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Indoxacarb (DuPont). March 21,
2002. Registration approval of
Avaunt Insecticide in New York State.
New York State Department of Environmental Conservation
Division of Solid & Hazardous Materials
Bureau of Pesticides Management
Pesticide Product Registration Section
625 Broadway, Albany, New York 12233-7257
Phone 518-402-8768 FAX 518-402-9024
March 21, 2002
CERTIFIED MAIL RETURN RECEIPT REQUESTED
Ms. Miriam Carr
E.I. du Pont de Nemours and Company, Inc.
DuPont Crop Protection Stine-Haskell Research Center (S300/427)
P.O. Box 30, 1090 Elkton Road
Newark, Delaware 19714-0030
Dear Ms. Carr:
Re: Registration of DuPontTM AvauntĘ Insecticide (EPA Reg. No. 352-597) Containing the New Active Ingredient Indoxacarb
The New York State Department of Environmental Conservation (Department) has completed review of the application (received 05/04/01) and supplemental information supplied to date regarding registration of the referenced pesticide product in New York State. DuPontTM AvauntĘ Insecticide (EPA Reg. No. 352-597) contains the new active ingredient indoxacarb. As discussed in this letter, the acceptable AvauntĘ labeling accompanying the issuance of this registration must bear the text "Not for use or sale in Suffolk and Nassau Counties, Long Island, New York."
On October 4, 2001, the subject application and data package were deemed complete for purposes of technical review following one determination of incompleteness (07/03/2001). Pursuant to the review time frame specified in Environmental Conservation Law (ECL) Ą33-0704.2, a registration decision date of March 3, 2002 was established. By mutual agreement, the registration decision date was subsequently waived in order to accommodate the preparation and review of revised labeling submitted in response to issues identified in the environmental fate risk assessment.
AvauntĘ Insecticide, containing 30% indoxacarb, is labeled for foliar spray application to apples, broccoli, cabbage (tight headed varieties only), cauliflower, corn (sweet), lettuce (head and leaf varieties), pears, peppers (bell and non-bell) and tomatoes only in commercial and farm plantings for the control of certain insects. During the technical review process, DuPont submitted amended product labeling bearing additional crops uses, i.e., brussels sprouts, Chinese broccoli, Chinese cabbage, Chinese mustard cabbage, eggplant, and kohlrabi. The maximum seasonal use rate on apples and pears is 24 ounces AvauntĘ (0.44 lb. indoxacarb) per acre per crop. The remaining labeled crops have a maximum seasonal use rate of 14 ounces AvauntĘ (0.26 lb. indoxacarb) per acre per crop.
The Department conducted toxicological, ecological effects and environmental fate risk assessments for indoxacarb and the AvauntĘ formulation.
TOXICOLOGICAL RISK ASSESSMENT: Indoxacarb is a mixture of two isomers, of which only one has insecticidal activity. Indoxacarb was originally manufactured as a 50:50 mixture of these two isomers and was denoted as DPX-JW062. Subsequent production led to the active ingredient DPX-MP062, enriched to approximately 75:25 for the insecticidally active isomer. This enriched mixture (also referred to as indoxacarb) is the active ingredient in the formulated end product, AvauntĘ Insecticide. In consultation with the United States Environmental Protection Agency (USEPA), the registrant conducted a series of "bridging" studies on DPX-MP062 to demonstrate its toxicological equivalence to DPX-JW062. Therefore, the database to support registration of the AvauntĘ product is comprised of studies conducted on DPX-MP062 or DPX-JW062.
Neither indoxacarb nor AvauntĘ Insecticide was very toxic in acute dermal or inhalation studies in laboratory animals. Also, neither material was very irritating to the eyes or skin (tested on rabbits). On the other hand, whereas the AvauntĘ product was not very toxic via the oral route of exposure, the active ingredient indoxacarb was moderately toxic, particularly to female rats. In addition, the AvauntĘ product was not a dermal sensitizer (tested on guinea pigs), but the active ingredient showed some skin sensitizing properties. Indoxacarb also showed some neurotoxicity after acute exposures in rats. A decrease in motor activity occurred in females after a single dose of 100 milligrams per kilogram body weight (mg/kg); the no-observed-effect level (NOEL) was 50 mg/kg.
Indoxacarb caused some toxicity in chronic animal feeding studies. In a chronic feeding/oncogenicity study in mice, indoxacarb caused decreased body weight, body weight gain and clinical signs indicative of neurotoxicity (abnormal gait and head tilt) at 14 mg/kg/day and 20 mg/kg/day for males and females, respectively; the respective NOELs were 2.6 and 4.0 mg/kg/day. In rats chronically fed indoxacarb, decreased body weight, body weight gain and food consumption were observed in males at 10 mg/kg/day and in females at 3.6 mg/kg/day. Also observed in females at this same dose were decreased hematocrit, hemoglobin and red blood cells; the NOELs for male and female rats were 5.0 and 2.1 mg/kg/day, respectively. In dogs, decreased hematocrit, hemoglobin, red blood cells and increased absolute and relative liver weights were reported at 18 and 19 mg/kg/day in males and females, respectively; the respective NOELs were 2.3 and 2.4 mg/kg/day. The USEPA, Office of Pesticide Programs established a reference dose (RfD) of 0.02 mg/kg/day based on a NOEL of 2.1 mg/kg/day in the chronic feeding/oncogenicity study in rats, as well as in a supporting subchronic study in rats, and an uncertainty factor of 100. This RfD has not yet been adopted by the USEPA's Integrated Risk Information System (IRIS).
