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618 Subpart G—General Exemptions for New Microorganisms

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618 Subpart G—General Exemptions for New Microorganisms § 725.370 40 CFR Ch. I (7–1–11 Edition) the conditions of the proposed test porting of certain new microorganisms marketing activity. for commercial purposes. (e) Persons applying for a TME must (b) Recipient microorganisms eligible also submit the following information for the tiered exemption from review about the proposed test marketing ac- under this part are listed in § 725.420. tivity: (c) Criteria for the introduced ge- (1) Proposed test marketing activity. (i) netic material contained in the new The maximum quantity of the micro- microorganisms are described in organism which the applicant will § 725.421. manufacture or import for test mar- (d) Physical containment and control keting. (ii) The maximum number of persons technologies are described in § 725.422. who may be provided the microorga- (e) The conditions for the Tier I ex- nism during test marketing. emption are listed in § 725.424. (iii) The maximum number of persons (f) In lieu of complying with subpart who may be exposed to the microorga- D of this part, persons using recipient nism as a result of test marketing, in- microorganisms eligible for the tiered cluding information regarding duration exemption may submit a Tier II ex- and route of such exposures. emption request. The limited reporting (iv) A description of the test mar- requirements for the Tier II exemption, keting activity, including its duration including data requirements, are de- and how it can be distinguished from scribed in §§ 725.450 and 725.455. full-scale commercial production and (g) EPA review procedures for the research and development activities. Tier II exemption are set forth in (2) Health and environmental effects § 725.470. data. All existing data regarding health (h) Subparts A through C of this part and environmental effects of the apply to any submission under this microorganism must be reported in ac- subpart. cordance with § 725.160. § 725.420 Recipient microorganisms. § 725.370 EPA review of the TME appli- cation. The following recipient microorga- General procedures for review of all nisms are eligible for either exemption submissions under this part are con- under this subpart: tained in §§ 725.28 through 725.60. In ad- (a) Acetobacter aceti. dition, the following procedures apply (b) Aspergillus niger. to EPA review of TME applications (c) Aspergillus oryzae. submitted under this subpart: (d) Bacillus licheniformis. (a) No later than 45 days after EPA (e) Bacillus subtilis. receives a TME, the Agency will either (f) Clostridium acetobutylicum. approve or deny the application. (g) Escherichia coli K-12. (b) A submitter may only proceed (h) Penicillium roqueforti. with test marketing activities after re- (i) Saccharomyces cerevisiae. ceipt of EPA approval. (c) In approving a TME application, (j) Saccharomyces uvarum. EPA may impose any restrictions nec- essary to ensure that the microorga- § 725.421 Introduced genetic material. nism will not present an unreasonable For a new microorganism to qualify risk of injury to health and the envi- for either exemption under this sub- ronment as a result of test marketing. part, introduced genetic material must meet all of the criteria listed in this Subpart G—General Exemptions section. for New Microorganisms (a) Limited in size. The introduced ge- netic material must consist only of the § 725.400 Scope and purpose. following: (a) This subpart describes exemptions (1) The structural gene(s) of interest. from reporting under subpart D of this (2) The regulatory sequences permit- part, and from review under this part ting the expression of solely the gene(s) altogether, for manufacturing and im- of interest. 618 VerDate Mar<15>2010 16:57 Aug 29, 2011 Jkt 223174 PO 00000 Frm 00628 Fmt 8010 Sfmt 8010 Q:\40\40V31.TXT ofr150 PsN: PC150 Environmental Protection Agency § 725.421 (3) Associated nucleotide sequences rectly toxic to target cells, yet still ad- needed to move genetic material, in- versely affects humans. An example of cluding linkers, homopolymers, adap- a sequence which indirectly contrib- tors, transposons, insertion sequences, utes to toxic effects is the sequence and restriction enzyme sites. which encodes the portion of the botu- (4) The nucleotide sequences needed linum toxin, listed in paragraph (d)(3) for vector transfer. of this section, capable of blocking the (5) The nucleotide sequences needed release of acetylcholine from for vector maintenance. gangliosides. Botulinum toxin affects (b) Well-characterized. For introduced neuromuscular junctions by its block- genetic material, well-characterized age of acetylcholine release, leading to means that the following have been de- irreversible relaxation of muscles and termined: