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 Headquarters, Rutgers, The State University 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 establishing tolerances for residues of the 

herbicide chemical flumioxazin, 2-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-

benzoxazin-6-yl]-4,5,6,7-tetrahydro-1H-isoindole-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 fruit 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 time or whether the data supports granting of the 

petition. Additional data may be needed 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 and 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 monitoring 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 flumioxazin, which supports this petition for 

tolerances was published in the Federal Register 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 used for risk assessment purposes. 
C. Aggregate Exposure

1. Dietary exposure. A Tier 1 dietary (food and water) 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 currently proposed minor use crops were not included in the 

current assessment because the overall aggregate exposure contribution is considered 

negligible. These minor use residues will be included in the aggregate exposure 

assessment at a later date. 

i. Food. Dietary exposures were calculated 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 conservatively estimate potential exposures 

from drinking water. For the acute assessment, the major source of 

flumioxazin exposure to drinking water was assumed to be the maximum 

labeled treatment rate of 400 ppb for treated water bodies. For the chronic 

assessment, the drinking water concentration 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 particular pesticide's residues and "other 

substances that have a common mechanism of toxicity." Available information in this 

context includes not only toxicity, chemistry, and exposure data, but also scientific 

policies and methodologies for understanding common mechanisms of toxicity and 

conducting cumulative risk assessments. EPA does not have, at this time, available data 

to determine whether flumioxazin has a common mechanism of toxicity with other 

substances or how to include this pesticide in a cumulative risk assessment. For the 

purposes of this tolerance action, 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 95thth percentile for females 13-49 years old was 
calculated to be, at most, 67.4% of the acute Population Adjusted Dose 

(aPAD). This is the only population subgroup with an identified acute toxicity 

endpoint. Residues from water are the primary contributor to the exposure. 

The aPAD was defined using the NOEL from an oral developmental study in 

rats and includes an uncertainty factor of 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 reasonable certainty 

of no harm to exposed populations. 

ii. Chronic Risk. The potential chronic exposure 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 the aPAD are generally considered to 

represent a reasonable certainty 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 children 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 protect 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 developmental toxicity and offspring toxicity 

NOAELs/LOAELs are well characterized; there is a well-defined dose-response curve for 

the cardiovascular effects; and 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 been identified for infants and children. 

Therefore, no assessment of acute exposure from food or water to this 

subgroup is required. 

ii Chronic Risk. The potential chronic dietary exposure from food and water to 

children 1-2 years old (the most highly exposed child/infant subgroup) will 

utilize at most 54% of the cPAD. Aggregate exposures below 100% of the 

cPAD are generally considered to represent 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 results in acceptable 

risks. MOEs for the various aggregate 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.