Regulation, of Genetically Engineered
Substances under TSCA
March 1383
DISCLAIMER
This document is a preliminary draft, and has not been
peer and administratively reviewed within EPA. It should
not be construed to represent Agency policy.
Chemical Control Division
Office of Toxic Substances
Office of Pesticides and Toxic Substances
United States Environmental Protection Agency
Washington, D.C.
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CONTENTS
•—.
1. Introduction •>....»»..». ............. »».......» ......I
2. Background Relevant to TSCA .........................................5
3. Potential Health, and Environmental Concerns ..»».....«.«.»8
4. Jurisdiction of TSCA »«... .» . ^.^.14
5. Role of Other Agencies, and Authorities vis-a-vis TSCA ...24
6. Implications for Review and Regulation under TSCA .......29
7. Conclusion ».»....».«..»».«»»»... -~ 33
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1, Introduct ion
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The purpose of this paper is to present the major issues
which must be investigated in order to determine whether the
Office of- Toxic Substances- (OTS) has. or should establish
regulatory responsibility in- the- developing area of
biotechnology.
The paper is. not intended to answer the numerous and very
complex questions of how TSCA might be implemented in this new
area* Rather/- it establishes-, that from a preliminary standpoint.
there appear to be good reasons, for OTS to. assume some level of
regulatory responsibility for biotechnology/ and that extensive
investigation will be necessary to work out the details.
In summaryf this paper provides the fol«iowingr
• a brief history of the biotechnology industry,
* -• -
s » .• * *
*• a broad discussion of the nature of health and
environmental concerns about the industry/
• an overview of the issues which must be analyzed in
order to determine TSCA's role in the biotechnology
area,
0 resource and information obstacles if regulation under
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TSCA is eventually to be established.
There is no generally accepted definition of
biotechnology. The Organization for Economic Cooperation and
Development (OECD), after reviewing ten different definitions,
proposed using "the application of scientific and engineering
principles to the processing of materials by biological agents to
provide goods and services*"
For purposes of this paper, biotechnology will be defined as
the manufacture, processing, distribution in commerce, use or
disposal of genetically engineered substances. I/ Thus,
regulation of biotechnology could encompass any commercial or
industrial activity having to do with genetically engineered
substances themselves, as well as products produced by
genetically engineered substances.
Biotechnology is an evolving field in which other government
agencies, private and non-profit groups (including universities,
major chemical and pharmaceutical companies, and genetic
engineering firms) have become increasingly involved. The OTS
Genetic engineering is the process of purposefully changing
the hereditary material (DNA) of a living cell(s), as opposed
to natural selection or mutagenesis which may occur without
purposeful human intervention.
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role has not yet been defined* There are questions of whether
some substances in this field may be subject to TSCA jurisdiction
at all/ and there is no clear view either of the potential risks
of such substances or the appropriate approach to their
evaluation*
Since the development, of the NIH guidelines on research
practices in this field, EPA has- expressed concerns about the
/
potential environmental impacts and health risks associated with
commercial activities/ neither of which were covered by; NIH-
However/ no EPA position has yet been formally stated or
implemented*
At the March 1982 OTS Program Reviewr the Director of OTS
requested that a paper on biotechnology be developed/ to serve as
the basis for the Office to decide what additional actions/ if _
_
any/ should be taken. In Septemberr 1982/ the Assistant Admini-
strator for Pesticides and Toxic Substances asked the Admini—
.strator's Toxic Substances Advisory Committee- to take a long-term.
look. at. the kinds of issues; the Agency might have to address if
,-*»,. * - - -,
it became involved in regulating biotechnology.
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2. Background Relevant to TSCA
Basic research on genetic engineering advanced rapidly in
the 1970s, and its quality has been recognized by the award of
several Nobel Prizes to American scientists*
U.S. industry; has begun to contribute to biotechnology
research and. to capitalize on its. results-. Large drug, chemical,
and agricultural companies have entered: into agreements with
/
universities., invested in genetic engineering firms, and created
their own biotechnology divisions. Dow, DuPont and Monsanto are
among the chemical, companies that are increasingly invested in
biotechnology. While basic research is thus continuing,, there is
increasing likelihood of commercial applications.