respiratory arrest. (1) The function of all of the products (B) It binds a toxin or toxin precursor expressed from the structural gene(s). to target human cells. (2) The function of sequences that (C) It facilitates intracellular trans- participate in the regulation of expres- port of a toxin in target human cells. sion of the structural gene(s). (ii) While these toxins are listed (3) The presence or absence of associ- (with synonyms in parentheses) in ated nucleotide sequences and their as- paragraphs (d)(2) through (d)(7) of this sociated functions, where associated section according to the source orga- nucleotide sequences are those se- nism, it is use of the nucleotide se- quences needed to move genetic mate- quences that encode the toxins that is rial including linkers, homopolymers, being restricted and not the use of the adaptors, transposons, insertion se- source organisms. The source orga- quences, and restriction enzyme sites. nisms are listed to provide specificity (c) Poorly mobilizable. The ability of in identification of sequences whose the introduced genetic material to be use is restricted. Although similar or transferred and mobilized is inac- identical sequences may be isolated tivated, with a resulting frequency of from organisms other than those listed transfer of less than 10¥8 transfer below in paragraphs (d)(2) through events per recipient. (d)(7) of this section, these comparable (d) Free of certain sequences. (1) The toxin sequences, regardless of the orga- introduced genetic material must not nism from which they are derived, contain a functional portion of any of must not be included in the introduced the toxin-encoding sequences described genetic material. in this paragraph (d). (2) Sequences for protein synthesis in- (i) For the purposes of this section, a hibitor. functional portion of a toxin-encoding Sequence Source Toxin Name sequence means any sequence which codes for a polypeptide that has one of Corynebacterium diphtheriae Diphtheria toxin & C. ulcerans the following effects: Pseudomonas aeruginosa Exotoxin A (A) It directly or indirectly contrib- Shigella dysenteriae Shigella toxin (Shiga toxin, utes to toxic effects in humans. Di- Shigella dysenteriae type I toxin, Vero cell toxin) rectly contributes to toxic effects in Abrus precatorius, seeds Abrin humans means those sequences encod- Ricinus communis, seeds Ricin ing polypeptides that have direct tox- (3) Sequences for neurotoxins. icity to target cells. An example of a sequence which directly contributes to Sequence Source Toxin Name toxic effects in humans is one which Clostridium botulinum Neurotoxins A, B, C1, D, E, encodes the portion of diphtheria F, G (Botulinum toxins, toxin, listed in paragraph (d)(2) of this botulinal toxins) section, capable of interacting with Clostridium tetani Tetanus toxin (tetanospasmin) elongation factor 2, leading to inhibi- Proteus mirabilis Neurotoxin tion of protein synthesis in target res- Staphylococcus aureus Alpha toxin (alpha lysin) piratory, heart, kidney, and nerve tis- Yersinia pestis Murine toxin sues. Indirectly contributes to toxic ef- Snake toxins Bungarus caeruleus Caeruleotoxin fects in humans means a sequence Bungarus multicinctus Beta-bungarotoxin whose encoded polypeptide is not di- (phospholipase) 619 VerDate Mar<15>2010 16:57 Aug 29, 2011 Jkt 223174 PO 00000 Frm 00629 Fmt 8010 Sfmt 8010 Q:\40\40V31.TXT ofr150 PsN: PC150 § 725.422 40 CFR Ch. I (7–1–11 Edition) Sequence Source Toxin Name (7) Sequences that are general cytotoxins. Crotalus spp. Crotoxin (phospholipase) Dendroaspis viridis Neurotoxin Sequence Source Toxin Name Naja naja varieties Neurotoxin Notechia scutatus Notexin (phospholipase) Adenia digitata Modeccin Oxyuranus scutellatus Taipoxin Aeromonas hydrophila Aerolysin (beta-lysin, Invertebrate toxins cytotoxic lysin) Chironex fleckeri Neurotoxin Clostridium difficile Cytotoxin (toxin B) Androctnus australis Neurotoxin Centruroides sculpturatus Neurotoxin Clostridium perfringens Beta-toxin; Epsilon-toxin; Kappa-toxin (4) Sequences for oxygen labile Escherichia coli & other Cytotoxin (Shiga-like toxin, cytolysins. Enterobacteriaceae spp. Vero cell toxin) Pseudomonas aeruginosa Proteases Sequence Source Toxin Name Staphylococcus aureus Gamma lysin (Gamma toxin); Enterotoxins (SEA, SEB, Bacillus alve Alveolysin SEC, SED SEE); Bacillus cereus Cereolysin Pyrogenic exotoxins A B; Bacillus laterosporus Laterosporolysin Toxic shock syndrome tox- Bacillus thuringiensis Thuringiolysin ins (TSST-1) Clostridium bifermentans Lysin Staphylococcus aureus & Leucocidin (leukocidin, Clostridium botulinum Lysin Pseudomonas aeruginosa cytotoxin) Clostridium caproicum Lysin Streptococcus pyogenes Streptolysin S (SLS); Clostridium chauvoei Delta-toxin Erythrogenic toxins (scarlet Clostridium histolyticum Epsilon-toxin fever toxins, pyrogenic Clostridium
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