At 1045/1248 mg/kg/day:  decreased survival in males, decreased body weight in females, increased abs/rel liver weight, chronic progressive glomerulonephropathy, tissue mineralization.

no evidence of carcinogenicity
870.4300

Carcinogenicity
(mouse)
44617729 (1998)
Acceptable/guideline
0, 70, 2800, 7000 ppm
M:  0, 10.0, 40.5 or 1020 mg/kg/day
F:  0, 12.8, 529 or 1354 mg/kg/day

NOAEL =  1020/1354 mg/kg/day [M/F]
LOAEL >1020/1354 mg/kg/day [M/F](HDT)

no evidence of carcinogenicity
Gene Mutation
870. 5100
Bacterial reverse gene mutation - Salmonella
44144428 (1995)
Acceptable/guideline
0, 50, 200, 500, 2000, 5000 ug/plate, initial assay; 0, 160, 300, 500, 900, 1600 ug/plate, repeat assay
No evidence of mutagenicity with or without S9 activation up to solubility limit (precipitation observed at >=900 ug/plate).
Gene Mutation
870.5100
Bacterial reverse gene mutation  - Salmonella
44617733 (1998)
Acceptable/guideline
0, 50, 200, 500, 2000, 5000 ug/plate, test material:  RH-117,236 (Metabolite M-B)
No evidence of mutagenicity with or without S9 activation up to solubility limit (precipitation observed at 2000 and 5000 ug/plate)
In Vitro Mammalian Gene Mutation
870.5300
HGPRT forward gene mutation assay (Chinese hamster ovary, or CHO, cells)
44617734 (1994)
Acceptable/guideline
0, 0.1, 0.5, 1.0, 5.0, 10, 50, 100, 500, 1000, 1250 ug/mL (range-finding study);
0.5, 1.0, 5.0, 10, 50, 100 ug/mL (definitive study)
No evidence of mutagenicity with or without S9 activation up to solubility limit (precipitation observed at >=100 ug/mL).
In Vitro Cytogenetics
870.5375
Chromosomal aberration, CHO cells
44617735 (1994)
Acceptable/guideline
0, 0.21, 0.63, 2.1, 6.3, 21, 63, 108, 625, 1250 ug/mL (range-finding study);
0, 13, 125, 100, 150 ug/mL (definitive study)
No evidence of increased frequency of chromosomal aberration in the presence or absence of S9 activation up doses causing reduced mitotic indices (>=50 ug/mL).
Other Effects
870.5395
In vivo mouse micronucleus assay
44617801 (1995)
Acceptable/nonguideline
0, 500, 2500, 5000 mg/kg single IP dose
No evidence of increased frequency of micronucleus formation in treated CD-1mice in bone marrow at 24 or 48 hrs postdosing; tested up to the limit dose for this assay.
870.6200a

Acute neurotoxicity screening battery (rat)
44617802 (1996)
Acceptable/guideline
0, 1000, 2000 mg/kg by gavage
NOAEL = 1000 mg/kg (males); 2000 mg/kg (females; HDT)
LOAEL = 2000 mg/kg (males) based on decreased hindlimb grip strength on Day 0; >2000 mg/kg females (HDT)
870.6200b

Subchronic neurotoxicity screening battery (rat)
44617803 (1996)
Acceptable/guideline
0, 200, 2000 or 20,000 ppm in diet
Males 0, 13, 130, 1318 mg/kg/day
Females 0, 16, 159, 1577 mg/kg/day
NOAEL = 1318/1577 mg/kg/day [M/F]; LOAEL > 1318/1577 mg/kg/day [M/F] (HDT)
870.7485

Metabolism and pharmacokinetics
(rat)
44617804 (1998)
Acceptable/guideline
Single gavage doses of 10 mg/kg and 1000 mg/kg; 5-day repeated gavage doses of 10 mg/kg
Absorption and excretion were rapid (<48 hrs postdosing).  Tissue distribution was extensive but bioaccumulation was not observed.  Major route of excretion was via feces (86-97%) and to a lesser extent, the urine (5-13%).  Enterohepatic circulation was observed.  The primary routes of metabolism were O-demethylation and oxidative hydroxylation followed by conjugation with glucuronic acid.
870.7600
Dermal penetration (rat)
44638202 (1998)
Acceptable/guideline

Mean dermal absorption at 10 and 24 hrs was 2% using an 80WP formulation.
870.7800
Immunotoxicity (female rat)
48592601 (2011)
Acceptable/guideline
0, 76.9, 324 or 1076 mg/kg/day in the diet (ppm not indicated)
Immunotoxicity NOAEL = 1076 mg/kg/day
Immunotoxicity LOAEL = not established
Systemic toxicity NOAEL = = 76.9 mg/kg/day
Systemic toxicity LOAEL = 324 mg/kg/day, based on increased liver weights.

A.3	Hazard Identification and Endpoint Selection

A.3.1	Acute Reference Dose (aRfD)  -  All Populations including Infants and Children and Females age 13-49

An acute reference dose for methoxyfenozide was not selected.  An appropriate toxicity dose and endpoint were not identified that could be attributed to a single exposure.  Decreased hindlimb grip strength in male rats in the acute neurotoxicity study was only observed at the limit dose of 2000 mg/kg on the day of dosing.

A.3.2	Chronic Reference Dose (cRfD)

Study Selected: Chronic Feeding-Rat and Dog (co-critical studies)
MRID Nos.:  44617731 (rat) and 44617728 (dog)
Executive Summaries:  See Appendix A, Guideline [§ 870.3150 (dog study) and 870.3500 (rat study)]
Dose and Endpoint for Risk Assessment: NOAEL = 10.2 mg/kg/day (rat study), based on hematological changes (decreased RBC counts, hemoglobin concentrations, and/or hematocrit in males and females), liver effects (increased liver weights in males; periportal hepatocellular hypertrophy in males and females), histopathological changes in the thyroid (increased follicular cell hypertrophy, altered colloid in males) and possible adrenal toxicity (increased adrenal weights in males and females) seen at the LOAEL = 411 mg/kg/day.  Supported by the co-critical chronic dog NOAEL = 9.8 mg/kg/day, based on mild hematological changes (decreased RBC counts, hemoglobin concentrations and/or hematocrit in males and females; slight methemoglobinemia in males and females; increased platelets in males) and clinical chemistry changes (increased total serum bilirubin in males and females; slightly increased severity of bilirubinemia in males) seen at the LOAEL = 106 mg/kg/day.
Comments about Study/Endpoint/Uncertainty Factors:  These studies were selected because they were of the appropriate duration (chronic) and route of exposure (dietary) and provided the most sensitive doses and endpoints.  They were selected as co-critical because of their similar NOAELs, both of which provide a cRfD of 0.10 mg/kg/day.  The selected dose is protective of potential hematological, hepatic and thyroid effects identified in two-week dietary studies in the rat and dog, which identified slightly higher NOAELs (see A.3.5, below), as well as potential developmental effects.  A combined UF of 100x was utilized (10X each to account for inter- and intra-species variability).

A.3.3	Incidental Oral Exposure (Short- and Intermediate-Term)

An incidental oral exposure dose and endpoint were not selected.  Methoxyfenozide may be used on ornamental plants in a residential setting.  However, post-application incidental oral exposure is not expected since the extent to which young children engage in prolonged play or other activities involving such areas is low, and this assessment was not performed.

A.3.4	Dermal Exposure (Short- and Intermediate-Term)

A dose and endpoint for dermal exposure were not selected, based on the lack of toxicity in the rat dermal exposure study and a dermal absorption study demonstrating low (about 2%) absorption of methoxyfenozide in the 80WP formulation.  An oral study was not selected because the appropriate studies either showed no toxicity at any dose tested, or the parameters affected in oral studies (e.g., hematologic changes) were examined but showed no treatment-related changes in the dermal study.

A.3.5	Inhalation Exposure (Short- and Intermediate-Term)

Study Selected:  Two-week range-finding study for the subchronic dietary study in the dog
MRID No.:  44617722
Executive Summary:  See Appendix A, Guideline [§ 870.3150]
Dose and Endpoint for Risk Assessment: NOAEL = 16.8 mg/kg/day, based on hematological changes seen at LOAEL = 90.8 mg/kg/day.
Comments about Study/Endpoint/Uncertainty Factors:  No short-term or subchronic inhalation toxicity studies were available; an oral study was therefore selected for route-to-route extrapolation.  The dog 2-week dietary range-finding study was selected because it is of an appropriate duration and it identified the most sensitive dose and endpoint for this exposure scenario. Findings included hematological effects (including decreased RBC counts, decreased hemoglobin concentrations, Heinz bodies and changes in RBC morphology, increased reticulocyte counts and methemoglobinemia).  The range-finding study was selected in lieu of the 90-day subchronic dog study because no effects were reported at doses up to about 200 mg/kg/day.  However, in the chronic dog study, mild hematological changes were reported at 14 weeks at the LOAEL of 106 mg/kg/day, with a NOAEL of 9.8 mg/kg/day.  The reason for the early effects is unclear, but it may reflect adaptation of the animals to the test material.  A similar circumstance was observed with the rat two-week and 90-day dietary studies:  thyroid and adrenal effects were observed at lower dose levels in the two-week study (1000 ppm, or estimated 69 mg/kg/day with a NOAEL of 250 ppm or 17 mg/kg/day) whereas the subchronic NOAEL was 1000 ppm with a LOAEL of 5000 ppm or 353 mg/kg/day), based on liver weight increases and hypertrophy.  Decreased body weight was observed in the subchronic mouse dietary study, but no effects were seen in the 18-month carcinogenicity study.