It Is possible to identify a number of current and potential
commercial applications that could involve the use_ of genetically
-* -
altered microorganisms or other li^ng systems. These include
the following examples (Part 5 will separate out the specific
uses or commercial activities which could fall under the
jurisdiction of. TSCA) ?
Drugs—Hormones may be produced in sufficient quantities, by
using biotechnology methods, that other production methods
(such as chemical synthesis and extraction from the glands of
dead humans and animals) would be replaced.
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Food processing—Single cell protein, from such products as
waste sawdust and methano1, may be produced more efficiently.
Mining—Microbial leaching of minerals from slag may be
•
improved.
Oil—Xanthan gum and: microorganisms for enhanced oil recovery
/
may be used*
t
Pollution control—Microorganisms may be used to degrade oil
for cleanup of oil spills..
Agriculture—Genetic engineering could be used to enhance
nitrogen fixation capabilities of crops, possibly leading to
• - • • ' _
increased production with less- use of fertilizer", in animal
husbandryr etc.
*
The greatest relevance- oft TSCA. to- biotechnology is to
. ' -
potential applications in the' chemical industry. The following
characteristics of biotechnology lead to the promise of wide
application in this industry: the ability to use renewable
resources as feedstocksr the ability to use lower temperatures
and pressures (and therefore less energy) in production
processes, the ability to simplify serial chemical processes into
one-step biological processes, and the expectation of less
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pollution because of end-product purity and fewer undesirable by-
products.
Although fermentation processes have been used for centurie1
in the production of foods and drugs, the chemical industry is
largely petroleum based and used to dealing with the physical
sciences and engineering. For this reason/, the chemical industry
is behind the- drug industry in the application of biotechnology.
Therefore, although applications that could be- subject to
regulation under TSCA may already exist or are near-term
possibilities (e.g.., genetically-engineered oil spill degraders),
widespread application of biotechnology in the chemical industry
(i.e., major changes in the- methods of production) may not occur
for some time. Of course, applications which would require TSCA
jurisdiction cannot be accurately predicted at this point in
time. Therefore,, applications must be continually monitored as
they evolve/ in order for OTS to anticipate its future
responsibilities*
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4. Potential Health and Environmental Concerns
The major public fears associated with genetic engineering
are that purposefully or accidentally,. DNA will be changed
through means and/or with outcomes that, are unacceptable to
•
society* An additional fear is that new. strains of
microorganisms will be developed that may have adverse or even
catastrophic effects on humans or the environment*
The principal early concerns among researchers on DNA were
the potential health risks (both toxic and pathological) posed in
laboratories as the consequence of direct exposures to
genetically engineered organisms. The major actions taken to
protect against adverse health or environmental effects in
* •
laboratory research on recombinant DNA have been physical
containment of the substances and the use of'attenuated strains
of bacteria. Approved disposal and worker protection methods
have also been developed as a result of. lego.slatz.ve review, NIB
guidelines* and creation of; institutional, biosafety committees in
• '. ' '"*.'"•:•" f '-.•** »" * _ -
organizations receiving federal funds for recombinant. DNA (rDNA)
research. Thus, guidelines and oversight functions have been the
main lines of defense for the potential risks of this technology
to date, and these have focused exclusively on research-related
risks.
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The use of genetic engineering is moving increasingly from
research to industrial application. This means that the products
and uses of microorganisms are moving from small-scale settings
(containers on the laboratory bench) to large-scale development
/
and. manufacturingf and eventually to applications in plants and
in the* environment. Thusv current controls may not be adequate
to meet the potential risks to* health and the environment frcm,
purposeful or inadvertant exposure to rDNA substances. The
following are some general concerns&
(i) Use of more virulent strains* The trend in
biotechnology research is towards less concern about the
virulence of the strains used. This is partly because experience
has not led to serious negative consequences, and partly because
the health hazards and appropriate safeguards appear to be less
. . • . • - •
than those used in research on rabo.esr typhus and other virulent
substances. Most rDNA research has been done on strains of
E. coll., a, bacterium that is found in animal (including human)
intestines. Researchers are beginning to investigate using
' - ....•."
free-living and spore-forming bacteria-, and genera that are
human, plant or animal pathogens. There is limited information
concerning the survival of engineered organisms or the likelihood
of their genetic exchange with other life forms, but there is the
possibility that they could infect or cause toxicity in non-
target species, including humans.
