Federal Register / Vol. 47, No. 102 / Wednesday. May 26, 1982 / Notices 
23115 
Forbidden Entry Into the United States 
by USD A Policy. ” 
“Appendix B-III-C. Organisms Which 
May Not Be Studied in the United States 
Except at Specified Facilities. " 
8. Appendix C. Exemptions Under lU- 
D-5. 
a. The language dealing with the 
introduction of genes coding for the 
biosynthesis of toxins in this Appendix 
would be modified to read: 
"Experiments involving the deliberate 
introduction of genes coding for the 
biosynthesis of molecules toxic for 
vertebrates." 
b. The abbreviation "CDC” would be 
deleted from this Appendix. 
9. Appendix F. Containment 
Conditions for Cloning of Genes Coding 
for the Biosynthesis of Toxins for 
Vertebrates. 
a. The title of Appendix F would be 
changed to read as follows: 
“CONTAINTMENT CONDITIONS 
FOR CLONING GENES CODING FOR 
THE BIOSYNTHESIS OF MOLECULES 
TOXIC FOR VERTEBRATES.” 
b. Section Appendix F-1, General 
Information, would read as follows: 
Appendix F-I. General Information. 
Appendix F specifies the containment to 
be used for the deliberate cloning of 
genes coding for the biosynthesis of 
molecules toxic for vertebrates. Cloning 
of genes coding for molecules toxic for 
vertebrates that have an LDso of less 
than 100 nanograms per kilogram body 
weight (e.g., microbial toxins such as the 
botulinum toxins, tetanus toxin, 
diphtheria toxin, Shigella dysenteriae 
neurotoxin) is prohibited. No specific 
restrictions shall apply to the cloning of 
genes if the protein specified by the gene 
has an LDso of 100 micrograms or more 
per kilogram of body weight. 
Experiments involving genes coding for 
toxic molecules with an LDso of 100 
micrograms or less per kilogram body 
weight shall be registered with ORDA 
prior to initiating the experiments. A list 
of toxic molecules classified as to LDso 
is available from ORDA. Testing 
procedures for determining toxicity of 
toxic molecules not on the list are 
available from ORDA. The results of 
such tests shall be forwarded to ORDA, 
which will consult with an ad hoc 
working group on toxic molecules prior 
to inclusion of the molecule on the list. 
(See Section IV-C-l-b-(2)-(e).)” 
c. The title of Section Appendix F-II 
would read: 
“Appendix F-II. Containment 
Conditions for Cloning Toxic Molecule 
Genes in E. coli K-12. ” 
d. In Section Appendix F-II, the work 
“toxins” would be replaced by the 
words “molecules toxic.” 
e. The title of Section Appendix F-III 
would read: 
"Containment Conditions for Cloning 
of Toxic Molecule Genes in Organisms 
Other Than E. coli K-12. ’’ 
f. Appendix F-III, Containment 
Conditions for Cloning of Toxic Genes 
in Organisms Other Than E. coli K-12 
would read: 
“Requests involving the cloning of 
genes coding for molecules toxic for 
vertebrates in host-vector systems other 
than E. coli K-12 will be evaluated by 
ORDA, which will consult with the ad 
hoc working group on toxic molecules. 
(See Section IV-C-l-b-(3}-(f).)” 
10. Appendix G. Physical 
Containment. 
a. A third paragraph would be added 
to new Section Appendix G-I as follows: 
“The 'Laboratory Safety Monograph, ’ 
available from ORJDA, describes 
practices, equipment, and facilities in 
detail.” 
11. Table of Contents. 
The table of contents would be 
rearranged to reflect the reorganization 
of the document and be expanded to 
better identify the position of various 
sections in the document. 
12. Appendices. 
All Appendices would be renumbered 
to reflect their status as Appendices. 
C. Proposed Revised Guidelines for 
Research Involving Recombinant DNA 
Molecules. 