Because only two animals/sex/dose were in each dose group, the NOAEL and LOAEL for this risk assessment were selected from the highest NOAEL and lowest LOAEL from individual animals' average daily compound intake.  The selected dose and endpoint are considered to be conservative endpoints that provide protection from potential hematological effects, which may be transient at the selected study LOAEL, based on the lack of effects in the subchronic dog study.  The study is protective of potential developmental effects, because no developmental or offspring toxicity was observed in any of the available developmental and reproductive toxicity studies.  Although a repeated-dose inhalation toxicity study is not available, the oral study is considered adequately protective, based on the conservative endpoint selected, low vapor pressure of methoxyfenozide, low application rate for current use patterns, and low acute inhalation toxicity; a 10X UFDB is therefore not required.  A combined UF of 100x was utilized (10X each to account for inter- and intra-species variability).
A.4	Executive Summaries

A.4.1	Subchronic Toxicity

	870.3100	90-Day Oral Toxicity - Rat

In a subchronic oral toxicity study (MRID No. 44617722), methoxyfenozide technical (99.2% purity, Lot No. WS-10395, TD No. 92-014) was administered by dietary admix to Charles River Crl:CD BR rats (10/sex/group) at doses of 0, 50, 250, 1000, 5000 or 20,000 (limit dose) ppm (equivalent to average daily intakes of 0, 3.4, 17.0, 69.3, 353.4 or 1368.8 mg/kg/day in males and  0,3.7, 19.1, 72.4, 379.3 and 1,531.2 mg/kg/day in females) for 13 weeks. The following parameters were examined: mortality, clinical signs, body weights, food consumption, ophthalmology, hematology, clinical chemistry, urinalysis, organ weights, macroscopic pathology and microscopic pathology.

The following effects were observed: a statistically significant reduction in red blood cells and hemoglobin in 20,000 ppm females (7-8% less than controls) and slight or moderate periportal hepatocellular hypertrophy in all 5000 and 20,000 ppm males and females compared with none observed in controls or lower dose rats. There were statistically significant increases in relative-to-body weight liver weights in 5000 and 20,000 ppm males as well as in 20,000 ppm females (11-16% above controls). There were increases in absolute liver weights in both sexes at 5000 and 20,000 ppm when compared to controls (+7 to 13% in males and +9 to 10% in females), however these increases were not statistically significant.

[It is noted that in the 2-week range-finding study, which tested at 0, 50, 250, 1000, 5000 and 20,000 ppm, some effects were observed which were not observed in the 13-week study, and these findings were seen at a lower dose than the LOAEL for the subchronic study.  At 1000 ppm, follicular cell thyroid follicular cell hypertrophy/hyperplasia in 3/5 males and 2/5 females, and minimal hypertrophy of the adrenal gland zona fasciculata in 1/5 female (all vs. 0/5 controls) were observed; these effects were also seen at higher doses.  At >=5000 ppm, liver absolute and relative weights in males, adrenal absolute and relative weights in females, and hepatocellular hypertrophy in females were also increased.  Necrosis of hepatocytes was observed in males at 20,000 ppm.]

The LOAEL (subchronic study only) is 5000 ppm (353.4/379.3 mg/kg/day, males/females), based on effects on the liver (increased absolute and relative weights, and periportal hepatocellular hypertrophy in both sexes).  The NOAEL is 1000 ppm (69.3/72.4 mg/kg/day in males/females).

This study is classified Acceptable/guideline and satisfies the data requirement for OPPTS §870.3100 for a three-month oral toxicity study in rats.

	870.3100	90-Day Oral Toxicity - Mouse

In a. subchronic toxicity study (MRID No. 44617723), methoxyfenozide technical (99.2% purity, Lot No. WS-10395, TD No. 92-014) was administered by dietary admix to Charles River Crl:CD-1 (ICR) BR VAF/+ mice (10/sex/group) at doses of 0, 70, 700, 2500 or 7000 ppm (equivalent to average daily intakes of 0, 11.9, 112.5, 428.2 or 1149.3 mg/kg/day in males and 0, 17.4, 165.1, 589.4 and 1742.1 mg/kg/day in females) for 13 weeks. The following parameters were examined: mortality, clinical signs, body weights, feed consumption, hematology, clinical chemistry, organ weights, macroscopic pathology and microscopic pathology.

There were no clinical signs and all mice survived until scheduled sacrifice. Body weight gains in the 7,000 ppm group were less than respective controls for males (18%) and females (15%) for the 13-week period. Food consumption did not appear to be altered. There were no apparent effects on the following parameters: hematology, clinical chemistry, organ weights, macroscopic pathology or microscopic pathology.

The LOAEL is 7000 ppm (1149.3/1742.1 mg/kg/day in males/females; limit dose), based on a decrease in body weight gain in males and females.  The NOAEL is 2500 ppm (428.2/589.4 mg/kg/day in males/females).

This study is classified acceptable/guideline and satisfies the data requirement for a subchronic oral toxicity study in the mouse (OPPTS §870.3100).

	870.3150	90-Day Oral Toxicity - Dog

In a subchronic toxicity study (MRID No.44617724), methoxyfenozide technical (99.8% purity, Lot No. WS-10395, TD No. 92-014) was administered by dietary admix to Hazleton Research Products beagle dogs (4/sex/group) at doses of 0, 15, 50, 500 or 5000 ppm (equivalent to average daily intakes of 0, 0.6, 2.0, 21.4 or 197.5 mg/kg/day in males and 0, 0.6, 1.9, 20.4 or 208.8 mg/kg/day in females) for 13 weeks. The 15 ppm group was then dosed for an additional 2 weeks at 15 ppm, followed by an increase in dose to 15,000 ppm for another 6 weeks. The doses in mg/kg/day for the additional 6 weeks were 422.0 mg/kg/day for males and 460.4 mg/kg/day for females. No control animals were kept beyond the original 13 weeks for comparison with these higher dose levels.  The following parameters were examined:  mortality, clinical signs, ophthalmology, body weights, feed consumption, hematology, clinical chemistry, urinalysis, organ weights, macroscopic pathology and microscopic pathology.

There was the suggestion (no statistical significance) that 5000 ppm caused a decrease in body weight gain in both sexes over the 13-week period (males: controls = 3.7 kg, 5000 ppm 3.3 kg; females: controls = 3.0 kg, 5000 ppm = 2.4 kg).  However, these differences were not considered sufficient to establish an adverse effect.  All dogs treated with 15,000 ppm for the 6 additional weeks gained weight. However, there was no additional control group with which to compare the results.  No other parameters were affected by test article administration.

[Results of a two week range-finding study were also provided in this report, which dosed 2 dogs/sex/group at 0, 300, 3500, 7000, 15,000 or 30,000 ppm (equivalent to individual animal intakes of 0, 11.7-14.7, 141.6-167.6, 264.7-370.4, 571.4-631.7 or 1113.7-1337.0 mg/kg/day for males and 0, 13.3-16.8, 90.8-184.8, 285.9-336.8, 582.3-630.9 or 1092.6-1169.1 mg/kg/day for females).  Although there were no clear-cut definitive effects on any hematology parameters in the 13-week study, in the 2-week range-finding study, there were decreases for all animals of both sexes in RBC count (13-20%), hemoglobin (9-18%) and hematocrit (8-16%) for all animals of both sexes at >=3500 ppm after two weeks when compared with the pre-dose values.  Methemoglobinemia and abnormal RBC morphology (Heinz bodies, Howell-Jolly bodies, polychromasia) were reported as well.  Increased spleen weights were also observed at >=3500 ppm.  Bilirubinemia was observed at >=7000 ppm in males.  No effects were identified in the range-finding study at 300 ppm.

The NOAEL (subchronic study only) is 5000 ppm (197.5/208.8 mg/kg/day, males/females; HDT).  A LOAEL was not determined (>5000 ppm).

This study is classified acceptable/guideline and satisfies the data requirement for a three-month toxicity study in dogs (OPPTS §870.3150).  Although a LOAEL was not achieved, toxicity was observed in a two-week range-finding study and an acceptable chronic dog toxicity study is available (MRID 44617728).

	870.3200	28-Day Dermal Toxicity  -  Rat

In a 28-day repeated dose dermal toxicity study (MRID 44617725), groups of 10 male and 10 female Crl:CD(R)BR rats were treated with RH-2485 Technical (98%, Lot No. 1), by dermal application to shaved skin moistened with tap water and held in place by dermal occlusion, at doses of 0, 75, 300, or 1000 mg/kg/day for 6 hours/day, 5 days/week.