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(ii) Research not subject to NIH guidelines» Only federally
funded (mainly NIH and NSF) research must be in compliance with
the NIH guidelines* However, a number of firms and laboratories
which are not federally funded have voluntarily agreed to abide
by the guidelines, and some regulations have been passed by State
and local governments* (Cambridge, Massachusetts* passed a law
that genetic engineering firms in that city must adhere to the
NIH guidelines.) Since the availability of private funds for
research is expected to increase, along with a tendency toward
increased secrecy on the part of companies competing to develop
new products, we may face in the future a greater degree of
independent, unmonitored research and development activities*
(iii) Inexperience with large-scale production*. As
companies that do not have exp'erience with strict containment and
other protections start producing biotechnological substances or
products on a large scale, there are increased risks of accidents
or mistakes that couJLd lead to inadvertant release of genomes,
and exposure of workers, consumers, the public and the
environment. The- risks and needed protections may be far
different from the traditional fermentation industry.
(iv) Intended dispersal in the environment» The protective
procedures and mechanisms that have been developed so far have
concentrated on containment, and specific health effects on
humans* A number of the potential applications of DNA involve
/
deliberate dispersal into the environment. Whether attenuated
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strains are used or not, there will often be new strains for
which humans may have no existing defense against adverse
effects. Additional unknowns arise when considering potential
impacts on existing ecosystems.
b« Examples of biotechnology risks _ _
Examples of specific risk scenarios that could develop in
various industries include the following (some of these problems
are also associated with conventional microorganisms):
Drugs'—There is the risk of exposure of workers and the
^^^^^^^^^^^^* •
surrounding community to aerosols containing microorganisms
developed from human pathogens, which might be able to cause
infection. Mew genetic engineering firms do not have the
experience of established drug companies in the use of
containment procedures. (Furthermore, FDA does not have
regulatory jurisdiction over drug manufacturing. OTS should
therefore consider whether it has, or should^establish,
.. " -•»" ... ' - " m f" '
• • * • - »
jurisdiction- in thii area.,)
• •
• ,
Chemicals—'Potential risks are qualitatively similar to those
seen in the drug industry. However, lack of experience in
the use of containment procedures, and the greater potential
scale of such operations, may increase the potential for
worker exposure and environmental release of genetically
engineered organisms.
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Energy—Such applications often involve the direct release of
genetically altered organisms to the environment. As in the
chemical industry, the microbes used in enhanced oil recovery
are potentially serious human pathogens.
Mineral leaching from slag- heaps—The large-scale use_of
microbes may result in natural selection of bacterial strains
that are infectious to humans. The leaching may also enhance
the generation of. sulfuric acid which could cause serious
acidification of fresh water sources*
Metal concentration from settling ponds or dilute water
streams--The use of bacteria could transform some of the
^^^^^MBHMBBMMBM* *
metals (e»g», mercury) into organometallic compounds that are
.
toxic to higher life forms and could enter the food chain in
the environment^
Waste treatment—Heavy metaL ions might.be transformed by
• • * * _ . »"
i ** ^ *».*.•
microbes into organic derivatives that are toxic to aquatic
animals that take them up from the sediments. In other
applications there is a potential public health threat from
infectious bacteria being spread through aerosols generated
by sewage treatment plants (i.e., from air bubbled through
activated sludge and sewage water splashing over rocks in
trickling filter beds). Similar risks exist for conventional
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biological treatment facilities, but the use of genetically
modified organisms may increase the concern for such risks.
Agriculture—Sewage and other forms of wastewater might be
treated by genetically altered organisms and applied as
fertilizer to croplands* This could result in harmful
aerosols and groundwater contamination. There are also risks
that genetically engineered species could transfer genetic
material to other plants, perhaps resulting in more vigorous
weeds (resulting in a need for more herbicides), increased
denitrification, increased crop disease susceptibility, and
changes in the niches and pathogenicities of plant viruses
and soil bacteria*
•
« *
In conclusion, this section has discussed some general and
some specific concerns about the risks associated with the use of
biotechnology. It should be emphasized that there is no way yet
to fully characterize these risks (if any) nor is it clear that
' *r .*..»„• --.
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these risks are significant either in absolute terms or in
^ *
relation to the potential benefits of biotechnology. The
uncertainty about the likely nature and magnitude of these risks
is very great and is one of the major factors for OTS to consider
in exploring its policy options.
