|New York State Department of Environmental
Division of Solid & Hazardous Materials
Bureau of Pesticides Management
Pesticide Product Registration Section
50 Wolf Road, Albany, New York 12233-7257
Phone: (518) 457-7446 FAX: (518) 485-8990
|March 29, 2001|
RETURN RECEIPT REQUESTED
Laura L. Whatley, Ph.D.
State Registration Specialist
P.O. Box 13528
Research Triangle Park, NC 27709-3528
Dear Dr. Whatley:
Re: Registration of the New Active Ingredient Mepiquat Chloride Contained in the Product Ponnax® Plant Regulator (EPA Reg. No. 7969-98)
The New York State Department of Environmental Conservation ("The Department") has completed review of your application (received 06/30/00) and supplemental information supplied to date regarding registration of the referenced pesticide product in New York State. The subject application and data package were deemed complete for purposes of technical review on November 2, 2000 following one determination of incompleteness. Pursuant to the review time frame specified in Environmental Conservation Law (ECL) §33-0704.2, a registration decision date of April 1, 2001 was established.
Ponnax® Plant Regulator (EPA Reg. No. 7969-98), containing 23.6% mepiquat chloride, is a foliar-applied plant growth regulator for use on Concord and Niagara grapes only. The maximum seasonal Ponnax® use rate (one pint) is equivalent to 0.25 pounds mepiquat chloride/acre/season.
The Department conducted toxicological, ecological effects and environmental fate risk assessments for mepiquat chloride and the Ponnax® formulation.
TOXICOLOGICAL RISK ASSESSMENT:
Neither the active ingredient nor the formulated product was very toxic in acute oral, dermal or inhalation exposure studies in laboratory animals, nor were they dermal sensitizers (tested on guinea pigs) or very irritating to the skin (tested on rabbits). On the other hand, whereas the active ingredient was not very irritating to rabbit eyes, the formulated product caused some eye irritation.
Mepiquat chloride caused some toxicity in chronic animal feeding studies. In a one-year dog feeding study, impaired neurological function (slight sedation, spasms and salivation) and kidney effects (epithelial vacuolization of renal distal tubules) were reported at a dose level of 170 milligrams per kilogram body weight per day (mg/kg/day); the no-observed-effect level (NOEL) was 58.4 mg/kg/day. In a chronic feeding/oncogenicity study in rats, mepiquat chloride caused decreased body weight and body weight gains, some kidney effects in males (increase in urinary crystals) and adrenal effects in females (pathological changes in the adrenal cortex) at 268 mg/kg/day; the NOEL was 106 mg/kg/day. In a chronic feeding/oncogenicity study in mice, no treatment-related effects were observed at the highest doses of mepiquat chloride tested (1,140 mg/kg/day for males and 1,348 mg/kg/day for females). The United States Environmental Protection Agency (USEPA) Hazard Identification Assessment Review Committee (HIARC) established a reference dose (RfD) of 0.6 mg/kg/day for mepiquat chloride based on the NOEL from the one-year dog study (58.4 mg/kg/day) and an uncertainty factor of 100. This RfD has not yet been adopted by the USEPA’s Integrated Risk Information System (IRIS) which lists the RfD for this chemical as 0.03 mg/kg/day based on a NOEL (25 mg/kg/day) from a 90-day dog feeding study and an uncertainty factor of 1,000. This RfD was placed in the USEPA’s IRIS in August 1988 and is based on a subchronic study. By contrast, the RfD for mepiquat chloride established by USEPA’s HIARC is based on a more recently completed chronic study. Generally, chronic studies are preferable to subchronic studies for establishing RfD values.
Mepiquat chloride caused some developmental toxicity in the offspring of pregnant rabbits, but not pregnant rats fed this chemical during organogenesis at doses that also caused maternal toxicity. In rabbits, increased incidence of skeletal variations and maternal toxicity (reduced body weight gain and food consumption) occurred at 150 mg/kg/day; the NOEL for both skeletal variations in offspring and maternal toxicity was 100 mg/kg/day. In rats, maternal toxicity (tremors, ataxia, hypersensitivity) was noted at 300 mg/kg/day; the NOEL was 150 mg/kg/day. No developmental effects were noted at doses up to 300 mg/kg/day; the highest dose tested. In a two-generation reproduction study in rats, mepiquat chloride did not cause reproductive effects even at the highest doses tested which were about 575 mg/kg/day for males and 627 mg/kg/day for females. Parental toxicity was observed, however, at these doses which consisted of neurological impairment and decrease in body weights and body weight gain; the respective NOELs for males and females were about 153 and 164 mg/kg/day.
Mepiquat chloride did not cause oncogenic effects in either rat or mouse chronic feeding studies. It also was negative in a number of genotoxicity tests. The USEPA classified mepiquat chloride as a "not likely" human carcinogen.