No mortality was recorded, and there were no clinical signs indicative of systemic toxicity at any treatment level. No treatment-related dermal irritation was produced. Additionally, there were no treatment-related effects on body weight, food consumption, absolute or relative organ weight, hematology, or clinical chemistry in either sex of rats. No gross or microscopic changes in either sex were found to be caused by the treatments.

The systemic NOAEL is 1000 mg/kg/day (HDT).  The systemic LOAEL was not determined for either male or female rats (>1000 mg/kg/day). The dermal NOAEL was 1000 mg/kg/day.  The dermal LOAEL was not established (>1000 mg/kg/day).

This study is classified as Acceptable/guideline and satisfies the guideline requirement for a 28-day dermal study in rats (OPPTS §870.3200). Although a LOAEL was not established, the highest dose tested (1000 mg/kg) is the limit dose.

	870.3465	90-Day Inhalation  -  Rat

Not required and not submitted

A.4.2	Prenatal Developmental Toxicity

	870.3700a Prenatal Developmental Toxicity Study - Rat

In a developmental toxicity study (MRID No. 44638201), methoxyfenozide technical (99.2% purity) was administered by gavage to Charles River Crl:CD BR VAF/Plus (Sprague-Dawley) rats (25/group) at doses of 0 (0.5% aqueous methylcellulose vehicle), 100, 300 or 1,000 mg/kg/day on gestation days 6 through 15.  The following parameters were examined: maternal (clinical signs, morbidity, mortality, body weights, food consumption, corpora lutea, implantation sites, resorption sites, abdominal/thoracic cavities and the position of live/dead fetuses) and fetuses (weights, external changes, Bouin's soft tissue examination and skeletal changes).

Maternal toxicity:  There were no deaths or clinical signs, nor where there any effects on body weights or food consumption.  No changes were noted in any of the reproductive parameters.  The maternal NOAEL is 1,000 mg/kg/day (HDT, limit dose).  A maternal LOAEL was not determined (>1,000 mg/kg/day).

Developmental toxicity:  Fetal examinations did not reveal any affects on body weight or gross/visceral/skeletal aspects.  The developmental NOAEL is 1,000 mg/kg/day.  A developmental LOAEL was not determined (>1,000 mg/kg/day).

This study is classified Acceptable/guideline and satisfies the guideline criteria for a developmental toxicity study in the rat (OPPTS §870.3700a).

	870.3700b Prenatal Developmental Toxicity Study - Rabbit

In a developmental toxicity study (MRID No. 44617726), methoxyfenozide technical (98.0% purity) was administered by gavage to Hazleton Research Products New Zealand White rabbits (16/group) at doses of 0 (0.5% aqueous methylcellulose vehicle), 100, 300 or 1,000 mg/kg/day on gestation days 7 through 19.  The following parameters were examined: maternal (clinical signs, morbidity, mortality, body weights, food consumption, corpora lutea, implantation sites, resorption sites, abdominal/thoracic cavities and the position of live/dead fetuses) and fetuses (weights, external changes, soft tissue examination, brain, eyes and skeletal changes).

Maternal toxicity:  There were no deaths or clinical signs, nor where there any effects on body weights or food consumption.  No changes were noted in any of the reproductive parameters.  The maternal NOAEL is 1,000 mg/kg/day (HDT, limit dose).  A maternal LOAEL was not determined (>1,000 mg/kg/day).

Developmental toxicity:  Fetal examinations did not reveal any affects on body weight or gross/visceral/skeletal aspects.  The developmental NOAEL is 1,000 mg/kg/day.  A developmental LOAEL was not determined (>1,000 mg/kg/day).

This study is classified Acceptable/guideline and satisfies the guideline criteria for a developmental toxicity study in the rabbit (OPPTS §870.3700b).

A.4.3	Reproductive Toxicity

	870.3800 Reproduction and Fertility Effects - Rat

In a two-generation reproduction study (MRID 44617727), RH-2485 Technical  (98.0% a.i.) was administered to 30 Crl:CD(R)BR rats/sex/dose in the diet at concentrations of 0, 200, 2000, or 20,000 ppm (equivalent to average daily intake for P1 males of 0, 15.4, 153.4, or 1551.9 mg/kg/day, respectively; for P1 females of 0, 17.9, 180.7, or 1820.7 mg/kg/day, respectively; for P2 males of 0, 19.1, 193.1, or 1956.0 mg/kg/day, respectively; and for P2 females of 0, 20.4, 202.7, or 2036.5 mg/kg/day, respectively).  Treatment was continuous throughout the study.  The two parental generations, P1 and P2, produced one litter of pups each (F1 and F2, respectively).  The parental animals received the test diet for 10 weeks before mating and throughout mating, pregnancy, and lactation of their litters.  Pups were selected from the F1 litters to parent the F2 generation.  The P1 generation produced 22 to 27 litters/group consisting of liveborn pups, the P2 generation produced 24 to 28 liveborn litters/group.

Parental toxicity:   In this study, the target organ for the systemic toxicity of RH-2485 Technical to adult rats was the liver.  For the P1 and P2 males and females exposed to 20,000 ppm, the absolute and relative terminal liver weights were significantly increased by 13 to 27% (p<0.05), in comparison to control values.  Microscopic changes in the liver included midzonal to periportal hepatocellular hypertrophy in all of the animals of both generations at 20,000 ppm, and in females, only, at 2000 ppm.   The incidence rates for hepatocellular hypertrophy at 0, 200, 2,000 and 20,000 ppm were as follows: 0/30, 0/30, 0/30, and 30/30 (100%), respectively, for the P1 and P2 males:  0/30, 0/30, 4/30 (13.3%) and 30/30 (100%), respectively, for the P1 females; and 0/30, 0/30, 1/30 (3.3%), and 30/30 (100%), respectively, for the P2 females.

Statistically significant reductions (p<0.05) in body weights and cumulative body weight gains were observed among the high-dose P1 males during the last 12 weeks of the study; however, the reductions were never more than 7% ( p<0.05), in comparison to control values; the overall body weight gain (weeks 0-20) for this group was depressed by 10% (p<0.05).  Body weights, food consumption, and body-weight gains were comparable to, or significantly higher than, control values for the P2 males throughout the study and for the P1 and P2 females during premating, gestation, and lactation.  Therefore, the biological significance of the reduced body weights of the P1 males is questionable.

The following parameters of systemic toxicity were comparable for RH-2485 Technical-treated and control P1 and P2 males and females: mortality, clinical signs, gross pathology, relative and absolute terminal weights of the reproductive organs, and microscopic pathology of the reproductive organs.  The LOAEL for parental toxicity is 20,000 ppm (1551.9 mg/kg/day), based on increased absolute and relative liver weights in males and females and on hepatocellular hypertrophy in males and females.  The NOAEL for parental toxicity is 2000 ppm (153.4 mg/kg/day).

Offspring toxicity:  Treated F1 and F2 litters were comparable to control litters with regard to macroscopic abnormalities, malformations, or variations; number of liveborn pups (total and per litter); number of live pups/litter on days 4, 7, 14, or 21 of lactation; the number of stillborn pups (total and per litter); body weights on days 0, 4, 7, 14, and 21 of lactation; sexual maturity; sex ratios; anogenital distance; and indices of survival.  The NOAEL for offspring toxicity is 20,000 ppm (1551.9 mg/kg/day; HDT).  A LOAEL for offspring toxicity was not established (>20,000 ppm).

Reproductive toxicity:  There were no treatment-related reproductive effects on the P1 and P2 males and females or their F1 and F2 offspring.  The endpoints of reproductive function and performance for P1 and P2 parental generations were comparable for RH-2485 Technical-treated and control animals with regard to the following:  length and periodicity of the estrous cycle; copulatory interval; number of females inseminated and/or pregnant; length of gestation; sperm motility, morphology, and concentration; and indices of mating, fertility, and gestation.  The NOAEL for reproductive toxicity is >20,000 ppm (1551.9 mg/kg/day).  The LOAEL for reproductive toxicity was not identified (>20,000 ppm).

This study is classified Acceptable/guideline and satisfies the guideline criteria for a reproductive toxicity study in the rat (OPPTS §870.3800).
A.4.4	Chronic Toxicity

	870.4100a (870.4300) Chronic Toxicity  -  Rat

See 870.4300, below

	870.4100b Chronic Toxicity - Dog

In a chronic oral toxicity study (MRID 44617728), RH-2486 technical (methoxyfenozide, 98.9% a.i., Lot No. 1, TD94-134) was administered in the diet to 4 beagle dogs/sex/dose at dietary concentrations of 0, 60, 300, 3000 or 30,000 ppm for 52 weeks (equivalent to average daily intakes of 0, 2.2, 9.8, 106.1 or 1152.4 mg/kg/day in males and 0, 2.2, 12.6, 110.6 or 1199.2 mg/kg/day in females).