Indoxacarb caused some developmental toxicity in the offspring of pregnant rats and rabbits, but only at doses that also caused maternal toxicity. In one rat developmental toxicity study, a decrease in fetal weights was observed at 4.0 mg/kg/day; the NOEL was 2.0 mg/kg/day. Maternal toxicity characterized by decreased mean maternal body weights, body weight gains and food consumption occurred at 4.0 mg/kg/day with a NOEL of 2.0 mg/kg/day. In a second rat developmental toxicity study, decreased numbers of live fetuses per litter were reported at 100 mg/kg/day; the NOEL was 10 mg/kg/day. The same dose of 100 mg/kg/day was associated with maternal toxicity effects (increased mortality, decreased mean body weights, body weight gain and food consumption); the NOEL was 10 mg/kg/day. No teratogenic effects were noted in either rat study. In rabbits, reduced fetal body weights and reduced ossification of the sternebrae were reported at 1,000 mg/kg/day; the NOEL was 500 mg/kg/day. Maternal toxicity (slight decrease in maternal body weight gain and food consumption) also occurred at 1,000 mg/kg/day with a NOEL of 500 mg/kg/day. In a two-generation reproduction study in rats, no reproductive effects were observed at the highest dose tested, which was 6.4 mg/kg/day. However, maternal toxicity characterized by reduced body weight gains, body weights, food consumption and increased spleen weights occurred at a dose of 4.4 mg/kg/day; the NOEL was 1.5 mg/kg/day.
Indoxacarb did not cause oncogenic effects in either rat or mouse chronic feeding studies. It also was negative in a number of genotoxicity studies. The USEPA classified indoxacarb as "not likely" to be carcinogenic to humans.
The USEPA established tolerances for indoxacarb residues in or on apples at 1.0 part per million (ppm); brassica (5.0 ppm); corn, sweet forage (10.0 ppm); lettuce, head (4.0 ppm); lettuce, leaf (10.0 ppm); pears (0.2 ppm) and fruiting vegetables (0.5 ppm). Estimated acute dietary exposures to these residues were 33 percent of the acute population adjusted dose (aPAD) for females 13 years and older (aPAD of 0.02 mg/kg/day) and 10 percent or less of the aPAD (0.12 mg/kg/day) for the general population, infants and children ages 1 through 6 years old. These estimates used anticipated residue levels from field trial data, processing factors (where applicable) and 100 percent crop treatment assumptions. The USEPA estimated that chronic dietary exposure to indoxacarb residues would be less than 28 percent of the chronic population adjusted dose (cPAD) of 0.02 mg/kg/day for the general U.S. population, less than 37 percent for all infants less than one-year old and 73 percent for children one to six years old. This chronic exposure analysis is based on the conservative assumption that 100 percent of crops are treated and contain tolerance level residues.
The registration package contained several evaluations by the USEPA and the registrant on dermal and inhalation exposure of workers to indoxacarb. Application of the AvauntĘ product may occur up to four times per growing season. For commercial handlers wearing long-sleeved shirt, long pants and gloves (required by the label), margins of exposures (MOEs) were estimated to range from 930 to 4,200 for dermal exposure and from 600 to 11,000 for inhalation exposure. These estimates are conservative in that they are based on application to cotton fields of 476 to 1200 acres per day. Crops grown in New York State are likely to pose less exposure and risk. Initial estimates of post-application exposure from various activities on the labeled crops identified that hand harvesting and/or thinning of apples, sweet corn and tomatoes did not provide adequate MOEs at proposed labeled use. As a result, label changes (e.g., reduced number of allowed applications, longer pre-harvest intervals) were implemented to mitigate these risks. Estimated MOEs for post-application activities were then revised and range from about 100 to 925. Generally, the USEPA considers MOEs of 100-fold or greater to provide adequate worker protection.
There are no chemical specific federal or State drinking water/groundwater standards for indoxacarb. Based on its chemical structure, this compound falls under the 50 microgram per liter New York State drinking water standard for unspecified "organic contaminants" (10 NYCRR Part 5, Public Water Systems).
The available information on indoxacarb and AvauntĘ Insecticide indicates that overall they are not very acutely toxic in laboratory animal studies. Indoxacarb also did not cause teratogenic, reproductive or carcinogenic effects. Although data from chronic and developmental toxicity studies on indoxacarb showed that this chemical has the potential to cause some toxicity, the expected exposure from the labeled uses of AvauntĘ Insecticide should not pose a significant risk to workers or the general public.