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4. Jurisdiction of TSCA
There are a number of complex issues that relate to the
jurisdiction of TSCA over biotechnology. Some of these issues
are- discussed below, but definitive conclusions about TSCA's
statutory authories will require extensive research and are not.
possible based on this degree of analysis. Nonetheless, there
appear to be many reasons for OTS to assume some level of
regulatory responsibility for biotechnology.
a« Are genetically engineered substances "chemical
substances" under TSCA?
The first, issue that must be addressed is whether
genetically engineered substances are "chemical substances" under
'* • ' . "
TSCA and are therefore subject to regulation under the law.
Section 3-(2)(A) of TSCA states that/ except for the exclu-
sions in §3(2)(B), "the term 'chemical substance* means any
organic or inorganic substance of a particular molecular
- '., . • ..•".••
V. - - • •» »
identity, including—(i) any combination of such substances
*»"•"* *
occurring in whole or in part as a result of a chemical reaction
or occurring in naturef and di) any element or uncombined
radical.* The exclusions in 53(2)(B) include: (i) any mixture;
(11) any pesticide; (iii) tobacco or any tobacco product; (iv)
any material subject to the Atomic Energy Act of 1954; (v) any
article the sale of which is subject to the tax imposed by 54181
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of the Internal Revenue Code of 1954; and (vi) any food (includ-
ing poultry and poultry products, meat and meat products, and
eggs and egg products), food additive, drug, cosmetic, or device.
It seems useful to define biological substances on an
a_ priori basis as including the following three__types.
(i) Simple living organisms (microorganisms). By being
simple (e.g., including yeasts, fungi, bacteria, and viruses, but
i
perhaps not some forms of algae or protozoa), this type excludes
any organism complex enough to be identifiable as a "higher*
animal or plant* There are two sub-types of microorganisms—'
•
those that are naturally occurring and those that, are modified by
genetic engineering* This differentiation has implications both
for the Inventory and for submission of PMNs and is discussed
further below.
• • •
(ii) Derivatives of plants, animals, and micro-organisms*
These are organic substances produced by and/or derived from
living or once living plants, animals and microorganisms. There
are implications for Inventory, reporting and PMN submission based
• *.*•"**«•« •« * **
on the method of derivation*.
•
(iii) Synthetically produced organic substances that are
the equivalent of functional components or extracellular products
of plants, animals, and microorganisms. Examples would be syn-
thetic polysaccarides or enzymes produced by genetically-
engineered microorganisms.
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Biological substances can be naturally occurring (feed-
stocks, intermediates, catalysts) or they may be products and by-
products of genetic engineering*
Biological substances that are type (ii) or type (iii)
(i.e»r living organism derivatives, or synthetically produced
organic substance equivalents),, are- clearly chemical substances
under TSCA if they are- manufactured for TSCA purposes—i.e. ,
purposes that are not excluded by the law (e.g., pesticides,
food, drugs, etc.)*
The key issue is whether type (i) biological substances
•
(e.g.? microorganisms}, when used for TSCA purposes, are also
**
chemical substances under the law. There are strong arguments
for considering them to be so. First, TSCA is very clear in
•
*
being all-inclusive in its definition of chemical substances; the
\ '
'exclusions, aside from mixtures, are specific references to sub-
•
stances regulated under other Federal laws. Second, the
legislative intent of TSCA was to be the "gap-filler," so that
any substance not adequately regulated under other Federal laws
' ~ /" I >v '. * '
w'ould fail under TSCA^ jurisdiction. Third, $3(2) (A> states that
^
"the term 'chemical substance* means any... combination of
(organic) substances... occuring in nature...." Microorganisms
may be substances, even if modified by genetic engineering.
Finally, there is the precedent of including ^Unknown or
J/ariable compositions, jCpmplex reaction products, or Biological
/
materials (UVCB's) on the Inventory. Several classes of such
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materials, including bacteria, fungi, yeasts and microorganisms,
are listed on the Inventory. The Inventory reporting
instructions included guidance on the reporting of naturally
occurring substances such as bacteria, yeast and fungi.