The most notable compound-related hematologic effects consisted of methemoglobinemia, nucleated red blood cells (RBCs) and mild hemolysis, particularly in females.  At 3000 ppm, mild hematological effects were observed by 14 weeks of treatment.  Methemoglobinemia was observed in males (increased to 157-167% of controls) and females (153-183% of controls) at most or all time points.  In males, platelets were significantly increased (156-163%) at all time points and RBCs were significantly decreased at week 14.  Hct, Hg and RBCs were generally decreased in females throughout the study (13-18%), but only occasionally achieved statistical significance.  No overt clinical signs of treatment-related toxicity were observed, and survival, body weights, body weight gains and food consumption were also unaffected by compound administration.

At 30,000 ppm, hematological effects were more pronounced and increased cellularity of the rib and sternum marrow were observed in 1-2 males and females.  Absolute and relative liver weight were slightly increased (10-24%), but only absolute weight in males was statistically significant (24% above controls).  An increase in pigmented macrophages was observed in the liver and spleen in 1-3 animals in both sexes.  Absolute and relative thyroid weights were increased (144%/163%), but there was no corresponding histopathology.  Bilirubinemia in males was also observed.

The LOAEL is 3000 ppm (106.1/110.6 mg/kg/day in males/females), based on hematological effects including mild anemia and methemoglobinemia.  The NOAEL is 300 ppm (9.8/12.6 mg/kg/day in males/females).

This study is classified Acceptable/guideline and satisfies the guideline criteria for a chronic oral toxicity study in the dog (OPPTS §870.4100b).

A.4.5	Carcinogenicity

	870.4200a Carcinogenicity Study - rat

See 870.4300, below

	870.4200b Carcinogenicity (feeding)  -  Mouse

In a carcinogenicity feeding study (MRID 44617729), RH-2485 (98.0% a.i.; Sample No. 94-134, Lot No. 1) was administered to 60 Crl:CD-1 (ICR) BR (VAF/+) mice/sex/dose in the diet at concentrations of 0, 70, 2800 or 7000 ppm for 18 months (intake for males: 0, 10.0, 405, or 1020 mg/kg/day; for females: 0, 12.8, 529, or 1354 mg/kg/day).

No toxicologically significant differences were found between the treated and control animals of either sex.  Clinical signs, survival, body weight, and food consumption were comparable in treated and control animals.  The lower lymphocyte count and alterations in kidney and testes weights in males were small in magnitude ( 16%, p < 0.05), not dose-related, and/or lacked histopathological correlates.  There were no treatment-related gross or microscopic lesions.

The NOAEL is 7000 ppm (1020/1354 mg/kg/day for males/females)(HDT). A LOAEL was not established in this study (> 7000 ppm).

There was no evidence of carcinogenicity in male or female mice.  The incidence of neoplasms found in numerous organs and tissues was comparable in treated and control groups.  The animals were dosed adequately since their intake exceeded the limit dose of 1000 mg/kg/day.

Discussion of Tumor Data:  There was no evidence of carcinogenicity in this study.

Adequacy of the Dose Levels Tested:  In this study, methoxyfenozide was administered at adequate dose levels for carcinogenicity testing since it was tested at the limit dose of 7000 ppm (1020 mg/kg/day in males and 1354 mg/kg/day in females).

This study is classified Acceptable/guideline and satisfies the guideline requirement for a dietary carcinogenicity study in the mouse (OPPTS §870.4200b)

	870.4300 Chronic toxicity/carcinogenicity (feeding)  -  Rat

In a combined chronic toxicity /carcinogenicity study (MRID 44617731), RH-2485 technical (methoxyfenozide 98% a.i.; Lot Number 1, TD94-134) was administered in the diet to 70 male and 70 female Crl:CD[(R)]BR rats per group at concentrations of 0, 200, 8000, or 20,000 ppm (0, 10.2, 411, or 1045 mg/kg/day for males and 0, 11.9, 491, or 1248 mg/kg/day for females) for up to 99 weeks in males (only 89 weeks in the 20,000-ppm group) and 95 weeks in females except for 10 animals per sex per dose that were sacrificed at 52 weeks for interim evaluation.

Survival was adversely affected in males at the 20,000-ppm dose level.  Survival rates to week 89 in the 0 and 20,000-ppm groups in the main experiment on males were 28/60 (53% dead) and 17/60 (72% dead), respectively, with this difference being significant, p<0.05 as calculated by reviewer.  The only significant (p<0.05) effects on absolute body weight, body-weight gain, and food efficiency were in the 20,000-ppm females.  In approximately the last year of the experi - ment, reductions in absolute body weight were often to a level of slightly less than 90% that of the control.  At the end of the experiment, absolute body weight was reduced 17% in females.  Reductions in body-weight gain were often to a level of about 80% of the control.  Reductions in food efficiency were about 11% and 49% in the first and second years, respectively.

Treatment-related and significant (p<0.05) hematology changes at the two higher doses consisted of small reductions (less than 10% compared to control) in RBC counts, hemoglobin concentrations, and/or hematocrit, and these effects were seen in both sexes.  At the highest dose, there were significant (p<0.05) increases in methemoglobin over the control in both sexes, and there was a significant (p<0.05) increase in platelet counts over control in females.  Clinical chemistry evaluations in both sexes at the two higher doses showed significant (p<0.05) and probably treatment-related increases in serum levels of gamma glutamyl transpeptidase (GGT) and reductions in total bilirubin in the serum.  These two effects on clinical chemistry are of uncertain, and probably unlikely, biological significance.

The liver, kidneys and thyroid were identified as targets for RH-2485 Technical toxicity.  Significant increases (p<0.05) were found in absolute and relative liver weights compared to control in both sexes at the 20,000 ppm dose.  These ranged up to 23% increase in males and 24% increase in females at the terminal sacrifice.  At the 8000 ppm dose in males at 52 weeks, a significant increase (p<0.05) was found in relative liver weight (19%) and a non-significant increase was found in absolute liver weight (21%).  These changes are consistent with the finding of much increased and significant (p<0.01) incidences of periportal hepatocellular hypertrophy in both sexes at both the 8000- and 20,000-ppm doses.  At the terminal sacrifice, the incidences of this lesion in control males and females were 2% and 3%, respectively.   [Here and below in this paragraph, percents refer to all animals in the main study.]  In contrast, in males of the 8000- and 20,000-ppm groups, the incidences were 35% and 53%, respectively.  In females of these same groups at the terminal sacrifice, the incidences were 40% and 70%, respectively.  An increase in the incidence of the more serious manifestations of chronic progressive glomerulonephropathy is thought to have increased the mortality rate of males fed 20,000-ppm of the test substance.  Microscopic analysis demonstrated two treatment-related lesions in the thyroid at the terminal sacrifice: 1) follicular cell hypertrophy in 8000-ppm males (25%, not significant) and 20,000-ppm males (31%, p<0.05) compared with 13% in controls; 2)  altered colloid in 8000 ppm males (22%, not significant) and 20,000 ppm males (24%, not significant) compared with 12% in controls as well as in 20,000-ppm females (38%, p<0.01) compared with 17% in controls.  Increases were found at the terminal sacrifice for absolute and relative weights of adrenal glands compared to controls in 20,000-ppm males (up to 25%, not significant) and in 20,000 ppm females (up to 100%, p<0.05 for relative weight).  Similar increases were found at the terminal sacrifice for absolute and relative weights of adrenal glands compared to controls in 8000-ppm males (up to 55%, not significant) and in 8000 ppm females (up to 31%, not significant).  Numerous other treatment-related microscopic lesions were identified only in 20,000-ppm females (mainly mineralizations of tissues found in from 713% of the animals); these were considered secondary changes attributable to uremia that resulted from the chronic progressive glomerulonephropathy.  No effects attributable to the test material were observed at 200 ppm.  The LOAEL is 8000 ppm (411 mg/kg/day for males and 491 mg/kg/day for females), based on hematological changes (decreased RBC counts, hemoglobin concentrations, and/or hematocrit in males and females), liver toxicity (increased liver weights in males and periportal hepatocellular hypertrophy in males and females), histopathological changes in the thyroid (increased follicular hypertrophy and altered colloid in males) and possible adrenal toxicity (increased adrenal weights in males and females).  The absence of treatment-related effects identifies a NOAEL of 200 ppm (10.2 mg/kg/day for males and 11.9 mg/kg/day for females).

No evidence of carcinogenicity was observed in rats fed RH-2485 Technical at dietary concentrations of 200, 8000, or 20,000 ppm for up to 99 weeks.  Dosing was considered adequate because of the decreases in body weights, body-weight gain, and food efficiency in female rats fed the 20,000-ppm diet and because of the decrease in survival in male rats fed the 20,000-ppm diet.  The highest dose tested for both males and females is also higher than the limit dose of 1000 mg/kg/day.

