00-17072. Notice of Filing a Pesticide Petition to Establish a Tolerance for Certain Pesticide Chemicals in or on Food

AGENCY:

Environmental Protection Agency (EPA).

ACTION:

Notice.

SUMMARY:

This notice announces the initial filing of a pesticide petition proposing the establishment of regulations for residues of a certain pesticide chemical in or on various food commodities.

DATES:

Comments, identified by docket control number PF-940, must be received on or before August 7, 2000.

ADDRESSES:

Comments may be submitted by mail, electronically, or in person. Please follow the detailed instructions for each method as provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure proper receipt by EPA, it is imperative that you identify docket control number PF-940 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT:

By mail: Linda Hollis, Biopesticides and Pollution Prevention Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: [phone]; e-mail address: [e-mail].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

You may be affected by this action if you are an agricultural producer, food manufacturer or pesticide manufacturer. Potentially affected categories and entities may include, but are not limited to:

Categories	NAICS codes	Examples of potentially affected entities
Industry	111	Crop production
	112	Animal production
	311	Food manufacturing
	32532	Pesticide manufacturing

This listing is not intended to be exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in the table could also be affected. The North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether or not this action might apply to certain entities. If you have questions regarding the applicability of this action to a particular entity, consult the person listed under FOR FURTHER INFORMATION CONTACT.

B. How Can I Get Additional Information, Including Copies of this Document and Other Related Documents?

1. Electronically. You may obtain electronic copies of this document, and certain other related documents that might be available electronically, from the EPA Internet Home Page at http://www.epa.gov/​. To access this document, on the Home Page select “Laws and Regulations” and then look up the entry for this document under the “Federal Register—Environmental Documents.” You can also go directly to the Federal Register listings at http://www.epa.gov/​fedrgstr/​.

2. In person. The Agency has established an official record for this action under docket control number PF-940. The official record consists of the documents specifically referenced in this action, any public comments received during an applicable comment period, and other information related to this action, including any information claimed as confidential business information (CBI). This official record includes the documents that are physically located in the docket, as well as the documents that are referenced in those documents. The public version of the official record does not include any information claimed as CBI. The public version of the official record, which includes printed, paper versions of any electronic comments submitted during an applicable comment period, is available for inspection in the Public Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB telephone number is [phone].

C. How and to Whom Do I Submit Comments?

You may submit comments through the mail, in person, or electronically. To ensure proper receipt by EPA, it is imperative that you identify docket control number PF-940 in the subject line on the first page of your response.

1 . By mail. Submit your comments to: Public Information and Records Integrity Branch (PIRIB), Information Resources and Services Division (7502C), Office of Pesticide Programs (OPP), Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., Washington, DC 20460.

2 . In person or by courier. Deliver your comments to: Public Information and Records Integrity Branch (PIRIB), Information Resources and Services Division (7502C), Office of Pesticide Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB telephone number is [phone].

3. Electronically. You may submit your comments electronically by e-mail to: “[e-mail],” or you can submit a computer disk as described above. Do not submit any information electronically that you consider to be CBI. Avoid the use of special characters and any form of encryption. Electronic submissions will be accepted in Wordperfect 6.1/8.0 or ASCII file format. All comments in electronic form must be identified by docket control number PF-940. Electronic comments may also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

Do not submit any information electronically that you consider to be CBI. You may claim information that you submit to EPA in response to this document as CBI by marking any part or all of that information as CBI. Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2. In addition to one complete version of the comment that includes any information claimed as CBI, a copy of the comment that does not contain the information claimed as CBI must be submitted for inclusion in the public version of the official record. Information not marked confidential will be included in the public version of the official record without prior notice. If you have any questions about CBI or the procedures for claiming CBI, please consult the person identified under FOR FURTHER INFORMATION CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

You may find the following suggestions helpful for preparing your comments:

1. Explain your views as clearly as possible.

2. Describe any assumptions that you used.

3. Provide copies of any technical information and/or data you used that support your views.

4. If you estimate potential burden or costs, explain how you arrived at the estimate that you provide.

5. Provide specific examples to illustrate your concerns.

6. Make sure to submit your comments by the deadline in this notice.

7. To ensure proper receipt by EPA, be sure to identify the docket control number assigned to this action in the subject line on the first page of your response. You may also provide the name, date, and Federal Register citation.