Although it appears that living organisms are chemical
substances under TSCAr it is somewhat novel to interpret TSCA for
such substancesr because it has always been interpreted in .lie
context of non-living matter* Terms such as manufacture,
process, chemical identity, molecular structure and exposure take
on unique meanings when applied to living organisms. Other
considerations associated with review and regulation of these
substances, which will be discussed in the following parts of
this paper, will also contribute to a decision on the role of
TSCA for these substances* and/or organisms*
b. Inventory policy _
The manner in which a chemical substance is treated on the
Inventory defines to a large- extent whether the substance is
- "V ."-••." • -, -
considered "new,** thus, requiring a PMN under'TSCA. Naturally
occurring chemical substances (e.g., plants and animals) are
considered to, be on the Inventory even if they are not
specifically listed. Thus, individuals who obtain such materials
from nature (e.g., lumber, gravel, mineral ores) are not required
to submit PMN's. Because of this provision, naturally occurring
microorganisms would automatically be considered to be implicitly
on the Inventory.
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OTS has examined the status of organisms which a) exist in
nature but are cultured and grown for commercial purposes, and/or
are derivatives of naturally occurring substances, and b) are not
specifically listed on the Inventory. According to TSCA, if such
organisms are unprocessed, or processed only by manualf
mechanical, or gravitational means, they are implicitly
considered to be on the Inventory* For example, an enzyme
extracted from naturally occurring substances by manual,
mechanical or gravitational means would, itself, be considered
naturally occurring*
If the derivatives of naturally occurring substances are
produced by means such as organic solvent extraction (which might
have the potential for affecting their chemical composition and
therefore their toxicity), they are not automatically listed on
the Inventory and, if manufactured for TSCA uses, are subject to
PMN requirements. Thus, an enzyme which is extracted from
vegetable matter by means of a hexane solvent would be subject to
PMN if the enzyme were not specifically listed on the Inventory.
1.1 . •-•..'.'.•
\ > * * "
Many'organic substance- equivalents can be produced
synthetically- If these substances are not specifically listed
on the Inventory, they require a PMN if manufactured for a TSCA
use. This would include type (iii) biological substances. There
is a subsidiary issue, however, which is whether the same poly-
peptide produced by a naturally occurring or a genetically-
engineered microorganism would be considered equivalent on the
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Inventory to the extent it is a complex or biological sub-
stance. In the case of UVCBs, where the source is important in
characterizing the substance, the genetically engineered
polypeptide probably would not be considered naturally occurring
for Inventory purposes* However, this is another complex issue
which cannot, be fully resolved without further analysis* '
Currently there is no Inventory policy regarding genetically
engineered microorganisms. The Inventory Team has received some
inquiries about whether such substances should be reported, but
has deferred giving answers until a policy decision is made by
the Office.
c. Role of TSCA in research and development
TSCA provides EFA with limited authority to regulate
»
research and development in manufacturing and processing of
•
chemical substances so long as it can determine a reasonable
basis for concern* EPA also- has responsibility for coordinating
and conducting research in the area of chemical risk assessments,
. " .«."•••." -»'•. , •>.-
including the development of appropriate test methodologies. The
implications of these TSCA authorities for biotechnology are
discussed below.
Congress provided EPA with authority to regulate research
and development. It limited this authority, however, since it
did not want to overly impede innovation and recognized that
there are fewer risks generally associated with research and
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development than with later stages of manufacture and use.
Section 8(b) excludes from the Inventory chemical substances
manufactured or processed in small quantities for research,
analysis, and development of a product. Section 5(h)(3) also
excludes them from the requirements of a PMN. In both cases the
law leaves the determination of "small quantity* to the
Administrator. Generally this has not been specifically defined,
but taken to mean any amount of the substance as long as this
amount is no greater than necessary to do the research. However,
where microorganisms are tested in an ocean environment to
determine their efficacy in degrading oil slicks, or where tney
are injected into oil wells to see how well they enhance oil
recovery, this could involve a significant quantity of
material. • Furthermore, even small numbers of such organisms
could multiply, in a favorable environment, to produce a
significant population of potentially hazardous organisms. The
risks of such activities may, for this reason, also be
significant.
•-.,„•.- • . " •
Section S(h)(3) does, give the Administrator the authority to
prescribe the manner in which those who do the research and
development must be notified of "any risk to health which the
manufacturer, processor, or the Administrator has reason to
believe may be associated with such chemical substance." While
the final PMN rules prescribe the manner in which such notifi-
cation must be made, the adequacy of such notification, given the
potential risks of rONA substances, has not been evaluated.