This study is classified Acceptable/guideline and satisfies the guideline requirement for a dietary carcinogenicity study in the rat (OPPTS §870.4200a)

A.4.6	Mutagenicity

	Gene Mutation
870.5100 Bacterial reverse gene mutation assay (S. typhimurium strains TA 98, TA100, TA1535, TA1537
MRID 44617728
Acceptable/guideline
Dose range
Negative for gene mutation up to insoluble  concentrations (precipitation observed at >=2000 ug/plate) in the presence or absence of S9 metabolic activation
870.5100 Bacterial reverse gene mutation assay (S. typhimurium strains TA 98, TA100, TA1535, TA1537
MRID 44617733
Acceptable/guideline
Dose range 50 to 5000 ug/plate, test material RH-117,236 (metabolite of methoxyfenozide)
Negative for gene mutation up to insoluble concentrations (precipitation observed at 5000 ug/plate) in the presence or absence of S9 metabolic activation.
870.5300 Mammalian in vitro cell forward gene mutation assay (CHO cells)
MRID 44617734
Acceptable/guideline
Dose range 0.1 to 1250 ug/mL.
Negative for gene mutation up to insoluble concentrations (precipitation observed at >=100 ug/mL) in the presence or absence of S9 metabolic activation.

	Cytogenetics
870.5375, Mammalian in vitro chromosomal aberration assay (CHO cells)
MRID 44617735
Acceptable/guideline
Dose range 0.21 to 1250 ug/mL.
Negative for increased frequency of chromosomal aberration, up to concentrations (>=50 ug/mL) at which the mitotic indices were decreased, in the presence or absence of S9 metabolic activation.

	Other Genotoxicity
870.5395, Mouse micronucleus assay
MRID 44617801
Acceptable/guideline
Dose range 500 to 5000 mg/kg (single IP dose).
Negative for increased frequency of micronucleus formation in CD-1 mice at 24 or 48 hrs postdosing up to the limit dose for this assay.

A.4.7	Neurotoxicity

	870.6100 Delayed Neurotoxicity Study - Hen

Not required and not submitted

	870.6200 Acute Neurotoxicity Screening Battery

In an acute oral neurotoxicity study (MRID 44617802), groups of 10 Crl:CD(R)BR  rats/sex/group were administered single gavage doses of RH-2485 technical (Toxicology Department Sample Number 94-134; Lot No. 1; 98 % active ingredient) at 0 (control), 500, 1000, or 2000 mg a.i./kg. The active ingredient was suspended in 0.5% aqueous methylcellulose and administered at a constant volume of 20 ml/kg. Functional observational battery (FOB) and motor activity (MA) testing were performed prior to administration and within 3 hours (time of peak effect) of dosing (day 0), and on days 7 and 14 post-dose.  Body weights were recorded pre-test, weekly during the study period and on FOB assessment days. Clinical signs were recorded daily. At necropsy all rats were perfused in situ and given a limited gross necropsy; six rats/sex/dose (high-dose and control) were further processed for neuropathological evaluation at study termination.

All animals survived to scheduled termination.  Daily cage-side observations revealed no overt signs of treatment-related effects in males or females at any exposure concentration.  No treatment-related effects on body weight were observed during the study.

There were no observable signs of a neurotoxic effect even at the highest concentration in females.  FOB assessment on Day 0 (3 hours after dosing) revealed a decrease in hindlimb grip strength (% below controls) for males in the 2000 mg/kg group. MA assessment remained comparable to controls throughout the study for males and females in all exposure groups.

No neuropathological endpoints were observed during the histological examinations of the peripheral or central nervous systems of these animals at any exposure concentration.

Based on the absence of any substance-related effects on body weight or body weight gain and any clinical signs of toxicity, the NOAEL for systemic toxicity is a concentration of 2000 mg/kg for males and females. The NOAEL for neurotoxic effects is 2000 mg/kg for females. Based on a decrease in hindlimb grip strength on day 0 in the 2000 mg/kg male group, the NOAEL for males is 1000 mg/kg and the LOAEL for males is 2000 mg/kg. No LOAEL was established for systemic effects in males or females or for neurotoxic effects in females.

This study is classified as Acceptable/guideline and satisfies the guideline requirement for an acute oral neurotoxicity screening study in the rat (OPPTS §870.6200a).

	870.6200 Subchronic Neurotoxicity Screening Battery

In a subchronic oral neurotoxicity study (MRID 44617803), groups of Crl:CD(R)BR rats (10 rats/sex/group) were administered concentrations of 0, 200, 2000 or 20,000 ppm of RH-2485 technical (Toxicology Department Sample Number 94-0134; Lot No. 1; 98 % active ingredient) in the diet for 3 months. These doses resulted in average daily intake values of 0, 13, 130, and 1318 mg/kg/day for males and 0, 16, 159, and 1577 mg/kg/day in females for 0, 200, 2000, and 20,000 ppm, respectively. Functional observational battery (FOB) and motor activity (MA) testing were performed prior to administration and in the 4[th], 8[th], and 13[th] week of the administration period.  Body weights were recorded pre-test, weekly during the study period and on FOB assessment days. Food consumption was determined weekly for each animal. All rats surviving to necropsy were perfused in situ and given a limited gross necropsy. Six/rats/sex/dose (high-dose and control) were further processed for neuropathological evaluation at study termination.

One male in the 20,000 ppm group was found dead during week 5 of the study; this death was attributed to a urethral obstruction and was not considered to be treatment-related. All animals in all other exposure groups survived to scheduled termination.

Daily cage-side observations and weekly physical examinations revealed no overt signs of treatment-related effects in males or females at any exposure concentration. No treatment-related effects on body weight, body weight gain, or food consumption were observed during the study.

There were no observable signs of a neurotoxic effect even at the highest concentration in males or females.  FOB and MA remained comparable to controls throughout the study and no neuropathological endpoints were observed during the histological examinations of these animals at any exposure concentration.

Based on the absence of any substance-related effects on body weight or body weight gain and any clinical signs of toxicity, the NOAEL for systemic toxicity is 20,000 ppm for males (1318 mg/kg/day) and females (1577 mg/kg/day). The NOAEL for neurotoxic effects is 20,000 ppm (1318/1577 mg/kg/day in males/females).  A LOAEL was not established for either systemic or neurotoxic effects (>20,000 ppm).

This study is classified as Acceptable/guideline and satisfies the guideline requirement for a subchronic oral neurobehavioral screening study in the rat (§870.6200b).

	870.6300 Developmental Neurotoxicity Study

Not required and not submitted

A.4.8	Metabolism

	870.7485	Metabolism  -  Rat

In an oral metabolism study (MRID 44617804), groups of five Crl:CD(R)BR rats/sex/dose group received methoxyfenozide (technical grade, several lots labeled at different positions with radiochemical purity ranging from 96.4 to 99.0%) according to the following schedules:  a single low dose (10 mg/kg labeled with [14] C at the t-butyl, A-ring or B-ring); high dose (1000 mg/kg labeled at the t-butyl or A-ring); or diets containing 10 mg/kg unlabeled test material for two weeks, followed by a single 10 mg/kg gavage dose of test material labeled on the A-ring.  Other groups of 3-6 male and 3-6 female rats received five daily doses of 10 mg/kg test material labeled on the A-ring or a single low- or high-dose of test material labeled at the t-butyl or A-ring to determine pharmacokinetics and tissue distribution. One additional group of 4 male and 4 female cannulated rats received a single low-dose of test material labeled on the A-ring to determine biliary excretion. In a preliminary study, expired air was collected from male and female rats that received 1000 mg/kg test material labeled at the t-butyl, A-ring, or B-ring positions. It was found that < 0.1% of the administered dose was removed in this manner and no further expired air studies were done.

No test material-related deaths occurred and mass balance, ranging from 93-104%, was acceptable. The total plasma elimination rate for male and female rats was longer for high dose relative to low dose animals; suggestive of metabolic pathway saturation. This particular effect was more prominent with female rats, regardless of label position. Following absorption, the test
material was rapidly metabolized and excreted. The highest radiolabel tissue concentrations at Cmax (0.25 hours post-treatment) were found in the intestinal tract, stomach, and liver, respectively, although at Cmax the liver contained <9% of the administered dose. By 1/2 Cmax, (1-2 hours post-treatment), radiolabel concentrations in the stomach and liver had decreased to <3% of the dose but remained relatively constant in the intestinal tract. Male and female cannulated rats excreted 62-70% of the administered dose into the bile and urine, indicating that absorption would at least be equivalent. By five days after treatment, the highest concentrations of radioactivity were found in the liver (<0.2% of dose) and carcass (<0.1% of dose) with <0.01% of the dose in other tissues and organs. No apparent effects attributable to label position or sex were noted.

The test material was excreted primarily into the feces with approximately 86-97% of a 10 mg/kg or 1000 mg/kg dose eliminated by this route. Urinary excretion was relatively minor and accounted for 5-13% of the administered dose. No substantial quantitative differences in the urine and fecal excretion profiles for the different radiolabel positions were observed.

Elimination of the radiolabel by all treatment groups and both sexes was essentially complete within 48 hours of treatment.

Before excretion, the test material was metabolized principally by O-demethylation and oxidative hydroxylation on the A-ring phenyl and/or B-ring methyl groups followed by glucuronic acid or sulfate conjugation. Cleavage of the amide linkage from either the A-ring or B-ring side and conjugation with glycine to form the corresponding substituted hippuric acid metabolite was a minor route. No significant sex-related differences in the metabolic disposition of the test material were noted, although there were some minor sex-related differences. No significant dose-dependent differences in metabolic disposition were found.