The USEPA established tolerances for mepiquat chloride residues in or on grapes at 1.0 part per million (ppm). The USEPA estimated that chronic dietary exposure to these residues would be less than 0.3 percent of the chronic population adjusted dose (cPAD) of 0.6 mg/kg/day for the most highly exposed subpopulation, children one to six years old. This chronic exposure analysis is based on the assumption that 100 percent of crops are treated and contain tolerance level residues.
The USEPA conducted an exposure risk assessment for dermal and inhalation exposure of workers to mepiquat chloride based on its labeled use in the Ponnax® product. For mixer/loader/applicators, a margin of exposure (MOE) was estimated to be about 3,500 for combined dermal and inhalation exposures. This estimate assumes that workers wore long-sleeved shirt, long pants and gloves (other than shoes and socks) which are required by the label. The dermal and inhalation absorption factors used in this risk assessment were 25 and 100 percent, respectively. The NOEL used for estimating this MOE from dermal and inhalation exposure was 58.4 mg/kg/day, which is from a one-year dog feeding study. This evaluation was conducted for short-term exposure due to the label requirement that Ponnax® can only be applied once per year. The USEPA also conducted an assessment for workers involved in post-application activities (e.g., harvesting, pruning) on treated grapes using the NOEL of 58.4 mg/kg/day from the one-year dog feeding study. For workers handling grape vines immediately after application, an MOE of 240 was calculated. An MOE of 510 was calculated for workers contacting treated grapes 7 days after treatment. The Ponnax® label contains a 12-hour restricted entry interval requirement. Generally, the USEPA considers MOEs of 100-fold or greater to provide adequate protection for workers.
There are no chemical-specific federal or State drinking water/groundwater standards for mepiquat chloride. Based on its chemical structure, mepiquat chloride falls under the 50 microgram per liter (&g/L) New York State drinking water standard for "unspecified organic contaminants" (10 NYCRR Part 5, Public Water Systems).
The available information on mepiquat chloride and the formulated product Ponnax® indicates that they are not very acutely toxic in laboratory animal studies. Although data from chronic studies on mepiquat chloride showed that this chemical has the potential to cause certain neurological and other effects, the expected exposure to mepiquat chloride from using the Ponnax® product should not pose a significant risk to the general public or to workers.
ECOLOGICAL EFFECTS RISK ASSESSMENT:
Ponnax® is applied to Niagara and Concord grapes primarily to increase berry set, thus improving yield. The active ingredient, mepiquat chloride, is a quaternary ammonium compound. It functions by inhibiting the production of the plant growth hormone gibberellic acid, reducing internode length, hastening maturity, and retarding abscission. It was originally registered for use on cotton in the mid-1980s.
Mepiquat chloride is cationic and binds strongly to clay minerals in soil. It is stable to photolysis and hydrolysis, but is degraded rapidly to CO2 by aerobic microorganisms. No data on the fate of mepiquat chloride in water was provided, however, quaternary ammonium compounds in general tend to behave in the same manner in water, i.e., they bind strongly to sediment and degrade rapidly under aerobic conditions. The average half-life of mepiquat chloride in soil due to microbial degradation was 7.9 days and the average half-life in field dissipation studies was 23.8 days. Mepiquat chloride degraded completely to CO2, with no metabolite ever constituting more than 5% of the applied active parent compound.
Potential ecological impacts were modeled using the MAMTOX, AVTOX and AQUALIFE models. Model results indicated that no mammalian, avian, or aquatic toxicity thresholds were exceeded. The use of Ponnax®, as labeled, should not present any significant risks to exposed non-target organisms.
ENVIRONMENTAL FATE RISK ASSESSMENT:
Of the five Data Evaluation Record (DER) reports submitted by BASF only one was found to be acceptable and two were found to be supplemental by the USEPA. The USEPA published a Reregistration Eligibility Document (RED) in 1997 for mepiquat chloride which provided additional information. The following environmental fate assessment of mepiquat chloride is taken from the RED:
Although acceptable DERs for all studies were not available, utilizing the information provided in the RED and the results of the LEACHM modeling, it appears that Ponnax® will not impact groundwater when used as labeled.
When used as labeled, Ponnax® should not cause unreasonable adverse effects to humans or the environment. The Department hereby accepts Ponnax® Plant Regulator (EPA Reg. No. 7969-98) for registration in New York State. Enclosed for your files are the Certificate of Pesticide Registration and New York State stamped-"ACCEPTED" labeling.
Please note that a proposal by BASF Corporation or any other registrant to register a product containing mepiquat chloride, whose labeled uses are likely to increase the potential for significant impact to humans, property or 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).
Please contact Frank Hegener, Chief of our Pesticide Product Registration Section, at (518) 457-7446, if you have any questions.
Maureen P. Serafini
Bureau of Pesticides Management
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 PMEP
bcc: w/enc. - T. Sinnott/T. Martin, DFW&MR
PCS III, Reg. 1
PCS II’s, Regions 2-7 &9
D. Rollins, Region 8
M. Radzevich (2)
BASF Corporation File
Active Ing. File
bcc: w/o enc. - S. Sanford, DFW&MR
J. Leach/J. Kaplan, NYS DOH