II. What Action is the Agency Taking?

EPA has received a pesticide petition as follows proposing the establishment and/or amendment of regulations for residues of a certain pesticide chemical in or on various food commodities under section 408 of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this petition contains data or information regarding the elements set forth in section 408(d)(2); however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

List of Subjects

• Environmental protection
• Agricultural commodities
• Feed additives
• Food additives
• Pesticides and pests
• Reporting and recordkeeping requirements

Dated: June 23, 2000.

Janet L. Andersen,

Director, Biopesticides and Pollution Prevention Division, Office of Pesticide Programs.

Summary of Petition

Pursuant to section 408(d)(2)(A)(i) of the FFDCA, as amended, AgriVir, LLC has submitted the following summary of information, data, and arguments in support of their pesticide petition. This summary was prepared by AgriVir, LLC and EPA has not fully evaluated the merits of the pesticide petition. The summary may have been edited by EPA if the terminology used was unclear, the summary contained extraneous material, or the summary unintentionally made the reader conclude that the findings reflected EPA's position and not the position of the petitioner.

AgriVir, LLC

OF6113

EPA has received a pesticide petition 0F6113 from AgriVir, LLC, 1625 K Street, NW., Washington DC 20006, proposing pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 to establish an exemption from the requirement of a tolerance for the microbial pesticide in or on Indian Meal Moth Granulosis Virus commodity.

A. Product Name and Proposed Use Practices

The product which contains the microbial pest control agent which is the subject of the present petition for a tolerance exemption is “FruitGuard-V” or “NutGuard-V” (these are alternate names for the same product). This product is a biological insecticide intended to control Indian meal moth, a serious pest of various stored commodities. The product will be used as a protectant for stored, dry commodities such as dried fruits, and nuts, and for crack treatment of facilities where such commodities are handled.

The Indian meal moth (IMM), is a serious cosmopolitan pest of dried commodities. Infestation can occur at any time from harvest to eventual consumption of the commodity. IMM is estimated to be responsible for approximately 90% of the damage done to dried fruits and nuts in storage. In facilities where these types of commodities are handled, fragments and other debris from the commodities get into cracks, crevices, and other places and IMM propagates on this material. This establishes a general infestation and reservoir for the Indian meal moth in such facilities.

Control of IMM by FruitGuard-V/NutGuard-V is by means of a naturally occurring microbial pest control agent (MPCA) which is contained in the product. This MPCA is a granulosis virus (GV) which infects the larvae of the IMM. This virus is, thus, designated as Indian Meal Moth Granulosis Virus (IMMGV). The IMMGV contained in NutGuard-V/FruitGuard-V is a naturally occurring isolate of the IMMGV and has not been genetically modified.

In FruitGuard-V/NutGuard-V, the amount of IMMGV (the MPCA ion in the product) is very small in terms of weight percent. The bulk of the product is, in fact, milled wheat bran (96%+) and brewers yeast (ca. 3%) to which have been added some vitamins (0.1%) and antioxidants (0.4%). All of these carrier ingredients are either OPP List 4A inerts^[1] , are tolerance exempted under 40 CFR 180.1001, and/or are generally recognized as safe (GRAS) or otherwise approved for direct food use under 21 CFR part 184 section 184.1 subpart B pp.446-543.

The product is produced as a milled powder and has the physical appearance of a coarse, off-white to tan powder. Due to the physical characteristics of the powder and of the milled wheat bran which constitutes the bulk of the product, this product does have a potential for producing mild, temporary eye irritation. This has been tested in an eye irritation study which has been submitted by AgriVir in support of this application. The product's labeling, therefore, carries a warning in regard to eye irritation potential.

1. The product can be applied dry or in water suspension. For the latter, it is suspended in water at a concentration of from 2 oz to 4 oz per 10 gallons of water. This provides for a sprayable suspension.

2. The proposed application rate for dried fruits and for nuts is from 30 grams (1 oz) to 140 grams (5 oz) product/ton of commodity to be protected.

3. The proposed application rate for crack, crevice, and surface spot treatments is from 60 grams (2 oz) to 300 grams (10 oz) product/100 square feet.

B. Product Identity/Chemistry

1. Identity of the pesticide and corresponding residues. This is a microbial pesticide in which the MPCA is IMMGV. This is a naturally occurring insect virus which produced a pathogenic condition termed “granulosis” in larvae of the IMM. Since IMMGV cannot be propagated other than in insect larvae, the pesticide product itself consists of IMMGV viral particles contained in body parts from infected larvae, all of which is mixed in with the wheat bran diet mixture upon which the infected larvae were grown. The residues which would result are:

i. The infected larval parts containing virus.

ii. The wheat bran larval diet mixture.

