section III- 
C-3 should be used. The DNA may 
contain fragments of the genome of 
viruses from more than one Family but 
each fragment shall be less than two- 
thirds of a genome. 
Section III-D- 2 . Experiments Involving 
Whole Plants 
This section covers experiments 
involving recombinant DNA-modiFied 
whole plants, and/or experiments 
involving recombinant DNA-modiFied 
organisms associated wdth whole plants, 
except those that fall under Section ni- 
A, m-B, m-C, or III-E. It should be 
emphasized that knowledge of the 
organisms and judgment based on 
accepted scientific practices should be 
used in all cases in selecting the 
appropriate level of containment. For 
example, if the genetic modification has 
the objective of increasing pathogenicity 
or converting a non-pathogenic 
organism into a pathogen, then a higher 
level of containment may be appropriate 
depending on the organism, its mode of 
dissemination, and its target organisms. 
By contrast, a lower level of 
contamment may be appropriate for 
small animals associated with many 
types of recombinant DNA-modified 
plants. 
Section m-D-2-a. BLl— P is 
recommended for all experiments w'ith 
recombinant DNA-containing plants and 
Recombinant DNA Research, Volume 19 
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