Attachment II - Page 38 
50692 Federal Register / VoL 49, No. 252. / Monday, December 31. 1964 / Notices 
microorganisms" under section 5 of 
TSCA will exclude some types of 
organisms and will therefore not 
address all potential risks. Ln particular, 
the approach outlined in this notice does 
not provide for PMN review of naturally 
occurring organisms introduced into 
environments where they are not native 
(nonindigenous microbes). In addition, 
organisms produced through some 
techniques for manipulating organisms 
(such as undirected mutagenesis and 
artificial selection) may not be covered 
under PMN, depending on the policy 
that EPA finally adopts. Under some 
circumstances, these organisms could 
involve risk to human health or the 
environment. In fact, the examples of 
environmental problems from 
microorganisms involve naturally 
occurring, nonindigenous forms 
introduced into new ecosystems (such 
as the Dutch elm disease). If concern 
warrants it these or other risks not 
covered under PMN review could be 
addressed under the discretionary 
authorities of TSCA, such as the 
significant new use provisions of section 
5(a)(2). 
Section 5(a)(2) authorizes EPA to 
determine by rule that a use of a 
chemical substance is a “significant new 
use.” Once a significant new use rule is 
promulgated for a specific substance or 
category of substances, companies are 
required to notify EPA 90 days before 
manufacturing or processing the 
substance for that use. As a result, EPA 
would be able to review risks associated 
with the new use before it occurred. 
This authority could be used to extend 
PMN-like coverage where concerns for 
potential risks warrant For example, if 
concern for certain new commercial 
uses of nonindigenous (exotic) 
microorganisms is sufficient EPA could 
define these uses as "significant” 
Similarly! if organisms produced through 
undirected mutagenesis are determined 
to be naturally occurring and therefore 
not subject to PMN, and if it appears 
that they may pose potential risks, EPA 
could address these organisms through a 
significant new use rule. 
EPA is not now proposing to begiria 
significant new use rulemaking for 
microorganisms. However, the Agency 
believes that this authority may prove 
useful in ensuring review of specific 
applications of microbes not covered by 
PMN requirements, and requests public 
comment on the need for such rules. 
D. Implementation Issues 
1. PMN requirements — a. Effective 
date. After reviewing public comments, 
EPA intends to issue a statement of 
policy, to be published in the Federal 
Register. This policy will identify which 
products of biotechnology are subject to 
PMN requirements and will announce 
an effective date for the requirement 
The notice will also address the status 
of an “new” substances already In 
commerce. Under various alternatives 
EPA is considering, companies 
producing such organisms would be 
required to report their substances to the 
Inventory or submit a new PMN within a 
specified period of time. These 
alternatives are discussed in paragraph 
b below. 
b. Status of substances now in 
commerce. Although EPA does not 
believe that microorganisms developed 
through recombinant or other advanced 
techniques of genetic engineering are 
now being used for activities subject to 
TSCA, it recognizes that microorganisms 
developed through less advanced 
techniques, such as undirected 
mutagenesis, are being used for TSCA 
purposes. Examples of such activities 
include use of microorganisms for watei 
pollution control and production of 
commercial chemicals. In fact, the 
Agency has reason to believe that 
hundreds or even thousands of mutated 
strains are now being sold or offered for 
sale in commerce for non-drug, non- 
food, and non-pesticidal applications. If 
EPA determines that new substances 
produced through these techniques will 
be subject to PMN, it will have to 
develop an equitable approach to 
handling substances already in 
commerce. 
EPA believes that the most 
appropriate approach may be to allow 
companies to report genetically 
engineered substances already in 
commerce for the TSCA Inventory 
without going through PMN. This might 
be done either through voluntary 
reporting (which might be appropriate if 
only a few companies were affected), or 
through a rule under TSCA section 8 (a) 
and (b), EPA's authority for compiling 
and keeping current an Inventory of 
existing chemicals. The Agency believes 
that this approach is appropriate 
because its interpretation of the 
applicability of TSCA to biotechnology 
is relatively recent, and companies may 
have entered this area believing in good 
faith that they were not subject to PMN. 
An alternative would be to require 
PMNs from companies for any "new” 
organisms now in commerce. While this 
approach would mean that EPA would 
review these organisms under the PMN 
authority, it is not consistent with the 
preventive function of section 5 — the 
uses subjedt to PMN notification would 
already have occurred — and could be 
extremely burdensome on industry and 
EPA's review resources. Therefore, EPA 
does not favor this alternative. EPA 
requests comments on these and other 
approaches to handling "new" 
organisms already in commerce, 
particularly with respect to their 
practical implications and their 
implications for health and the 
environment. 
c. PMN rules and form. EPA issued a 
final PMN rule published in the Federal 
Register of May 13, 1983 (48 FR 21722) 
and clarified it in a notice published in 
the Federal Register of September 13, 
1983 (48 FR 41132). EPA is revising 
several provisions of the rule — relating 
to the conditions of the R&D exemption 
and to data requirements in PMNs. It 
expects to propose revised language in 
the near future. 
The PMN rule defines the chemical 
substances that are subject to 
notification requirements, specifies 
information requirements, establishes 
procedures for handling confidential 
business information, establishes EPA 
review procedures, and implements 
other provisions of section 5. EPA 
believes that in most respects these 
requirements are appropriate for PMNs 
on new microorganisms. However, 
certain aspects of the rule and the 
guidance given by EPA in the preamble 
may not apply. In particular, EPA does 
not believe that the PMN form required 
by the rule will be useful either to 
submitters of notices on new organisms 
or to the Agency. Therefore, it would not 
expect PMN submitters to use this form. 
In the future, EPA expects to develop 
generalized guidance for persons 
submitting PMNs on new 
microorganisms. In any case, however, 
companies would be encouraged to 
contact OTS well before submission of a 
PMN for more specific guidance on the 
level of data appropriate for the notice. 
Unit IIIJs of this notice describes in 
general terms the kind of information 
EPA would expect to see in a PMN on a 
new genetically engineered organism. 
EPA recognizes that there is a growing 
commercial enterprise that supplies 
biotechnology research reagents, 
including commercial production of 
vectors, linkage sequences, reagents for 
nucleic acid synthesis, etc. As long as 
these substances are sold solely for use 
in R&D activities by the companies 
purchasing them, they would be exempt 
from PMN. This is consistent with 
treatment of other research chemicals 
under TSCA (see PMN rule, 48 FR 21722, 
and clarification, 48 FR 41132). 
EPA requests comments on the 
applicability of other aspects of the 
PMN rule to new biotechnology 
products. 
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