2. Magnitude of residue at the time of harvest and method used to determine the residue. The rate of application for this pesticide product is from 1 oz to 5 oz product per ton of treated commodity. The product contains^> 0.01% MPCA by weight (expressed for this purpose as viral particles). The MPCA is not metabolized in or on the commodity after application. Therefore, at the maximum application rate, maximum MPCA residues will be^> 0.00013% or (^> 1.3 parts per billion (ppb)). At the lower rate of application residues will be less than 0.26 ppb.

3. Analytical method. A statement of why an analytical method for detecting and measuring the levels of the pesticide residue are not needed. No analytical method is required because:

i. This application is for a tolerance exemption.

ii. Any method which could be developed to detect IMMGV at the very low maximum levels noted above would be a molecular biology method requiring specialized equipment and procedures not readily available in enforcement laboratories.

It is noted that microbial pet control agents which do not trigger Tier II toxicology concerns do not trigger specific residue chemistry requirements. A brief summary of the identity of the microbial pest control agent IMMGV follows:

AgriVir, LLC has applied to EPA for registration of its microbial pest control product “FruitGuard-V/NutGuard-V” (these are alternate names for the same product). This is a biological insecticide intended to control IMM, a serious pest of various stored commodities. The IMM, is a serious cosmopolitan pest of dried commodities. Infestation can occur at any time from harvest to eventual consumption of the commodity. IMM is estimated to be responsible for approximately 90% of the damage done to dried fruits and nuts in storage. In facilities where these types of commodities are handled, fragments and other debris from the commodities gets into cracks, crevices, and other places and IMM propagates on this material. This established a general infestation and reservoir for the IMM in such facilities.

Control of IMM by FruitGuard-V/NutGuard-V is by means of a naturally occurring microbial pest control agent (or MPCA) which is contained in the product.

The MPCA used in NutGuard-V/FruitGuard-V is a Granulosis Virus which infects the larvae of the IMM. This virus is designated IMMGV in the balance of this summary. The MPCA contained in NutGuard-V/FruitGuard-V is a naturally occurring isolate of the IMMGV. It has not been genetically modified.

IMMGV has no hosts other than larvae of the IMM and acts by making the IMM larvae sick, rather than by a toxic mechanism (i.e., IMMGV does not produce any specific toxin which kills the larvae). IMM larvae succumb to granulosis disease due to serious damage to one of their major organs for storage of nutrients.

The above-cited products are equivalent to a technical grade of IMMGV. They are prepared without isolation of IMMGV and, as such, the MPCA which is the subject of the present petition consists, therefore, of IMMGV occlusion bodies (“viral particles”) and Indian meal moth larval parts mixed into a production larval diet containing wheat bran, brewer's yeast, vitamins, methyl paraben, and sorbic acid.

C. Mammalian Toxicological Profile

The mode of action for IMMGV in its host, the larval stage of P. interpunctella, is pathogenic in nature. IMMGV produces granulosis disease in the larvae of P. interpunctella. “Granulosis” disease is so named because cells in infected tissue sections, when observed under light microscopy, are full of minute, refractile bodies termed “granules.” The initial signs of granulosis disease occur several days after larval ingestion of the viral occlusion bodies and consist of sluggishness and loss of appetite. These initial signs are followed by a change in the appearance of the larvae. They are normally light brown and semilucent, but when infected become opaque and white. This change is the result of the massive accumulation of viral occlusion bodies in the fat body of the infected larva. The fat body is the site of intermediary metabolism in these larvae and it is in the fat body that fat, protein, and glycogen are primarily stored. The pathogenicity of IMMGV to the larva results from the mode of viral release from cells of the fat body. This release occurs by rupture of the cells of the fat body, thereby leading to degeneration and necrosis of the fat body and, ultimately, death of the infected larva. The mode of action is distinct from a toxicity based mode of action. That is, unlike some microbial pest control agents which produce endo-toxins or exo-toxins which act to kill the target pest, IMMGV produces no toxins as part of its mode of action.

IMMGV is a member of the class of insect viruses known as baculoviruses. There are two known types of baculoviruses: polyhedrosis viruses and granulosis viruses. There is currently no baculovirus known to infect or replicate in any vertebrate host. Among invertebrates, IMMGV itself has no known host other than larvae of P. interpunctella and has been shown not to cross-infect lepidopteran or other insects other than P. interpunctella.