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The situation could well arise in which significant
quantities of living organisms resulting from research are
distributed in commerce in "small quantities" for R & 0
purposes. It is an issue whether such activities and the
resulting laboratory (company or university) research could or
should be subject to regulation under §6 of TSCA. While some
risks may be adequately covered by the NIB guidelines, theae
guidelines do not consider potential environmental effects.
Uncertain risks associated with some of the products of
biotechnology research (for example organisms which can reproduce
in the environment) might warrant their exclusion from the pro-
posed low-volume exemption. Because of the uncertainties
associated with their toxicity, biopolymers were specifically
*
excluded from the proposed polymer exemption.
Unlike the previously cited sections, $6 of TSCA provides no
exclusion for research and development where the Administrator
finds that such activities will present an unreasonable risk.
Thus, the Agency has the option to take actioa under the
• s ' «%-.'"
•>• - •
authority of 56r so long as it can determine a reasonable basis
for doing so.
In the area of chemical risk assessments, the Administrator
can work with the Secretary of HEW under $27 to conduct or
finance projects "for determining and evaluating the health and
environmental effects of chemical substances and mixtures, and
their toxicity, persistence, and other characteristics which
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affect health and the environment...." EFA's Office of Research
and Development (ORD) is currently carrying out some research
that could fall under this category, but the Agency could do
significantly more research on the risks associated with TSCA
uses of biological substances, and methods to determine the
hazards and to assess the risks involved.
*
i
d» Role of TSCA in manufacture, use, workplace hazards, and
environmental contamination
To the extent biological substances are chemical substances
and used for TSCA purposesf the law provides authority to review
health and environmental impacts throughout the entire life cycle
associated with their use (except for specifically excluded
cases; refer to p»24). For example, determining acute and
*
chronic health effects of chemical substances on workers during
manufacture and use is a traditional area of TSCA concern in
reviewing new chemical substances. The type of review would be
the same for biological, substances, except that the analyses and
'.,".. • ' - - ' '
types of- concerns, would be different where- living organisms
themselves are involved. Environmental contamination and its
consequences are the largest unknowns in the use of genetically
engineered microorganisms. TSCA should probably play a key'role
in the evaluation and regulation of such risks.
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5. Role of Other Agencies and Authorities vis-a-vis TSCA
There are three considerations in determining TSCA
jurisdiction* One is statutory authority, another is need for
OTS involvement, and a third is the jurisdiction of other EPA and
governmental authorities*
a* Authorities that exclude TSCA
Section 3(2) (B) of TSCA provides guidance as to which
substances are excluded from regulation under TSCA* Among
biological substances the most important exclusions are those
which are regulated by the U.S. Food and Drug Administration
(FDA) and EPA's- Office of Pesticide Programs (OPP). However, FDA
and OPP have authority to regulate products but not their
manufacturing. Thus, a microbe that is genetically engineered to
produce a drug or pesticide may be subject to regulation under
TSCA. Also, substances regulated by these other offices but then
used for TSCA. commercial purposes would come under TSCA
1 4 ' - - '
* ».'»•'"• -
jurisdiction for those uses.
b. Other agency authorities permitting a TSCA role
depending on need
Section 9 of TSCA provides that the Administrator may provide
a report to other federal agencies based on a finding of risk.
The report must request the other agency to determine whether the
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risk could or should be reduced by talcing action under own
laws. If the other Agency agrees that there is a risk and
initiates action, or if the agency declares that the risk, does
not exist, EPA may not take action independently. Section 9 also
requires the Administrator to consult and coordinate with the
heads of other federal agencies- to avoid duplication of effort;
other federal laws are to be used to protect against possible
risk unless the Administrator determines that actions taken under
TSCA would be in the public interest.
Some of the agencies that have played or could play a role
in the area of biotechnology include the following:
*
(i) NIH, The NIH guidelines, as revised, cover laboratory
research that is federally funded. As noted earlier, many firms
and some local governments are also voluntarily complying with
.
them. The Recombiriant DMA Advisory Committee (RAC) £/ has been
•^
extending its work to cover large-scale research and some
industrial practices, alhough RAC has acknowledged that it does
not have expertise in assessing environmental risks. There is a
.*. - -
continuing controversy over the extent to which NIH and other
* •• ' *
w
authorities should or will become involved in developing
guidelines not -only for research, but for commercial development
and scale-up of biotechnology.