This metabolism study in the rat is classified as Acceptable/guideline and satisfies the guideline requirement for a general metabolism study (OPPTS §870.7485) in the rat.

	870.7600	Dermal Absorption - Rat

In an in vivo dermal penetration study (MRID 44638202), four male rats per experimental group were dosed by dermal application to shaved skin of methoxyfenozide as either the a-ring labeled [14]C-RH-1 12,485 80WP (80% a.i.) or the 2F formulation (2% a.i.) at 0.25, 0.025 or 0.0025 mg/cm[2] a.i. for 1, 10 or 24 hours.

Percent absorption of the 80WP formulation at 24 hours was 0.64, 1.02 and 1.83 for the respective high to low doses. After washing, 8.90, 9.53 and 7.35 percent of the dose remained in the washed skin.  Percent absorption of the 2F formulation at 24 hours was 0.44, 0.83 and 3.20 for the respective high to low doses.  After washing, 6.40, 8.85 and 10.64 percent of the dose remained in the washed skin.  Because of the combination effects of the low doses used and the low rates of absorption, the sample assay values tended to be scattered. The absorption patterns of the two formulations overlapped with no apparent differences. Because of the absorption pattern, the quantity remaining in the skin is not expected to add significantly to the total absorbed and should not be used for risk assessment.

This study is classified as Acceptable/guideline and satisfies the guideline requirement for a dermal absorption study in the rat (OPPTS §870.7600).

A.4.9	Immunotoxicity

	870.7800	Immunotoxicity

In an immunotoxicity study (MRID 48592601), Methoxyfenozide (98.0% a.i., Lot #6329B01) was administered to female Crl:CD(SD) rats (10/dose) in the diet targeted to deliver nominal doses of 0, 75, 300, or 1000 mg/kg bw/day (actual doses of 0, 76.9, 324, or 1076 mg/kg bw/day, respectively) for 28 days. On Day 25, animals in all groups were immunized with a suspension of sheep red blood cells (SRBC) by intravenous injection (2x10[8] SRBC/animal, 0.5 mL/animal dose volume). Animals in the positive control group received an intraperitoneal injection of cyclophosphamide at a dose of 20 mg/kg bw (1 mL/kg bw dose volume) on Days 24-28. All animals were evaluated for mortality, clinical signs, body weight changes, and gross pathology. The vehicle control and test substance treatment groups also were evaluated for food consumption and hematologic parameters. Immunotoxicity was assessed for all animals by an Enzyme-linked Immunosorbent Assay (ELISA). Spleen and thymus weights were measured at necropsy (Day 29) for all animals; liver weights were measured for the vehicle control and test substance treatment groups.

There were no test substance treatment-related effects on mortality, clinical signs, body weight changes, food consumption, or hematologic parameters. A statistically significant increase in relative but not absolute liver weight was found in the 300 and 1000 mg/kg bw/day groups; one animal in the 1000 mg/kg bw/day group also had a grossly observable enlarged liver. These increases in liver weights were treatment-related and are consistent with previously reported results.

The systemic toxicity LOAEL for Methoxyfenozide in female rats is 300 mg/kg bw/day (actual dose of 324 mg/kg bw/day), based on increased relative liver weight which was consistent with previously reported results. The NOAEL for systemic toxicity is 75 mg/kg bw/day (actual dose of 76.9 mg/kg bw/day).

For immunotoxicity, there were no test substance treatment-related effects on thymus and spleen weights or serum anti-SRBC IgM antibody levels as measured by an ELISA. A high inter-individual variability of anti-SRBC antibody level was noted in all the treatment groups as well as in the control group. Evaluation of individual animal data of this study did not show any trend or distribution that would demonstrate significant suppression of anti-SRBC antibody response. Animals in the positive control group showed marked decreases of anti-SRBC abtibody response. The positive control group confirmed the ability of the test system to detect immuno-suppressive effects and confirmed the validity of the study design.

The Natural Killer (NK) cells activity was not evaluated in this study. The toxicology database for Methoxyfenozide does not reveal any evidence of treatment-related effects on the immune system. The only potential evidence of immunotoxicity in the submitted studies was anemia and other related blood effects observed in rats and dogs; however, additional parameters indicated these effects were compensatory response to the anemia, which was observed primarily after chronic dosing. The overall weight of evidence suggests that this chemical does not directly target the immune system. Under HED guidance, a NK cells activity assay is not required at this time.

Under conditions of this study, the immunotoxicity NOAEL is 1000 mg/kg/day (actual dose of 1076 mg/kg/day); the LOAEL was not established.

This immunotoxicity study is classified acceptable/guideline and satisfies the guideline requirement for an immunotoxicity study (OPPTS 870.7800) in rats.

Appendix B.	Physical/Chemical Properties.

TABLE 2	 Physicochemical Properties of Methoxyfenozide.
                                   Parameter
                                     Value
                                   Reference
Molecular Weight
368.47
D231303; H. Podall; 19 May 1997
Melting point/range (ºC)
206.1-208

pH
7.0

Density (g/cm[3])
0.740 +- 0.0081

Water solubility (mg/L at 20ºC)
3.3

Solvent solubility (g/L at 20ºC)
N-heptane	1.87
Xylene	3.38
1,2-dichloroethane	36.72
Methanol	192.92
2-Propanol	50.22

Vapor pressure (25ºC)
1.33 x 10[-5] Pa (1 x 10[-7] mm Hg)

Dissociation constant, pKa
None

Octanol/water partition coefficient (Log [KOW])
3.72 +- 0.04

UV/visible absorption (max)
ε 55313 at 203 nm
European Commission; SANCO/10384/202  -  rev. 4; 7 October 2004

Appendix C.  Review of Human Research

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 data, which include studies from the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler Exposure Task Force (AHETF) database; and the Outdoor Residential Exposure Task Force (ORETF) database; are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements.  For certain studies that review may have included review by the Human Studies Review Board.  Descriptions of data sources as well as guidance on their use can be found at http://www.epa.gov/pesticides/science/handler-exposure-data.html and http://www.epa.gov/pesticides/science/post-app-exposure-data.html.


[Federal Register Volume 82, Number 225 (Friday, November 24, 2017)]
[Notices]
[Page 55847]
[FR Doc No: 2017-25418]

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DEPARTMENT OF HOMELAND SECURITY

Coast Guard

[Docket No. USCG-2017-1023]

Certificate of Alternative Compliance for the TUG BERT REINAUER

AGENCY: Coast Guard, DHS.

ACTION: Notice.

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SUMMARY: The Coast Guard has issued a Certificate of Alternative
Compliance (COAC) to the TUG BERT REINAUER because it is a vessel of
special construction or purpose, that, with respect to the position of
its navigation and towing lights, is not able to fully comply with the
provisions of the International Regulations for Preventing Collisions
at Sea, 1972, without interfering with the normal operation of the
vessel. Our publication of this notice fulfills a statutory requirement
and promotes maritime security.

DATES: The Certificate of Alternative Compliance was issued on November
16, 2017.

FOR FURTHER INFORMATION CONTACT: For information or questions about
this notice call or email Mr. Kevin Miller, First District Towing
Vessel/Barge Safety Specialist, U.S. Coast Guard; telephone (617) 223-
8272, email [email protected].

SUPPLEMENTARY INFORMATION: The United States is signatory to the
International Maritime Organization's International Regulations for
Preventing Collisions at Sea, 1972 (72 COLREGS), as amended. The
special construction or purpose of some vessels makes them unable to
comply with the light, shape, and sound signal provisions of the 72
COLREGS. Under statutory law \1\ and Coast Guard regulation,\2\ a
vessel may instead meet alternative requirements and the vessel's
owner, builder, operator, or agent may apply for a Certificate of
Alternate Compliance (COAC).
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    \1\ 33 U.S.C. 1605(c).
    \2\ 33 CFR 81.3.
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    For vessels of special construction, the cognizant Coast Guard
District Office determines whether the vessel for which the COAC is
sought complies as closely as possible with the 72 COLREGS, and decides
whether to issue the COAC. The Coast Guard issued a COAC to the TUG
BERT REINAUER on November 16, 2017. That COAC will remain valid until
information supplied in the COAC application or the COAC terms become
inapplicable to the vessel.
    Under the governing statute \3\ and regulation,\4\ the Coast Guard
must publish notice of having issued this COAC. This notice promotes
maritime safety by informing vessels that may encounter the TUG BERT
REINAUER to expect alternative positioning of its navigation and towing
lights.
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    \3\ 33 U.S.C. 1605(c).
    \4\ 33 CFR 81.18.
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    The Commandant, U.S. Coast Guard, certifies that the TUG BERT
REINAUER is a vessel of special construction or purpose, and that, with
respect to the position of the navigation and towing lights, it is not
possible to comply fully with the requirements of the provisions
enumerated in the 72 COLREGS, without interfering with the normal
operation of the vessel. The Commandant further finds and certifies
that the sidelights (9' 7'' from the vessel's side mounted on the pilot
house) are in the closet possible compliance with the applicable
provisions of the 72 COLREGS and that full compliance with the 72
COLREGS would not significantly enhance the safety of the vessel's
operation.
    This notice is issued under authority of 33 U.S.C. 1605(c) and 33
CFR 81.18.

