Mefluidide Use Closure Memo
EPA-HQ-OPP-2007-0431-0003

• The risk assessments for mefluidide will be based on the use sites and usage date in BEAD’s LUIS report, documents presented by the registrants, and the product labels.
• The two registrants for mefluidide, PBI/Gordon (technical registrant) and The Scotts Company (end-use registrant) are supporting all of the uses for reregistration on their respective labels.
• The uses that will be included in the reregistration assessment are; agricultural/farm structures/buildings and equipment, agricultural/nonagricultural uncultivated areas/soils, airports/landing fields, commercial industrial lawns, commercial institutional/industrial premises/equipment (indoor/outdoor), golf course turf, hospitals/medical institutions premises (human veterinary), household domestic dwellings outdoor premises, industrial areas (outdoor), nonagricultural outdoor buildings/structures, nonagricultural rights-of-way/fencerows/hedgerows, ornamental and or shade trees, ornamental ground cover, ornamental herbaceous plants, ornamental lawns and turf, ornamental nonflowering plants, ornamental woody shrubs and vines, paths/patios, paved area (private roads/sidewalks), recreational areas, and residential lawns.

Table A3. Non-Food/Non-Feed Use Patterns Summary for Mefluidide (Case 2370)
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TABLE A3. NON-FOOD/NON-FEED USE PATTERNS SUMMARY FOR Mefluidide, diethanolamine salt (CASE 2370)
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TABLE A3. NON-FOOD/NON-FEED USE PATTERNS SUMMARY FOR Potassium mefluidide (CASE 2370)
EPA-HQ-OPP-2007-0431-0006

TABLE A3. NON-FOOD/NON-FEED USE PATTERNS SUMMARY FOR Mefluidide, diethanolamine salt (CASE 2370)
EPA-HQ-OPP-2007-0431-0007

Mefluidide; Diethanolamine Mefluidide, and Potassium Mefluidide- Phase 2, (30-Day Error only Correction), HED Chapter of the Re-registration Eligibility Decision Document (RED).
EPA-HQ-OPP-2007-0431-0008

• There are no agricultural or any food related pesticide uses of mefluidide. Therefore, no dietary exposure from food is expected. However, there is potential for drinking water exposure due to the outdoor uses of mefluidide.
• Based on the structural similarities of mefluidide and its diethanolamine (DEA) and potassium salts, where they all share the same anion- anilide, and the physical and chemical properties of the DEA and potassium salts, where they dissociate 100% back to free mefluidide in aqueous environments, the risk assessment team concluded that mefluidide DEA and potassium salts are biologically equivalent to mefluidide and thus they share the same toxicity as the free mefluidide. Therefore, it is reasonable to bridge mefluidide toxicity data to mefluidide salts and vice versa.

• Subchronic and chronic toxicity of mefluidide is manifested by decreased body weight and body weight gain in several species tested (rats, rabbits and dogs). Dogs appeared to be most sensitive species with the critical toxicological effects of cortical nephrosis and body weight loss. In rats and rabbits, critical effects observed were tremors, hunched posture, salivation, reduced body weight and body weight gain.

• Mefluidide and its diethanolamine salt subchronic and chronic toxicity are manifested by decreased body weight and body weight gain in several species tested (rats, rabbits and dogs). Dogs are most sensitive to these effects, which occur at doses as low as 15 mg/kg/day in diets fed for one year. In addition, dogs fed with mefluidide for one year exhibited chronic cortical nephrosis at doses of 150 mg/kg/day. Increased incidence of liver hyperplastic nodules in both sexes was observed in mice fed with mefluidide at doses of 270 mg/kg/day and higher.

• Mefluidide or its DEA salt has not been tested for subacute or subchronic inhalation toxicity. However, both of them are in category IV for acute inhalation toxicity.

• This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These studies (listed in Appendix B) have been determined to require a review of their ethical conduct, and have received that review.

• Developmental effects of Mefluidide in rats included increased number of early resorptions and mean postimplantation loss. These effects were observed at the same dose that caused maternal toxicity indicating there was no increased susceptibility to fetuses. The maternal toxicity included tremors, decreased body weight, weight gain and mortality. In rabbit, the LOAEL/NOAEL for developmental toxicity were above the highest dose tested (60 mg/kg/day). In the 3-generation reproduction toxicity study in rats, the offspring toxicity was characterized by decreased body weights in both sexes and both litters in all generations.

• After adjusting to the pure active ingredient, the maternal NOAEL is 58 mg/kg/day and the LOAEL is 115 mg/kg/day based on clinical signs (tremors, dark material around the nose, urine stain and reddish vaginal discharge), decreased body weight gain, decreased food consumption and mortality (2/25 females). The developmental toxicity NOAEL is also 58 mg/kg/day, the LOAEL is 115 mg/kg/day based on increase in the number of early resorptions and increase in mean postimplantation loss.

• . Evidence of Neurotoxicity. Acute and subchronic neurotoxicity studies were not performed. Clinical signs of neurotoxicity (such as tremors, ataxia, atonia, decreased limb tone, salivation) were seen in several studies (14-day oral in rabbit at or above 200 mg/kg/day, demyelination study in chickens at 1000 mg/kg/day and two developmental toxicity studies in rats at 115 mg/kg/day. Edema and swelling with myelin loss in sciatic nerve was observed in a dermal toxicity study in rabbits at doses of 720 mg/kg and above. However, these effects were not seen in an additional dermal test of similar duration using a 58.2% mefluidide formulation or diethanolamine salt of mefluidide 28.8%.

• Environmental Degradation. The only identified degradation product was 5-amino-2, 4-dimethyltrifluoromethanesulfonilide. It was found at a maximum daily concentration of 2.8% of applied dose (MRID 43162201, aerobic soil). The risk assessment team concluded that this degradate is not of concern based on its structure (structurally similar to the parent, there fore it is not likely to be significantly more toxic than the parent), and the fact that it is a minor degradate (<10% of the applied dose). The residue of concern for drinking water assessment is parent only.

• . The following acceptable studies are available:
- Developmental toxicity studies in rats
- Developmental toxicity studies in rabbits
- Two-generation reproduction study in rats

Mefluidide - Toxicology section for the Reregistration Eligibility Decision Document (RED) (January 31, 2007)
EPA-HQ-OPP-2007-0431-0009

Mefluidide – Occupational and Residential Exposure and Risk Assessment for the Reregistration Eligibility Decision (RED)
EPA-HQ-OPP-2007-0431-0010

Appendix A 1-3 Standard Formulas Used for Calculating Occupational and Residential Exposures to Mefluidide; Ocupational Handler Exposure Data and;Risk Calculations for Mefluidide; Residential Handler
EPA-HQ-OPP-2007-0431-0011

Appendix B – Mefluidide Occupational Handler Risks
EPA-HQ-OPP-2007-0431-0012

Appendix C – Residential Handler Risks
EPA-HQ-OPP-2007-0431-0013

Appendix D – Residential Turf Post Application Risk Assessment for Melfuidide
EPA-HQ-OPP-2007-0431-0014