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The US EPA's Naming Conventions for New Chemical Substances Produced from Organisms

Date: Mar 23, 2009

The regulatory determination of whether or not a chemical substance is "new" for purposes of the Toxic Substances Control Act (TSCA) primarily turns on the formal chemical index name that accurately describes the substance and whether the name is listed on the TSCA Chemical Substances Inventory (Inventory). Apply these factors to the emerging area of genetically modified organisms containing transgenes (GMOs) and industrial products made from them, and the distinction between "regular" chemistry and "regulatory" chemistry is quickly apparent.

As with any new chemical substances, the Environmental Protection Agency's (EPA's) guidance for naming new chemical substances under the premanufacture notification (PMN) provisions of Section 5 of TSCA should be used when determining the name of a GMO and products produced with them. First and foremost, the EPA guidance states that chemical names "should contain all of the information known about the details of the structure and should permit the drawing of an unambiguous chemical structural diagram." Where an exact identity is not known or may be variable, one "must describe the chemical substance as completely as possible."[1] In addition to the requirement for the chemical substance to be listed on the TSCA Inventory, the GMO used to produce the chemical substance also needs to be listed on the TSCA Inventory. Therefore, a proper name needs to be attached to the organism for inclusion on the TSCA Inventory.

Once a formal chemical name (and its corresponding Chemical Abstract Services Registry Number (CASRN), if available) is determined, it should be relatively easy to complete the regulatory exercise with a search of the TSCA Inventory to determine if the chemical substance is new or not. It is not that simple, however, for two reasons. First, there is an entire section of the TSCA Inventory that is not accessible to the public --- EPA can conduct a search of this portion of the Inventory if the requester demonstrates that it has a bona fide intent to manufacture. Second, as with any emerging field, care must be taken in assigning a name to begin with, to make sure the Inventory search is legitimate. In the case of a chemical substance that is produced through the use of an organism, the major issue is whether EPA will expect to see more in the name than the chemical structure, despite the agency's public guidance quoted above. In fact, when a chemical substance is produced through the use of a GMO, regulatory naming conventions may be expanding in some cases to include further descriptive aspects of how the chemical substance is produced.

What follows below is our current understanding of the EPA's naming conventions for discrete chemicals, polymers, and enzymes produced using GMOs.

A. Discrete Chemicals

Typically, EPA names discrete chemicals produced through conventional chemical reactions for the chemical structure that results from the reaction. For example, methanol derives its name from a methyl group joined to an alcohol group.

When EPA started this program, it declined to differentiate between a chemical substance produced by an organism or GMO and the same chemical substance produced by conventional chemistry. 49 Fed. Reg. 50,890 (Dec. 31, 1984). Thus far we see no change in direction from EPA in the face of mounting use of fermentation for
non-traditional production processes. Examples provided by EPA of these types of products include methane, methanol, bacterial amylase, and L-phenylalanine.

For this class of materials, the EPA recognizes that chemical substances produced by GMOs could, in some respects, differ from the substances of the same name produced by conventional chemical reactions; however, in these cases the EPA concluded that potential risks (such as those associated with residual organisms and other impurities present in the final product) could be adequately addressed when the GMO would be reviewed for registration under TSCA.

It appears that the discrete chemical substance may not be considered a new chemical by EPA even if the organism used to produce the chemical substance is a new transgenic GMO.

B. Polymers

Polymers are usually named on the basis of the precursors or monomers used to form the polymer, but the name can also be based upon the polymeric structure. For example, for polymers formed by two monomers, the name would be Monomer 1, polymer with monomer 2.

The same polymer produced from an organism may still have the same basic polymeric structure based on the putative monomers, however, the monomers may never have actually existed as such in the organism. As a result, this class of polymers may be identified differently than their synthetically produced counterparts. On this basis, one should not presume that an existing listing on the TSCA Inventory is suitable to establish the regulatory status of a polymer produced via fermentation or plant synthesis.

For this class of materials, EPA will consider certain additional information for possible inclusion the TSCA Inventory name, such as the source organism and the feedstocks used to ultimately generate the polymer. Thus, a polymer produced by an organism could become Monomer 1, polymer with monomer 2, from organism fermentation of feedstock(s). EPA is approaching this area cautiously, in that such a polymer name may specify one polymer produced from a specific organism, and the related TSCA Inventory listing would have the same limition and specificity. This could result in multiple listings for the same basic polymer if the polymer can be grown in a variety of organisms with a range of feedstocks. As is always the case for sound regulatory determinations, therefore, finding a TSCA Inventory listing that is close is probably not good enough.

C. Enzymes

For some time now, EPA has been considering additional features in naming enzymes for purposes of the TSCA Inventory. The expansion of the Inventory that could possibly result is daunting to think about. However, an important aspect in effect now for naming enzymes for the Inventory is that whether an enzyme is new or not may turn on whether the gene that produces the substance was altered by a genetic modification. 69 Fed. Reg. 65565 (Nov. 15, 2004). EPA states:

Source refers to the organism from which the gene encoding the enzyme was derived and the organism or manufacturing platform (e.g., the tissue culture) in which the enzyme is produced. The two sources may be the same or differ when the enzyme gene from one organism is introduced through genetic engineering into a different organism or through the use of a synthetic sequence.

69 Fed. Reg. at 65568. This statement suggests that, in the case of enzymes, EPA would view an enzyme produced from either a modified or unmodified organism as coming from the same source where the enzyme gene has not been removed or altered. In addition, EPA indicated that it would like to reference up to four features to differentiate among enzymes that currently share the same name, including the enzyme's source, enzyme's function, procedures used to isolate the enzyme, and the amino acid sequence. While it has not been formally proposed, should EPA's concept of adding features to current enzyme nomenclature be implemented, substantial differentiation of enzymes would result that does not currently exist.

D. New Transgenic GMOs

For all classes of chemical substances discussed above, the EPA considers the organisms used to produce them to fall within the definition of a "chemical substance," coming under TSCA jurisdiction. Therefore, if the organism is considered a new chemical substance, a microbial commercial activity notice (MCAN) submission may be required depending on the organism and the changes introduced into the organism.

When an MCAN is required, the MCAN needs to be crafted to allow company personnel the ability to continue to work with modifications to the organism in predictable ways without the need to file multiple MCANs for similar organisms. Any change in organism not described in the submission to EPA could otherwise require a new submission.

Concluding Thoughts

Regulatory names for chemical substances produced by an organism are an emerging area for the industry and at the EPA. As a result, what appear to be identical chemical substances may have subtly different names, depending on the process used to produce them. Little in the way of official, written guidance currently exists. Yet manufacturers and importers are still expected to be aware of these regulatory distinctions in naming their products, to ensure proper compliance with TSCA. Under current circumstances, it makes sense to have these discussions with those with experience in these determinations and the EPA, well in advance of commercial-scale production.