    Dated: November 20, 2017.
Byron L. Black,
Prevention Chief, First Coast Guard District.
[FR Doc. 2017-25418 Filed 11-22-17; 8:45 am]
 BILLING CODE 9110-04-P


[Federal Register: December 19, 2008 (Volume 73, Number 245)]
[Notices]
[Page 77869]
[DOCID:fr19de08-194]

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DEPARTMENT OF TRANSPORTATION

Federal Railroad Administration

Petition for Waiver of Compliance

    In accordance with Part 211 of Title 49 Code of Federal Regulations
(CFR), notice is hereby given that the Federal Railroad Administration
(FRA) received a request for a waiver of compliance with certain
requirements of its safety standards. The individual petition is
described below, including the party seeking relief, the regulatory
provisions involved, the nature of the relief being requested, and the
petitioner's arguments in favour of relief.

Port Authority Trans-Hudson Corporation

[Docket Number FRA-2008-0135]

    The Port Authority Trans-Hudson Corporation (PATH) seek a permanent
waiver of compliance with the Locomotive Safety Standards, 49 CFR
229.123, which requires that each lead locomotive be equipped with an
end plate that extends across both rails, a pilot or a snowplow. The
petition is being made for PATH's new fleet of passenger MU locomotives
designated as PA-5 cars. Prior to receiving this new fleet of cars,
PATH had been granted a waiver, Docket Number LI-81-9, from the pilot
end plate requirement. PATH operated under this waiver over the past 26
years. PATH operates a closed system with no public highway-rail
crossings over 13.8 miles between New York, and New Jersey. PATH states
that the addition of a pilot would interfere with space allocated for
Communication Based Train Control Equipment to be mounted under the
cars.
    Interested parties are invited to participate in these proceedings
by submitting written views, data, or comments. FRA does not anticipate
scheduling a public hearing in connection with these proceedings since
the facts do not appear to warrant a hearing. If any interested party
desires an opportunity for oral comment, they should notify FRA, in
writing, before the end of the comment period and specify the basis for
their request.
    All communications concerning these proceedings should identify the
appropriate docket number (e.g., Waiver Petition Docket Number FRA-
2008-0135) and may be submitted by any of the following methods:
     Web site: http://www.regulations.gov. Follow the online
instructions for submitting comments.
     Fax:<PHONE_NUMBER>.
     Mail: Docket Operations Facility, U.S. Department of
Transportation, 1200 New Jersey Avenue, SE., W12-140, Washington, DC
20590.
     Hand Delivery: 1200 New Jersey Avenue, SE., Room W12-140,
Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday,
except Federal holidays.
    Communications received within 45 days of the date of this notice
will be considered by FRA before final action is taken. Comments
received after that date will be considered as far as practicable. All
written communications concerning these proceedings are available for
examination during regular business hours (9 a.m.-5 p.m.) at the above
facility. All documents in the public docket are also available for
inspection and copying on the Internet at the docket facility's Web
site at http://www.regulations.gov.
    Anyone is able to search the electronic form of any written
communications and comments received into any of our dockets by the
name of the individual submitting the comment (or signing the comment,
if submitted on behalf of an association, business, labor union, etc.).
You may review DOT's complete Privacy Act Statement in the Federal
Register published on April 11, 2000 (Volume 65, Number 70; Pages
19477-78).

    Issued in Washington, DC on December 15, 2008.
Grady C. Cothen, Jr.,
Deputy Associate Administrator for Safety Standards and Program
Development.
 [FR Doc. E8-30157 Filed 12-18-08; 8:45 am]

BILLING CODE 4910-06-P


[Federal Register Volume 77, Number 220 (Wednesday, November 14, 2012)]
[Notices]
[Pages 67820-67823]
[FR Doc No: 2012-27580]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-N-0911]

Privacy Act of 1974; Report of a New System of Records; Food and
Drug Administration User Fee System

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of a new system of records.

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SUMMARY: In accordance with the requirements of the Privacy Act of 1974
and the Food and Drug Administration's (FDA) regulations for the
protection of privacy, FDA is publishing notice of a Privacy Act system
of records entitled, ``FDA User Fee System, HHS/FDA,'' System Number
09-10-0021. FDA utilizes the User Fee System (UFS) to collect fees
pursuant to Federal law and FDA's implementing regulations. The records
kept in this system relate to fees assessed under the Freedom of
Information Act (FOIA), the Prescription Drug User Fee Act, the Medical
Device User Fee and Modernization Act, the Animal Drug User Fee Act,
the Animal Generic Drug User Fee Act, the Mammography Quality Standards
Act, the Family Smoking Prevention and Tobacco Control Act, the Food
Safety Modernization Act, the Biosimilar User Fee Act, the Generic Drug
User Fee Act, and other fees assessed by FDA under its Federal Food,
Drug and Cosmetic Act authority such as color additive certification
fees and export certificate fees. For purposes of this notice, these
fees are collectively referred to as user fees.

DATES: Effective Date: The new system of records will be effective on
November 14, 2012, with the exception of the routine uses. The routine
uses will become effective on December 31, 2012. Submit either
electronic or written comments by December 31, 2012.

ADDRESSES: You may submit comments, identified by Docket No. FDA-2012-
N-0911, by any of the following methods:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.

Written Submissions

    Submit written submissions in the following ways:
     Fax:<PHONE_NUMBER>.
     Mail/Hand delivery/Courier (for paper or CD-ROM
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Agency name
and Docket No. FDA-2012-N-0911 for this notice. All comments received
may be posted without change to http://www.regulations.gov, including
any personal information provided. For additional information on
submitting comments, see the ``Comments'' heading of the SUPPLEMENTARY
INFORMATION section of this document.
    Docket: For access to the docket to read background documents or
comments received, go to http://www.regulations.gov and insert the
docket number, found in brackets in the heading of this document, into
the ``Search'' box and follow the prompts and/or go to the Division of
Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Lisa Berry, Office of Financial
Management,

Food and Drug Administration, 1350 Piccard Dr., suite 200A, Rockville,
MD 20850,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Description of the System of Records

    The UFS is a billing and collections system that maintains
information about the individuals, organizations, and companies
required to pay user fees. Information maintained in the UFS includes:
     Contact person's name, phone number, fax number, and email
address;
     Federal Employer Identification Number (FEIN) for entity
remitters;
     Taxpayer Identification Number (TIN) for individual
remitters, which is encrypted with only the last four characters
visible (in some circumstances individual remitters may use a Social
Security Number as the TIN);
     Company name or the Organization name; and
     Data Universal Numbering System (DUNS) number and business
address.
    The UFS also stores application details as the fee remitter
(submitter) creates coversheets to pay user fees. These details
include, but are not limited to, the type of application, waiver and
exemption status, and Small Business Decision (SBD) Number. When a
submitter generates a coversheet the UFS will only print the last four
characters of the FEIN/TIN along with the organization name and
address.
    Additionally, the UFS stores billing details, adjustments to
invoices, and payment receipt information including date, mode, and
amount of payment.

II. Routine Use Disclosures of Information in the System

    The Privacy Act allows FDA to disclose information without an
individual's consent if the information is to be used for a purpose
that is compatible with the purpose(s) for which the information was
collected. Any such compatible use of data is known as a ``routine
use.'' The routine uses in this system meet the compatibility
requirement of the Privacy Act.
    A number of the routine uses listed in the System of Records Notice
below are common to systems across the government. These include
routine uses allowing disclosure to Federal Agencies as necessary in
order to respond to a confirmed or suspected breach of system security
or confidentiality (routine use number 1); to the Department of Justice
(DOJ) to obtain DOJ advice on producing user fee records in response to
a FOIA request (routine use 2); to DOJ when DOJ represents the Agency
in litigation (routine use 7); in response to a subpoena issued by a
duly empowered Federal Agency (routine use 3); to a court or tribunal
when the records are relevant and necessary to a proceeding involving
the Agency or an employee (routine use 8); to contractors and others
who perform services for the Agency related to the UFS (routine use 9);
to the National Archives and Records Administration (NARA) and General
Services Administration as needed in the course of records management
inspections (routine use 10); and to the Department of Homeland
Security (DHS) in circumstances where system records are captured in an
intrusion detection program and made accessible to DHS (routine use
11).
    Additional routine uses specific to the UFS allow disclosure to
entities as permitted under the Debt Collection Improvement Act
(routine use 4); to banks in order to process payment made by credit
card (routine use 5); and to Dun and Bradstreet to validate submitter
contact information (routine use 6).

SYSTEM NUMBER:
    09-10-0021.

SYSTEM NAME:
    FDA User Fee System, HHS/FDA.

SECURITY CLASSIFICATION:
    Unclassified.

SYSTEM LOCATION:
    This system is located at FDA's Data Center in Ashburn, VA.

