EPA REGISTERED DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE

PETITIONS PUBLISHED IN THE FEDERAL REGISTER.

EPA Registration Division contact: Kable Bo Davis, (703) 306-0415

Gowan Company

[Insert petition number]

EPA has received a pesticide petition ([insert petition number]) from Gowan

Company, LLC, P.O. Box 556 Yuma, AZ 85366 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.

1. by establishing a tolerance for residues of

Benzobicyclon 3-[2-Chloro-4-(methylsulfonyl)benzoyl]-4-(phenylthio) bicyclo-

[3.2.1]oct-3-en-2-one in or on the raw agricultural commodity rice, grain and rice, straw

at 0.1 parts per million. EPA has determined that the petition contains data or

information regarding the elements set forth in section 408 (d)(2) of the FDDCA;

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 nature of the residues in plants is adequately understood

for purposes of this tolerance. A metabolism study was conducted in rice plants, and a

supplemental metabolism study was conducted in rice seedlings.

2. Analytical method. A practical analytical method, LC/MS, which detects and

measures residues of benzobicyclon and 1315P-070, is available for enforcement

purposes with a limit of detection that allows monitoring of food with residues at or

above the levels set in this tolerance.

3. Magnitude of residues. Four field trials were conducted by Gowan Company in

support of the proposed regional (California) label for benzobicyclon use in/on rice. The

results of these trials support the proposed tolerance levels: rice, grain 0.1 ppm; and rice,

straw 0.1 ppm.

B. Toxicological Profile

1. Acute toxicity. A battery of acute toxicity studies places technical grade
benzobicyclon in Toxicity Category IV for acute oral LD50 (LD50 > 5000 mg/kg),

Category III for dermal LD50 (LD50 >2000 mg/kg), Category III for inhalation LC50

(LC50 >2.0 mg/L), Category IV for primary eye irritation (non irritant), and Category IV

for dermal irritation (non irritant). Benzobicyclon is a non-sensitizer. Overall, acute

toxicological studies place technical grade benzobicyclon in Toxicology Category III.

2. Genotoxicity. The following genotoxicity studies were negative: in-vitro

bacterial reverse mutation assay, in-vitro bacterial DNA repair assay, and in-vivo mouse

micronucleus assay. An in-vitro Chinese hamster ovary cell chromosomal aberration

assay gave positive results.

3. Reproductive and developmental toxicity. In a 2-generation dietary

reproduction toxicity study in rats, the parental NOAEL was ~6 (males) and at least 85

(females) mg/kg/day, based on organ weight elevations in both sexes and renal pathology

findings (hyaline droplet formation) in males. The reproductive performance was

unaffected by benzobicyclon and there were no adverse effects on growth or development

of pups at the highest dose tested (at least 1176 and 1741 mg/kg/day for males and

females, respectively). In developmental oral toxicity studies in rats and rabbits, there

was no maternal toxicity and no developmental effects at doses up to 1000 mg/kg/day

(highest dose tested).

4. Subchronic toxicity. In a 13-week oral toxicity study in dogs, the NOAEL was

2000 mg/kg/day, the highest dose tested. In a 13-week dietary toxicity study in rats, the

NOAEL was 1.1 mg/kg/day for males, and the NOEL was 25 mg/kg/day for females,

based on renal pathology (hyaline droplet formation) in males, and clinical pathology

changes and organ weight elevations in both sexes.

5. Chronic toxicity. In a 52-week oral toxicity study in dogs, the NOAEL was

1000 mg/kg/day, the highest dose tested. In a 104-week dietary toxicity/carcinogenicity

study in rats, the NOAEL was 1.7 (males) and 42 (females) mg/kg/day, based on renal

pathology (hyaline droplet formation) in males, and altered clinical pathology parameters

and organ weight elevations in females, but there was no indication of oncogenicity at the

highest dose tested of 3.4 (males) and 427 mg/kg/day (females). In a 78-week dietary

carcinogenicity study in mice, the NOEL was 373 (males) and 473 (females) mg/kg/day,

based on slightly elevated liver weights and hepatocyte hypertrophy, but there was no

indication of oncogenicity at the highest dose tested of 3817 (males) and 4807 (females)

mg/kg/day.

6. Animal metabolism. The metabolism of hexythiazox has been studied in goats

and rats.

7. Metabolite toxicology. There are no metabolites of toxicological concern based

on differential metabolism between plants and animals.

8. Endocrine disruption. No specific tests have been conducted with

benzobicyclon to determine whether the chemical may have any effect in humans that is

similar to an effect produced by a naturally occurring estrogen or other endocrine effects.
However, there were no significant findings in other relevant toxicity tests, i.e.,

developmental toxicity and multi-generational reproduction toxicity studies, which would

suggest that benzobicyclon produces effects characteristic of hormonal disruption.

C. Aggregate Exposure

1. Dietary exposure. Gowan Company conducted a dietary, drinking water and

aggregate benzobicyclon exposure-risk assessment for rice.

i. Food. Acute Exposure. No acute endpoint was identified in the

toxicological studies for benzobicyclon, therefore, a quantitative acute

dietary exposure assessment was considered not necessary.

Chronic Exposure. A chronic risk assessment by Gowan Company using

DEEM-FCID and the NHANES 2003-2008 food consumption survey

indicates that the proposed use results in a dietary risk of 1.3% of the

RfD for the general US population and 4.4% of the RfD for the most

highly exposed subpopulation, non-nursing infants.

ii. Drinking Water. A commodity distribution analysis conducted by

Gowan Company showed that direct and indirect exposures from water

from all sources occupied 4.1% of the RfD.

2. Non-dietary exposure. Gowan Company has conducted occupational and

bystander exposure-risk assessments for benzobicyclon to be used on rice. Gowan

Company believes there should be no concern for occupational handlers (mixer/loader or

aerial applicator), post-applicators (scouts), or residential bystanders as it relates to the

unintentional potential exposure to benzobicyclon dermally or inhalationally.

D. Cumulative Effects

Gowan Company does not believe that benzobicyclon shares a common mechanism of

toxicity with other substances.

E. Safety Determination

1. U.S. population. Acute risk. No adverse effect resulting from a single oral

exposure to benzobicyclon has been identified, thus benzobicyclon is not expected to

pose an acute risk.

Chronic risk. Gowan Company has determined that the chronic exposure to

benzobicyclon from food and water will utilize no more than 4.4% of the cPAD for the

population group receiving the greatest exposure (non-nursing infants). This conservative

assessment utilized a maximum residue level of 0.1 ppm, 100% crop treatment, an

estimated benzobicyclon water concentration of 0.02 ppm using Tier I Rice Model, and a

combined uncertainty/FQPA factor of 100.

2. Infants and children. Based on these risk assessments, it can be concluded that

there is a reasonable certainty that no harm will result to the general population, or to

infants and children from aggregate exposure to benzobicyclon residues.
F. International Tolerances

No national or transnational maximum residue levels for benzobicyclon exist apart from

those established in Korea and Japan.