ECOLOGICAL EFFECTS RISK ASSESSMENT: Exposure modeling utilizing highly conservative screening assumptions predicts that several aquatic and terrestrial toxicity thresholds may be exceeded at the highest labeled application rate and shortest re-treatment intervals. The No Observable Effect Concentration (NOEC) threshold was exceeded for three marine/estuarine species at the highest predicted runoff rates. In no case, however, was a Maximum Allowable Toxicant Concentration (MATC) exceeded.
A mammalian chronic feeding Lowest Observable Effect Concentration (LOEC) Ms. was exceeded at the highest predicted vegetation residue level. Residue levels under field conditions will be lower as no foliar precipitation wash-off or dilution due to growth was factored into the screening modeling. Furthermore, the most sensitive reported end points are used for the Department's risk assessments. In this case the threshold exceeded was for hemolytic effects, specifically anemia. While these effects would reduce an individual animal's fitness should they feed exclusively on treated vegetation, lethal or reproductive effect thresholds are not reached and population level effects are unlikely.
While individual organisms may occasionally be adversely affected, AvauntĘ Insecticide, when used as labeled, is not likely to significantly impact fish or wildlife resources on a widespread or population basis.
ENVIRONMENTAL FATE RISK ASSESSMENT: The available environmental fate and expression data indicate that indoxacarb and its degradate IN-JT333 are not likely to be persistent or mobile in the environment. However, the USEPA was concerned about other degradates identified in the environmental fate studies and the complexity of their degradation process. The FIFRA Sec. 3(c)(7)(C) conditional registration of AvauntĘ Insecticide identified certain data gaps in the environmental fate data base for indoxacarb.
In the comment letter, dated October 30, 2000, accompanying the conditional registration of AvauntĘ Insecticide, the USEPA specified the following data requirements for additional elucidation of the degradates:
- photodegradation in water
- aerobic soil metabolism
- anaerobic aquatic metabolism
- aerobic aquatic metabolism
- terrestrial field dissipation
- accumulation in fish
This information is critical in order to conduct a comprehensive assessment of the leachability of indoxacarb. The potential for certain degradates to adversely impact groundwater/drinking water resources in New York State cannot be discounted. Of particular concern are groundwater resources on Long Island, where sandy soils and shallow depth to groundwater are common.
DISCUSSION: The Department's concern regarding the potential for AvauntĘ to adversely impact groundwater resources in vulnerable agricultural areas in New York State was discussed with representatives of DuPont in a telephone conference on February 22, 2002. In order to accommodate the concerns regarding the uncertainties associated with the degradate(s) leaching potential, DuPont proposed the following action items: 1) To sticker the front panel of existing stock of AvauntĘ with the text, "Not for use or sale in Suffolk and Nassau Counties, Long Island, New York."; and 2) Product produced after April 15, 2002 would bear the following text under the General Information section of the labeling: "Not for use or sale in Suffolk and Nassau Counties, Long Island, New York."
On February 27, 2002, DuPont submitted a copy of the notification to the USEPA, dated February 27, 2002, regarding this labeling change together with "stickered" labeling (SL-715 103000a 10-30-00) and proposed revised labeling (SL-820-1 022602 01-11-02) for the Department's review.
CONCLUSION: The Department hereby accepts DuPontTM AvauntĘ Insecticide (EPA Reg. No. 352-597) for registration in New York State. Enclosed for your files are the Certificate of Pesticide Registration and New York State stamped "ACCEPTED" labeling (existing stock "stickered" labeling (SL-715 103000a 10-30-00) and revised labeling (SL-820-1 022602 01-11-02).
Please note that a proposal by DuPont, or any other registrant, to register a product containing indoxacarb, whose labeled uses are likely to increase the potential for significant exposure to humans or impact to the environment, would constitute a major change in labeled (MCL) use pattern. Such an application must be accompanied by a new application fee and meet the requirements listed in Appendix 1.B. of "New York State Pesticide Product Registration Procedures" (August 1996). A proposal to remove the Long Island prohibition would likewise be processed as a MCL. Such a proposal must be accompanied by the USEPA reviews of the environmental fate data specified as a requirement of the conditional federal registration issued on October 30, 2000. These data requirements were further defined in a meeting between DuPont and USEPA's Environmental Fate and Effects Division (EFED) on September 5, 2001 and subsequent comments (via electronic mail) by EFED on October 26, 2001.
Please contact Samuel Jackling, Chief of our Pesticide Product Registration Section, at (518) 402-8768, if you have any questions.
Maureen P. Serafini
Bureau of Pesticides Management Enclosures
cc: w/enc. - N. Kim/D. Luttinger, NYS Dept. of Health
R. Zimmerman/R. Mungari, NYS Dept. of Ag. & Markets
G. Good/W. Smith, Cornell University, PMEP