A number of studies on the toxicity of baculoviruses, inclusive of granulosis viruses, to animals have shown that these agents produced no effects on overall health, gross or micro pathology, hematology, clinical chemistry, and antibody stimulation occur in test animals when exposure is by the oral, dermal, inhalation, and injection routes of exposure and either single exposure or repeated exposure. These studies have been published in the open literature and were submitted as part of AgriVir, LLC's petition.

Cell culture studies (submitted by AgriVir as part of its submission) have shown that IMMGV which is actively infective and pathogenic to IMM larva, does not produce cytotoxicity in nor does it replicate in or produce pathogenicity in human embryonic lung cells, human embryonic skin cells, and monkey kidney cells. These cell lines are relevant to the safety assessment of IMMGV with regard to hazard potential to humans and domestic animals because the first two (lung and skin) represent tissues which would be the first points of contact with/attack by IMMGV and the renal line is a representative of an organ which can receive parenteral exposure and which can easily harbor infections.

Due to the physical properties of the final product and of the bran carrier, the technical MPCA does have a mild, rapidly reversible eye irritation potential. An eye irritation study has been conducted to further characterize this potential. It is summarized below.

Primary eye irritation. Due to the physical properties of the final product and of the bran carrier, the technical MPCA is expected to have a mild to moderate, reversible eye irritation potential. This has been confirmed in a rabbit eye irritation study sponsored by AgriVir, LLC. Six healthy New Zealand white rabbits (4 males and 2 females) each received 0.1 mL of the IMMGV product placed into the conjunctival sac of their right eye. The upper and lower lids were held together for approximately 1 second. In each test animal, the left eye served as an untreated control. Ocular irritation was evaluated by the Draize et al. A 1 hour post-instillation six to six treated eyes showed conjunctival irritation and one to six showed irritation of the iris. No treated eyes showed corneal effects at 1 hour post-instillation. The mean irritation score for treated eyes was 11.5 out of 110 maximum possible. At 24 hrs, the incidence of treated eyes which exhibited conjunctival irritation was five to six with one to six showing irritation of the iris. Also, at 24 hrs three to six treated eyes showed some signs of corneal opacity. This was grade 1 (scattered or diffuse, details of iris clearly visible) with respect to intensity and grade 1 with respect to area (or = to 1/4 of the cornea involved) in each case. The corneal score in each eye which exhibited corneal opacity was 5 out of a maximum possible 80 for corneal effects alone. The mean irritation score at 24 hrs was 8.3 out of a maximum possible 110. At 48 hrs post-instillation, the incidence of treated eyes which exhibited conjunctival irritation was one to six with one to six also showing irritation of the iris. Also, at 48 hrs three to six treated eyes still showed some signs of corneal opacity (same animals as at 24 hrs). This was still grade 1 with respect to intensity and grade 1 with respect to area in each case. The corneal score in each eye which exhibited corneal opacity was 5 out of a maximum possible 80 for corneal effects alone. The mean irritation score at 48 hrs was 4.3 out of a maximum possible 110. By 72 hours post-instillation, no treated eyes exhibited conjunctival or irineal irritation, but two to six treated eyes still showed a minimal corneal effect (two of the animals which had exhibited the same effects at 24 hrs and 48 hrs, still scored 1 for intensity and 1 for area; therefore, 5 out of a possible 80 for each animal). The mean irritation score at 72 hrs was 1.7 out of a maximum possible 110. By day 4 (96 hrs) post-instillation, all treated eyes were free of conjuctival irritation, irineal irritation, and corneal effects. The mean irritation score at day 4 was 0 out of a maximum possible 110. The highest mean irritation score reported (11.5 at 1 hour post-instillation) would be classified as “mildly” irritating per the Draize evaluation method. This score itself would normally be classified as “minimally” irritating, but the absence of complete resolution by 72 hrs requires a one-level increase in the descriptor. The fact that the corneal effects seen were minimal in both intensity and area, were seen in only half of the treated eyes, and resolved fairly rapidly (by 96 hours) suggests that these were probably due to simple mechanical abrasion by the solid test article after instillation into the treated eyes.