— A committee formed under the auspices of NIH to investigate
and report on health risks associated with genetic
engineering research.
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(ii) OSHA- OSHA has regulatory responsibility for worker
safety—both in promulgating laws and in doing inspections. It
has not been active, however, in the biotechnology field.
Section 9 of TSCA has been interpreted to mean that EPA
action will not preclude OSHA action* However, EPA is not
i
precluded from issuing regulations which affect occupational
safety and health* Also, EPA has authority under 55 to take
action because of concern for workplace risks, whereas OSHA's
authority requires demonstrable risk. Therefore, 59 does not
preclude OTS regulation of occupational risks of new chemicals.
Futhermore, biotechnology should fall under 55 provisions because
it will involve ""new* substances* Therefore, there is good
statutory justification for OTS to analyse the risks involved
and, coordinating with OSHA, see that adequate protections are
prescribed*
(iii) NIOSH. NIOSH provides back-up research and makes
recommendations to OSHA, but does not itself have regulatory
authority. Under the previous Administration, NIOSH attempted to
- . . - .. - - . - - *
develop an rONA program* It did a series of 'walk-throughs* to
- • \ - *
begin learning about industry practices and to serve as the basis
for recommendations to OSHA* It also had a contract with EPA
(which was aborted) to look at fermentation and extraction
procedures. Under the current NIOSH priority-setting system,
however, biotechnology is not included as an activity. NIOSH
«•.
only has a staff member attending RAC meetings as an observer,
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and through CDC it sponsored the ad hoc working group on medical
surveillance mentioned above.
Additional work should be done to define the appropriate
federal role in analyzing the potential risks, or determining
possible protections against risks to health or the environmentr
from non-laboratory uses of rDKA products. It is far easier in a
new than an established industry to educate managers, engineers
and other workers about the risks and protections needed—before
major investments are made rather than afterwards. Federal
agencies could play a major role in bringing this about.
c. TSCA jurisdiction vis-a-vis other EPA authorities
Section 9 of TSCA states that the Administrator shall
coordinate action taken under TSCA with other laws administered
by the Agency. Within EPA there are several other authorities
that could have responsibility for aspects of biotechnology—
e.g., air, water and drinking water. The Office of Solid Waste
has developed a Draft Manual for Infectious Waste Management
(Sept., 1982) that could be used to develop guidance under TSCA
for handling, treating and disposing of living organisms which
may have pathogenic characteristics. OPP has proposed data
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requirements for biorational pesticides that could be very useful
to OTSr as discussed elsewhere in this paper. ORO is funding
several projects related to biotechnology or protecting and
enhancing the environment; it has also provided a representative
!
to RAG, is sponsoring a series of evening seminars on
biotechnology with, the AAAS^ and will co-sponsor a conference on
the application of genetic engineering to pollution control*
In general r however,- there have not been attempts by other
EPA offices to take a lead for the agency in the area of
biotechnology- The informal working group set up by the Science
Advisor to the Assistant Administrator for Pesticides and Toxic
Substances- is increasing the level of communication in the agency
on this topic*
i
The Office of. Toxic Substances has begun a concerted effort
.
to: D^Jnalyze biotechnology issues, 2) establish and coordinate
Agency policies with respect to genetically altered substances,
t
and 3) implement these policies in OTS. OTS appears to be the
appropriate office to lead the Agency in examining EPA's eventual
« * -
role in this important* area..
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6. Implications for Review and Regulation under TSCA
a* PMN process
Genetically engineered microorganisms would be a completely
new category of chemical substance for review in the PMN
i
process* Many of the standard approaches to the review of
•conventional* chemical substance- would not be applicable. The
problem is that there- would not be a base of data or experience
from which to draw conclusions. Even if the structures of
genetically engineered organisms were exactly specified (highly
unlikely), there would be no analagous substances from which
inferences could be drawn. If the structures could not be
precisely specified, as would frequently be the case, the
uncertainty of any inferences would be enormous.
