EPA Registration Division contact: Andrew Ertman; 703-308-9367

Interregional Research Project No. 4

PP No. 2E7982

EPA has received a pesticide petition (2E7982) from Interregional Research Project No. 4 (IR-4) IR-4 Project Headquart ers, Rutgers, The State Un iversity of NJ, 500 College Road, east, Suite 201 W, Princeton, NJ 08540 in cooperation with Valent U.S.A. Corporation, 1600 Riviera Avenue, Suite 200, Walnut Creek, CA 94596, 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, by es tablishing tolerances for residues of the herbicide chemical flumioxazin, 2-[7-f luoro-3,4-dihydro-3-oxo- 4-(2-propynyl)-2H-1,4- benzoxazin-6-yl]-4,5,6,7-tetrahydro-1H-isoi ndole-1,3(2H)-dione: in or on the raw agricultural commodities in Artichoke at 0.02 parts per million (ppm); Cabbage and Chinese Cabbage (tight-headed varieties only ) at 0.02 ppm; Olives and olive oil at 0.02 ppm; pomegranate at 0.02 ppm; cactus fru it at 0.1 ppm, and cactus pads at 0.05 ppm. EPA has determined that the petition contains data or information regarding the elements

set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this tim e or whether the data supports granting of the petition. Additional data may be need ed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism . The metabolism of flumioxazin is adequately understood for the purpose of granting the proposed tolerances.

2. Analytical method. Practical analytical methods for detecting and measuring levels of flumioxazin have been developed an d validated in/on all appropriate agricultural commodities and respective processing fractions. The LOQ of flumioxazin in the methods is 0.02 ppm which will allow monitori ng of food with residues at the levels proposed for the tolerances.

3. Magnitude of residues . Residue data has been submitted which adequately support the requested tolerances.

B. Toxicological Profile

The toxicological profile for flumiox azin, which supports this petition for tolerances was published in the Federal Re gister on March 31, 2004 (69 FR 16823)(FRL7351-2). Immunotoxicity and neurotoxicity studies have been submitted to the Agency to fulfill revised FIFRA 40 CFR part 158.340 data requirements. The results of these studies show no indication of immunotoxicity or neurotoxicity and do not result in any changes to the toxicology endpoints us ed for risk assessment purposes.C. Aggregate Exposure

1. Dietary exposure

. A Tier 1 dietary (food and wate r) exposure assessment was conducted to evaluate the potential risk due to acute and chronic dietary exposure of the U.S. population and various subpopulations to residues of flumioxazin. Residues from

use of Flumioxazin on the curr ently proposed minor use crops were not included in the current assessment because the overall aggr egate exposure contribution is considered negligible. These minor use residues w ill be included in the aggregate exposure

assessment at a later date.

i. Food . Dietary exposures were calcul ated using DEEM-FCID version 2.16. Key assumptions for the Tier 1 assessment are tolerance-level residues on all commodities, 100% crop treated and default processing factors for processed commodities without processing data.

ii. Drinking water

. The current assessment also includes potential residues from aquatic uses of flumioxazin to cons ervatively estimate potential exposures from drinking water. For the acut e assessment, the major source of flumioxazin exposure to drinking wate r was assumed to be the maximum labeled treatment rate of 400 ppb for tr eated water bodies. For the chronic assessment, the drinking water concen tration of flumioxazin and its major hydrolysis degradates was assumed to be 142 ppb based on the 30-day average concentration for the aquatic use.

2. Non-dietary exposure

. Non-dietary (residential) aggregate exposures to Flumioxazin may occur because people may swim in flumioxazin-treated water bodies. Short-term aggregate exposure scenarios were constructed by combining chronic dietary exposures with those estimated for adults or children swimming in treated water bodies.

D. Cumulative Effects

Section 408(b)(2)(D)(v) requires that the Agency must consider "available information" concerning the cumulative effects of a pa rticular pesticide's residues and "other

substances that have a common mechanism of toxicity." Available information in this context includes not only toxicity, chemistr y, and exposure data, but also scientific policies and methodologies for understandin g common mechanisms of toxicity and conducting cumulative risk assessments. EPA doe s not have, at this time, available data

to determine whether flumioxazin has a co mmon mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. For the purposes of this tolerance ac tion, EPA has not assumed that flumioxazin has a common mechanism of toxicity with other substances.

E. Safety Determination

1. U.S. population

. i. Acute Risk. The acute dietary exposure estimate to flumioxazin residues in

food and water at the 95th th percentile for females 13-49 years old wascalculated to be, at most, 67.4% of the acute Population Adjusted Dose (aPAD). This is the only population subgr oup with an identifi ed acute toxicity endpoint. Residues from water are the pr imary contributor to the exposure. The aPAD was defined using the NOEL fr om an oral developmental study in rats and includes an uncertainty factorof 100 to account for intra- and interspecies variation (aPAD = 0.03 mg/kg/ day). Aggregate exposures below 100% of the aPAD are generally considered to represent a re asonable certainty of no harm to exposed populations.

ii. Chronic Risk. The potential chronic e xposure from food and water to the U.S. Population and various non-child/infant population subgroups will utilize at

most 19.1% of the cPAD. Residues from water are the primary contributor to the exposure. The cPAD was defined using the NOEL from a rat two-year chronic/oncogenicity study and includes an uncertainty factor of 100 to account for intra- and inter-species variation (cPAD = 0.02 mg/kg/day). Aggregate exposures below 100% of th e aPAD are generally considered to represent a reasonable ce rtainty of no harm to exposed populations.

2. Infants and children . Safety Factor for Infants and Children. FFDCA section 408 provides that EPA shall apply an additional margin of safety, up to ten-fold, for added protection for infants and childre n in the case of threshold effects unless EPA determines that a different margin of safety will be safe for infants and children. EPA has determined that the special 10x SF to protec t infants and children should be removed [Federal Register of March 31, 2004 (69 FR 16823) (FRL-7351-2)]. The FQPA factor has been removed because developmenta l toxicity and offspring toxicity

NOAELs/LOAELs are well characte rized; there is a well-defined dose-response curve for the cardiovascular effects; a nd the endpoints of concern used for overall risk assessments are appropriate for the route of exposure and population subgroups.

i. Acute Risk. No acute endpoint has b een identified for infants and children. Therefore, no assessment of acute expos ure from food or water to this subgroup is required. ii Chronic Risk. The potential chronic di etary exposure from food and water to children 1-2 years old (the most highl y exposed child/infant subgroup) will

utilize at most 54% of the cPAD. Aggregate exposures below 100% of the cPAD are generally considered to repres ent a reasonable certainty of no harm to exposed populations. Aggregation of dietary exposures with residential exposures (e.g. swimming) in treated bodies of water also result s in acceptable risks. MOEs for the various aggregat e exposure scenarios range from 450 to 620. MOEs greater than 100 indicate a reasonable certainty of no harm resulting from the associated exposures.

F. International Tolerances Flumioxazin has not been evaluated by the JMPR and there are no Codex Maximum Residue Limits (MRL) for flumioxazin.