D. Aggregate Exposure

1. Dietary exposure.— i. Food. The levels of residues in treated commodities will be very low. The application rates for IMMGV are from 1/5 ounces of formulated (i.e., technical) MPCA per ton of commodity to be treated. Maximum theoretical residue concentrations will not, therefore, exceed 1.3 ppb for the MPCA. The types of commodities which are potentially to be treated with IMMGV represent less than 1% of the average total daily diet. With a 2 kilograms (kg) total daily diet the maximum theoretical average dietary exposure to the MPCA is <0.026 (μg)/day. Since IMMGV is a naturally occurring insect virus, there is some, not readily quantifiable, baseline exposure in the daily diet.

ii. Drinking water. The proposed use patterns for IMMGV are for indoor food and non-food uses. Therefore, there is no potential for drinking water exposure associated with the approval of this petition.

2. Non-dietary exposure. IMMGV only has pest control utility in the treatment of commodities for control of IMM. Therefore, the only potential for non-dietary exposure is to applicators and to mixer/loaders who will use product containing IMMGV. These non-dietary exposures are not covered within the Food Quality Protection Act (FQPA) and they are expected to be low. Information already in EPA's data bases which had been cited by AgriVir, LLC indicates that workers involved with baculovirus production and use do not experience adverse effects as a result of these exposures.

E. Cumulative Exposure

Due to its mechanism of action and extremely limited host specificity, it can be reliably stated that IMMGV does not share a common mechanism of action with any other conventional, biochemical, or microbial pesticide.

F. Safety Determination

1. U.S. population. Since the available information reliably supports that IMMGV will not produce adverse effects in humans of any age as a result of exposure by ingestion, dermal contact, or inhalation, AgriVir, LLC concludes that there is a reasonable certainty that no harm to the general adult population, including sensitive individuals, will result from dietary exposure to residues which could occur as a result of approval of this petition.

2. Infants and children. Since the available information reliably supports that IMMGV will not produce adverse effects in humans of any age as a result of exposure by ingestion, dermal contact, or inhalation, AgriVir, LLC concludes that there is a reasonable certainty that no harm to infants and children will result from dietary exposure to residues which could occur as a result of approval of this petition.

G. Effects on the Immune and Endocrine Systems

There is no reliable information to indicate that IMMGV has a potential to produce adverse effects on the immune or endocrine systems. In fact, the available studies establish that IMMGV is essentially biologically inactive in any organism other than its natural host, the larva of the Indian meal moth. Due to the natural occurrence and endemic infestation of dry commodities by the IMM, IMM larval parts and the IMMGV are historically a part of the human diet (although one of which most persons are unaware). Animal safety studies on a closely related granulosis virus (which have been submitted by AgriVir, LLC as part of the support for its registration application and the present tolerance exemption petition) showed, that after inhalation exposure of guinea pigs to an atomized mist containing 2 x 10¹¹ granulosis virus (GV) particles (“granula”)/L of air, no antibodies to the granula were observed to form and no changes in blood proteins were found. Also, there were no signs of toxicity or other adverse effects noted during the 21-day post-exposure observation period. On pathology, no irritation of lungs or airways was found. This study further supports lack of an IMMGV hazard potential with regard to the immune system. In a different study with the same closely related GV, multiple dose feeding of a total of 5 x 10¹¹ granula/mouse, divided into 34 equal doses given every third day over 99 days produced:

1. No signs of toxicity or other adverse effects.

2. No effect on hematology parameters when checked at 45 days and at 99 days.

3. No remarkable pathology findings on terminal sacrifice.

4. No evidence for increased chromosome aberrations were found. This study further supports the lack of an IMMGV hazard potential with regard to the endocrine system.

H. Existing Tolerances

There are no existing tolerances for IMMGV (the MPCA). The present petition is for the establishment of an exemption from a tolerance.

All of the intentionally added inerts in NutGuard-V/FruitGuard-V are either OPP List 4A inerts, are tolerances exempted under 40 CFR 180.1001, and/or are GRAS or are otherwise approved for direct food use under 21 CFR part 184 section 184.1 subpart B pp. 446-543. Therefore, all of the inert ingredients in FruitGuard-V/NutGuard-V are already tolerance exempted and/or are cleared for indirect food contact as a result of their incidental entry into commodities.

I. International Tolerances

There are no Codex maximum residue levels established for residues of IMMGV. IMMGV containing products are presently not registered for pest control outside of the United States.

Footnotes

1.  Per U.S. EPA/OPP: “List 4A inert ingredients are considered to be minimal risk inert ingredients. List 4A is generally reserved for those substances that are common foods or substances that are ubiquitous in nature and are not expected to present a hazard to human health or the environment.”