Structure activity analyses, which form the backbone of the
PMN review, will not be sufficient for analyzing risks of living
organisms. Therefore, OTS would have to treat each substance on
a case-by-case basis* Because the number of such substances
•» ' t
•
submitted is not likely to be large in the near term, the
building of an empirical OTS database would not proceed
quickly. The best OTS can do is to stay abreast of industry
developments to maximize the lead time to prepare for PMN
submissions. For example, if it seemed that a PMN would be
submitted for a substance or micro-organism that degrades oil,
staff could examine the literature and talk with researchers in
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the field to prepare themselves- A key issue for OTS to resolve
is whether, how, and what types of testing to require under S5(e)
if significant concerns are identified.
b» Test data development
OTS must anticipate- that. PMN submitters will seek guidance on
appropriate testing*, because one of the serious deficiencies in
assessing the risk of genetically engineered substances would be
the lack of relevant test data on either health or environmental
effects. The current OTS test guidance was developed for
traditional chemicals; it is not appropriate-to developing test
data on genetically engineered biological substances* The
proposed OPP guidelines on data requirements foir'biorational
pesticides (including both biochemical and microbial pest control
agents) could be a starting point for developing appropriate
guidance. The OPP guidelines have received preliminary
endorsements from outside groups that have examined them, but
they would need to be adjusted to cover the types of substances
- . ' "
and uses likely* under TSCA. This would be an appropriate subject
•
for further investigation.
c. Expertise of OTS staff
It appears that in many areas OTS would be lacking necessary
staff expertise. Based on the experience of FDA in reviewing
drugs produced through the use of rDNA, OTS would need micro-
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biologists, .biochemists and public health specialists with
current work experience in the field to do the necessary health
reviews. Also, the chemical engineering staff would need
familiarity with containment practices for pathological organisms
and the associated worker protection techniques, and the exposure
evaluation and fate staffs, would need to be able to estimate the
likely endpoints of these substances and any degradation products
once released into the environment* There would be a need for
broad-scale ecologists who could look at potential long-term,
indirect effects,, such as the effects of microbial competition on
the ecosystem and the food chain* OTS does not have staff of
this type.
**•
It could be possible- to draw on OPP staff to assist in PMN
reviews if the. number of substances involved were not great.
There are precedents 'for cooperation* of this sort on an informal
basis.
d* Risk assessment methodologies
The key problem for OTS is to develop reasonable risk
•
assessment methodologies for genetically engineered substances
and microorganisms. The unknowns are formidable, since it is not
possible to know all the potential effects to look for. Risks
may include- '(but are not limited to)r infection, transfer of
genetic material, and release of large volumes of biological
substances into the environment without knowing what their direct
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or indirect effects would be on flora or fauna. It may be
extremely difficult to evaluate the long-term and indirect
effects of such substances. Risk assessment methodologies are
therefore important to develop to prepare to deal with
genetically engineered substances* High standards of proof may
be the best safeguard*
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7. Conclusions
Biotechnology is an area with great uncertainty in many
respects. Industry is striking out in new directions to which it
must become accustomed. Many government agencies have authority
in this area* Public scrutiny is also growing. OTS is preparing
to assume its regulatory responsibilities in this field but
extensive analysis is still required.
There are many issues for OTS to consider in developing a
policy on biotechnology. First and most important is the issue
of whether microorganisms, (one of the three types of biological
substances defined earlier) should be considered chemical
substances under TSCA» This is the issue on which
TSCA jurisdiction hinges. The preliminary work done for this
• *
paper strongly suggests that genetically engineered
microorganisms and products made from them are subject to OTS
regulation where they are used for TSCA purposes. However, the
details of OTS jurisdiction* such as the appropriate statutory
authorities to use, must be carefully investigated through
„ •
internal analysis and coordination with other federal
authorities.
A secondary set of issues, also very complex/ is how EPA
should prepare for the evaluation of these substances and what
should be the nature and level of effort of OTS and Agency
actions. The possibility of regulating genetically altered
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substances/ perhaps even living organisms, poses significant and
very complex issues with which OTS has never grappled. This
includes issues like the nature and extent of possible risks; the!
time frame in which substances which TSCA might regulate will
come to market; how to coordinate TSCA action with other federal
authoritiesr and how. to mobilize Agency resources to deal with
these issues.
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