Attachment II - Page 36 
50890 Federal Register / 
foreign genetic material. Human 
intervention, in this context only 
accelerates the rate of occurrence and 
captures variation produced by 
mutation. 
On the other hand, it may be argued 
that mutation plus selection techniques 
involve chemical processing that 
fundamentally alters the gene pool of 
the population of manipulated 
organisms, even though the gene pool 
has not been expanded by addition of 
foreign genetic material. Undirected 
mutation depends on chemical or other 
techniques that randomly and 
artificially induce changes in genetic 
material at a radically accelerated rate. 
Selection is used to preserve changes 
that might have been eliminated by 
natural processes. Therefore, this 
process may lead to microorganisms 
that have been fundamentally altered, 
resulting in quantitative or qualitative 
differences in functions unlikely to occur 
in nature. These arguments would lead 
to the conclusion that the techniques 
produce organisms which are "new” and 
hence subject to PMN. 
EPA seeks comment on whether 
organisms produced by undirected 
mutagenesis are appropriately 
considered new, or whether there is a 
way to distinguish between new and 
naturally occurring organisms within 
this group. (Unit UI.C of this notice 
discusses other authorities besides PMN 
that could be used to address mutated 
microorganisms; Unit 1II.D.4 discusses 
alternatives for addressing the Inventory 
status of new substances already in 
commerce.) 
v. Naturally occurring 
microorganisms. Microorganisms found 
in nature and used commercially 
without deliberate genetic intervention 
clearly are not "new chemical 
substances." In addition, EPA believes 
that microorganisms developed solely 
through techniques of artificial selection 
should be considered naturally 
occurring. Artificial selection techniques 
impose conditions on the growth of 
naturally occurring microorganisms with 
the aim of favoring the multiplication of 
a particular organism that possesses a 
desirable trait. These variations result 
from spontaneous mutations or natural 
genetic recombinations. Because the 
individual mutations occur without 
human intervention, and because it is 
difficult to define which selection 
pressures should be considered 
artificial, EPA does not believe it is 
feasible or appropriate to consider 
microorganisms produced through these 
techniques as new. However, the 
Agency requests comments on this 
'uestion. 
Vol. 49, No. 252 / Monday, December 
3. Chemical substances produced by 
genetically engineered organisms. In 
many cases, genetically engineered 
organisms will be used to produce 
chemicals, such as amino acids, 
peptides, proteins, enzymes, and 
biopolymers. When these substances 
are not listed on the TSCA Inventory, 
they are subject to PMN requirements. 
However, many chemical substances 
that are likely to be made in the future 
by genetically engineered 
microorganisms are already listed on the 
TSCA Inventory (e.g., methane, 
methanol, bacterial amylase, L- 
phenylalanine), because they are now 
produced by conventional methods. An 
argument could be made that these 
substances are new if produced by 
genetically engineered organisms, 
regardless of whether substances of the 
same name, made by conventional 
methods, are listed on the Inventory. 
However, EPA is not proposing at this 
time that chemical substances produced 
by genetically engineered organisms 
should be differentiated from existing 
products made by conventional 
methods. 
The Agency recognizes that chemical 
substances produced by genetically 
engineered organisms could in some 
respects differ from the substances of 
the same name produced by other 
methods — for example, they could have 
different impurities. However, EPA 
anticipates that risks, such as those 
associated with impurities, can be 
adequately addressed through PMN 
review of the organism used to make the 
chemical substance. In reviewing a PMN 
on a microorganism used to produce a 
commercial product, EPA will pay 
special attention to any risks associated 
with residual organisms, organism 
fragments, or other impurities present in 
the final product. EPA will be able to 
use its section 5 authority to require 
data on these risks and to regulate the 
product purity, where necessary. 
At the same time, EPA retains the 
option of defining substances produced 
by genetically engineered organisms as 
new, because the Agency is not yet 
certain whether the potential impurities 
in these substances will in fact always 
be reviewed by EPA through other 
mechanisms. For example, animal and 
plant cells used to produce new 
products are not subject to PMN under 
the proposed approach (refer to Unit 
III.A.3). If such cells were used to 
produce a product already on the 
Inventory, the Agency would not receive 
a PMN on the cells, and would not be 
able to review the product for potential 
risks or impurities associated with the 
manufacturing process. Therefore, the 
31, 1984 / Notices 
Agency requests comment on the 
adequacy of its proposed approach. 
EPA could define substances 
produced by genetically engineered 
organisms as new by generically 
modifying all Inventory listings to 
exclude substances produced by 
genetically engineered organisms. In this 
case, PMNs would be required for 
substances produced by genetically 
engineered organisms, even if chemical 
substances with the same name (but 
produced by conventional methods) 
were listed on the Inventory. Once PMN 
review was completed, the substance 
would be listed on the Inventory by 
process as well as composition. 
Authority to narrow existing 
Inventory definitions in this way is 
provided by § 710.1(a) of the Inventory 
reporting rules, which states that "EPA 
. . . will revise the categories of 
chemical substances [on the Inventory) 
and make other amendments as 
appropriate." EPA has generally 
maintained that it can narrow or 
otherwise modify Inventory listings 
under this section, as long as in so doing 
it does not require PMN review of 
chemical substances already in 
commerce. To avoid this possibility, the 
Agency, as part of any action to exclude 
products of genetically engineered 
organisms from the Inventory, would 
request the public to identify 
commercial chemical substances 
already being produced by genetically 
engineered microbes and would retain 
them on the Inventory. 
In conclusion, EPA is not proposing at 
this time to amend the Inventory to 
differentiate products of genetically 
engineered organisms from substances 
produced by conventional methods. The 
Agency believes that (a) many of these 
products will be new under any 
definition and therefore will be subject 
to PMN requirements regardless, (b) in 
most other cases, PMN review of the 
new organism will be adequate to 
address risks associated with the 
synthesis and use of existing products, 
and (c) it could be administratively 
difficult to narrow the existing listings 
without inadvertently delisting existing 
genetically engineered substances. 
Nevertheless, EPA intends to consider 
this option if it finds that information 
provided in PMNs on the products of 
genetically engineered microorganisms 
is generally inadequate, that substances 
which could cause impurities are in fact 
not subject to PMN review, or that the 
PMN review of products of genetically 
engineered organisms will substantially 
add to public or environmental 
protection. Public comments on this 
issue are welcomed. 
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