Table of Contents 
I. Scope of the Guidelines 
I-A — Purpose 
I-B — ^Definition of Recombinant DNA 
Molecules 
I-C — General Applicability 
I-D— General Definitions 
II. Containment 
III. Containment Guidelines for Covered 
Experiments 
III-A — ^Experiments that Require RAC 
Review and NIH and IBC Approval 
Before Initiation 
III-B — Experiments that Require IBC 
Approval Before Initiation 
111-^1 — Experiments Using Human or 
Animal Pathogens (Class 2, Class 3, 
Class 4, or Class 5 Agents) as Host- 
Vector Systems 
III-B-2 — Experiments in which DNA from 
Human or Animal Pathogens. (Class 2, 
Class 3, Class 4, or Class 5 Agents) is 
Cloned in Nonpathogenic Prokaryotic or 
Lower Eukaryotic Host-Vector Systems 
III-B-3 — Experiments Involving the Use of 
Infectious Animal or Plant Viruses or 
Defective Animal or Plant Viruses in the 
Presence of Helper Virus in Tissue 
Culture Systems 
lII-B-4 — Recombinant DNA Experiments 
Involving Whole Animals or Plants 
III-^S — Experiments Involving More than 
10 Liters of Culture 
Ill-C — Experiments that Require IBC 
Notice Simultaneously with Initiation of 
Experiments 
III- D — Exempt Experiments 
IV. Roles ancLResponsibihties 
IV- A — Policy 
IV-B — Responsibility of the Institution 
rV-B-1 — General Information 
lV-B-2 — Membership and Procedures of 
the IBC 
IV-B-3 — Functions of the IBC 
IV-B-4 — Biological Safety Officer 
lV-B-5 — Prinicpal Investigator 
IV-B-5-a — PI — General 
IV-B-5-b — Submissions by the PI to NIH 
IV-B-5-C — Submissions by the PI to the 
IBC 
IV-B-5-d — PI Responsibilities Prior to 
Initiating Research 
IV-B-5-e — PI Responsibilities During the 
Conduct of the Research 
rV-C — Responsibilities of NIH 
IV-C-1 — Director 
IV-C-l-a — General Responsibilities of the 
Director, NIH 
IV-C-l-b — Specific Responsibilities of the 
Director, NIH 
IV-C-2— Recombinant DNA Advisory 
Committee 
IV-C-3 — The Office of Recombinant DNA 
Acitivies 
IV-C-4 — Other NIH Components 
IV-D — Compliance 
V. Footnotes and References of Sections I-IV 
VI. Voluntary Compliance 
VI-A — Basic Policy 
Vl-B — IBC Approval 
Vl-C— Certification of Host-Vector 
Systems 
VI-D — Requests for Exemptions and 
Approvals 
VI-E— Protection of Proprietary Data 
Appendix A. Exemptions Under III-D-4 
Appendix B. Classification of 
Microogranisms on die Basis of Hazard 
Appendix B-1 — Classifrcation of Etiologic 
Agents 
Appendix B-I-A — Class 1 Agents 
Appendix B-I-B — Class 2 Agents 
Appendix B-I-B-1 — Bacterial Agents 
Appendix B-I-B-2 — Fungal Agents 
Appendix B-I-B-3 — Parastic Agents 
Appendix B-l-B-4 — Viral, Rickettsial, and 
Chlamydial Agents 
Appendix B-I-C — Class 3 Agents 
Appendix B-I-C-1 — Bacterial Agents 
Appendix B-I-C-2 — Fungal Agents 
Appendix B-I-C-3 — Parasitic Agents 
Appendix B-I-C-4 — Viral, Rickettsial, and 
Chlamydial Agents 
Appendix B-I-D — Class 4 Agents 
Appendix B-I-D-^l — Bacterial Agents 
Appendix B-I-D-2 — Fungal Agents 
Appendix B-I-D-3 — Parasitic Agents 
Appendix B-I-D-4 — Viral, Rickettsial, and 
Chlamydial Agents 
Appendix B-Il — Classification of 
Oncogenic Viruses on the Basis of 
Potential Hazard 
Appendix B-II-A — Low Risk Oncogenic 
Viruses 
Appendix B-II-B — Moderate-Risk 
Oncogenic Viruses 
Appendix B-BI — Class 5 Agents 
Appendix B-III-A — ^Animal Disease 
Organisms Which are Forbidden Entry 
into the United States by Law 
[ 438 ] 
