Attachment II - Page 40 
50894 Federal Register / Vol. 49, No. 252 / Monday, December 31, 1984 / Notices 
whether or not the microbial product is 
genetically engineered. 
For further information on section 13 
requirements, importers should contact 
the OTS TSCA Assistance Office. 
E. Nature of EPA 's PMN Review 
OTS has prepared a background 
document describing possible 
information that could be submitted in a 
PMN on a microorganism and a plan for 
conducting PMN reviews. This 
document is available from the OTS 
Public Information Office at the address 
listed at the beginning of this notice. 
The following unit more generally 
describes the types of information and 
data that EPA would expect to receive 
in PMNs for genetically engineered 
microorganisms, and how OTS intends 
to conduct PMN reviews for these 
microorganisms. 
1. Authority to obtain information. 
Unlike pesticide and drug statutes, 
TSCA does not impose a priori testing 
requirements on new chemical 
substances. The Act requires submitters 
to provide certain information on 
chemical identity and exposure to the 
extent that it is “known or reasonably 
ascertainable" to the submitter. 
Submitters must also provide health and 
environmental test data in their 
possession or control. These basic 
information requirements are explained 
in detail in the PMN rule (48 FR 21722] 
and clarification notice (48 FR 41132). 
EPA has 90 days, extendable to 180 
days for good cause, to review the data 
submitted on a new chemical substance. 
After the review period has expired, 
manufacture may begin unless EPA has 
taken action to control the substance. 
Where information provided in a PMN is 
insufficient for a “reasoned evaluation" 
of the health and environmental effects 
of the new substance, section 5(e) 
provides EPA with authority to ban or 
regulate the substance, pending the 
development of data. To invoke this 
authority, EPA must find (a) that the 
substance may present an unreasonable 
risk, or (b) that the substance will be 
produced in substantial quantities, and 
it may reasonably be expected to enter 
the environment in substantial quantity 
or there may be significant or 
substantial human exposure to it 
(section 5(e)(l)(A)(ii){II).) 
EPA believes that this section 
provides adequate authority to control 
potential risks where specific concerns 
are identified or exposure may be 
significant. Because of the high degree of 
uncertainty associated with the use of 
genetically engineered organisms in the 
environment, there may be insufficient 
data from which to extrapolate or 
estimate risks. Also, because the 
organisms may reproduce and grow in 
the environment, the release of 
relatively small quantities may lead to 
substantial exposure. Therefore, in 
cases where data are insufficient for a 
reasoned evaluation of the risks and 
where even relatively limited amounts 
are released, the section 5(e) authority 
will be an appropriate tool to obtain 
data and, if necessary, to regulate 
genetically engineered organisms used 
for commerical purposes. 
To avoid unnecessary action under 
section 5(e) or other authorities, persons 
likely to be subject to PMN requirements 
should consult EPA early to identify 
data and other information that might be 
developed for a PMN. Information needs 
are discussed in more detail below and 
in a background document 
accompanying this notice. 
2. Types of information required. 
Because of the wide variety of 
microorganisms and applications likely 
to be reviewed in the PMN program, and 
the absence of generally accepted 
principles of risk assessment for 
genetically engineered microorganisms. 
OTS does not believe that rigid guidance 
on minimum data is appropriate. For the 
foreseeable future, OTS intends to 
decide the level of information 
appropriate for a “reasoned evaluation" 
of engineered organisms on a case-by- 
case basis. However, as the Agency 
gains experience in the review of 
nonindigenous and genetically 
engineered microorganisms and their 
products under both TSCA and FIFRA, 
and with the development of risk 
assessment methods, EPA believes that 
it will be possihle and desirable to 
develop more specific guidelines on the 
level of test data and other information 
that might be submitted and how these 
data might be used in the evaluation of 
products of biotechnology. 
Data necessary for assessment of a 
microorganism will vary according to 
the risk potential of the organism. For 
example, OTS would generally need 
more definitive data on the use of a 
genetically engineered microbe in the 
open environment than in a closed 
system. Similarly, the Agency would 
generally expect more information on 
organisms that survive and reproduce 
than for those that will not survive in 
the environment, or that can be 
effectively contained. The Agency 
would be more concerned and would 
expect more information if the parent or 
subject organism is pathogenic or toxic 
to humans, plants, animals, or other 
microbes; if the parent or subject 
organism has a function that is 
ecologically disruptive (eg., organisms 
which are extremely competitive for 
common organic substrates in soil); if 
the parent or subject organism has a 
poorly characterized genome; or if the 
genetic material is unstable or could be 
transmitted to other organisms. 
In all cases, OTS would expect 
enough information to identify an 
organism unambiguosly, both to support 
an assessment of risk and to hst the 
organism on the Inventory. This would 
include information on (a) sources of the 
introduced nucleic acids, (b) how the 
nucleic acids were manipulated, 
including information about hosts, 
vectors, etc, and (c) what protein or 
special function was produced. Data on 
the parent organisms and the resulting 
organisms might include physiological, 
pathological, genetic, cultural, 
taxonomic, and ecological 
characteristics. 
If an organism is intended for use in 
physically contained systems, 
information about growth conditions, 
containment methods (including 
emergency back-up systems if the 
organism is potentially harmful or might 
be inadvertently released), workplace 
exposure and worker practices, possible 
releases, and disposal might be 
appropraite. If the organism is used to 
produce commercial substances, OTS 
would expect data on the purity of the 
final product and the presence of any 
residual organisms or contaminants in 
the product. 
If the organism Is to be used in the 
environment, EPA would expect 
additional information, including 
information on intended uses, the 
manner in which the organisms will be 
applied, and descriptions of the target 
environment, including the organisms 
and ecological systems potentially 
subject to exposure. Testing in 
microcosms or other simulated 
environments may be necessary to 
answer such questions as whether an 
organism may survive, replicate, be 
transported, or exchange genetic 
material with other organisms. Factors 
that limit the mobility or survivability of 
the organisms or their genetic material 
(e.g., via genetic transfer) will also be 
significant considerations in.the risk 
evaluation. In addition, particularly 
where organisms may survive, test data 
such as those described in OPFs 
Subdivision M Guidelines, described in 
Unit II of this notice, may be 
appropriate. 
Submitters should also include 
information developed for an 
Institutional Biosafety Committee or the 
NIH RAC, or information related to 
health and environmental safety 
developed to comply with other statutes 
(for example, data developed on an 
organism originally used for food or drug 
[ 394 ] 