CATEGORIES OF INDIVIDUALS COVERED BY THE SYSTEM:
    This system contains records about individuals and companies that
are required to submit user fee payments to the FDA. This includes
organizations registered in the UFS, those billed through the system,
as well as those submitting applications for review or otherwise
assessed fees under the User Fee Program.
    Privacy Act notification, access, and amendment rights relative to
the UFS are available only to individuals who are the subject of
records in this system. User fee record subjects are individuals
required to pay a user fee, including individual FOIA requestors and
individuals who are sole proprietors of an entity required to pay a
user fee. Although records in the system may contain personally
identifiable information (PII) related to other individuals, only the
specified fee submitters are considered subjects of records in this
system.

CATEGORIES OF RECORDS IN THE SYSTEM:
    1. The UFS maintains information about individuals, companies and
organizations that pay user fees. This includes: (a) For an entity
remitter, a FEIN, and for an individual remitter, a TIN; (b) company or
organization name and address; (c) DUNS number; and (d) contact
person's name, phone number, Fax number, and email address.
    2. The UFS also stores application information collected when the
fee remitter (submitter) creates coversheets in order to pay user fees.
This information includes the type of application, waiver and exemption
status, and SBD number.
    3. The UFS stores fee processing information including: Billing
details; adjustments to invoices including credit and debit memos; and
receipt information including date, mode, and amount of payment.

AUTHORITY FOR MAINTENANCE OF THE SYSTEM:
    21 U.S.C. 371, 379, 379e, 379h, 379h-1, 379j, 379j-12, 379j-21,
379j-31, 387s, and 393(d)(2); 42 U.S.C. 263b(r)(1); 5 U.S.C. 301, 552;
and 44 U.S.C. 3101.

PURPOSE(S):
    FDA personnel and any contractors assisting them will use
information in the system, on a need-to-know basis, for the following
purposes:
    1. To assess and collect user fees.
    2. To provide an electronic payment and receipt mechanism that is
integrated with the U.S. Department of Treasury's http://www.Pay.gov
Web site and the various FDA Centers.
    3. To provide Web-based capabilities including transactional
inquiries and information on payment status.
    4. To facilitate debt collection activities in accordance with the
Debt Collection Improvement Act of 1996 and the HHS regulations for
claims collections (45 CFR Part 30).

ROUTINE USES OF RECORDS MAINTAINED IN THE SYSTEM INCLUDING THE PURPOSES
OF SUCH USES AND CATEGORIES OF USERS:
    Permitted disclosures include those made in accordance with routine
uses that are listed in the notice of the system of records. 5 U.S.C.
552a(b)(3). The Privacy Act defines ``routine use'' as ``with respect
to the disclosure of a record, the use of such record for a purpose
which is compatible with the purpose for which it was collected.'' See
also FDA's Privacy Act regulations, defining ``routine use'' as ``use
outside the Department of Health and Human Services that is compatible
with the purpose for which the records were collected and described in
the [System of Records] notice * * *'' 21 CFR 21.20(b)(5).

    Records in this system that contain information about record
subjects and nonsubjects (such as FDA employees who operate the system)
may be disclosed to recipients outside HHS in accordance with the
following routine uses:
    1. Records may be disclosed to appropriate Federal Agencies and
Department contractors that have a need to know the information for the
purpose of assisting the Department's efforts to respond to a suspected
or confirmed breach of the security or confidentiality of information
maintained in this system of records.
    2. In the event HHS deems it desirable or necessary, in determining
whether particular records are required to be disclosed under the FOIA,
disclosure may be made to the DOJ for the purpose of obtaining its
advice.
    3. Where Federal Agencies having the power to subpoena other
Federal Agencies' records, such as the Internal Revenue Service, issue
a subpoena to HHS for records in this system of records, HHS will make
such records available, provided however, that in each case, HHS
determines that such disclosure is compatible with the purpose for
which the records were collected.
    4. A record from this system may be disclosed to entities as
provided for in the Debt Collection Improvement Act of 1996 (Pub. L.
104-134).
    5. A record may be disclosed to banks enrolled in the Treasury
Credit Card Network to collect a payment or debt when the person has
given his/her credit card number for this purpose.
    6. UFS submitter data (name, address, DUNS number) may be provided
to Dun and Bradstreet for validation for the purpose of maintaining
database integrity.
    7. Disclosure may be made to the Department of Justice (DOJ) when:
(a) The Agency or any component thereof; (b) any employee of the Agency
in his or her official capacity; (c) any employee of the Agency in his
or her individual capacity where the DOJ has agreed to represent the
employee; or (d) the U.S. Government is a party to litigation or has an
interest in such litigation, and by careful review, the Agency
determines that the records are both relevant and necessary to the
litigation and the use of such records by the DOJ is therefore deemed
by the Agency to be for a purpose that is compatible with the purpose
for which the Agency collected the records.
    8. Disclosure may be made to a court or other tribunal, when: (a)
The Agency or any component thereof; (b) any employee of the Agency in
his or her official capacity; (c) any employee of the Agency in his or
her individual capacity where the DOJ has agreed to represent the
employee; or (d) the U.S. Government is a party to the proceeding or
has an interest in such proceeding, and by careful review, the Agency
determines that the records are both relevant and necessary to the
proceeding and the use of such records is therefore deemed by the
Agency to be for a purpose that is compatible with the purpose for
which the Agency collected the records.
    9. Disclosure may be made to contractors and other individuals who
perform services for the Agency related to this system of records, and
who need access to the records in order to perform such services.
Recipients shall be required to comply with the requirements of the
Privacy Act of 1974, as amended, 5 U.S.C. 552a.
    10. Disclosure may be made to NARA and/or the General Services
Administration for the purpose of records management inspections
conducted under authority of 44 U.S.C. 2904 and 2906.
    11. Records may become accessible to U.S. Department of Homeland
Security (DHS) cyber security personnel, if captured in an intrusion
detection system used by HHS/FDA and DHS pursuant to the DHS Einstein 2
program. Under Einstein 2, DHS uses intrusion detection systems to
monitor Internet traffic to and from Federal computer networks to
prevent malicious computer code from reaching the networks. According
to DHS' Privacy Impact Assessment for Einstein 2 (available on the DHS
Cybersecurity privacy Web site, http://www.dhs.gov), only PII that is
directly related to a malicious code security incident is captured by
and accessible to DHS, and DHS does not access PII unless the PII is
part of the malicious code.

POLICIES AND PRACTICES FOR STORING, RETRIEVING, ACCESSING, RETAINING,
AND DISPOSING OF RECORDS IN THE SYSTEM:
STORAGE:
    Records may be maintained in hard copy files and on computer disks,
hard drives, file servers, and other types of data storage devices.

RETRIEVABILITY:
    Records may be retrieved by computer search using name, address,
contact information, system identifiable numbers (party/organization,
submitter numbers), DUNS Number, and payment information (for refunds).

SAFEGUARDS:
    1. Authorized users: Access is restricted to FDA employees and
contractors with a Level 5 or higher clearance who have a need for the
records in the performance of their duties.
    2. Procedural and technical safeguards: Technical controls include
identification and authentication, access control, audit and
accountability, system and communication protection, timely account
disablement/deletion, configuration management, maintenance, system and
information integrity, media protection, and incident response. These
controls extend to remote users as well. Additionally, when a remitter
(submitter) generates a coversheet the UFS will only print the last
four characters of the FEIN/TIN along with the Organization name and
address.
    3. Physical safeguards: Physical security safeguards include
controlled-access buildings where all records (CDs, computer listings,
and paper documents) are maintained in secured areas, locked buildings,
locked rooms, and locked cabinets.

RETENTION AND DISPOSAL:
    UFS records are maintained in accordance with FDA's Records Control
Schedule, and with the applicable General Records Schedule (GRS) and
disposition schedule approved by NARA. UFS records fall under GRS 20,
Items 2a(4) (hard copy input records), 12 and 16 (Output records and
reports), and NARA approved citation N1-088-09-11, Items 1.1 (files
maintained in the Office of Financial Management), 1.2 (data maintained
by FDA Centers), and 1.3.2 (database records).

SYSTEM MANAGER AND ADDRESS:
    George Brindza, Division of Systems, FDA Office of Information
Management (OIM), 2094 Gaither Rd., rm. 131, Rockville, MD 20850; 301-
796-7845.

NOTIFICATION PROCEDURES:
    In accordance with 21 CFR part 21, subpart D, an individual may
submit a request to the FDA Privacy Act Coordinator, with a notarized
signature, to confirm whether records exist about him or her. Requests
should be directed to the FDA Privacy Act Coordinator, Division of
Freedom of Information, 12420 Parklawn Dr., ELEM-1036, Rockville, MD
20857. An individual requesting notification via mail should certify in
his or her request that he or she is the individual who he or she
claims to be and that he or she understands that the knowing and
willful request for or acquisition of a

record pertaining to an individual under false pretenses is a criminal
offense under the Act subject to a $5,000 fine, and indicate on the
envelope and in a prominent manner in the request letter that he or she
is making a ``Privacy Act Request.'' Additional details regarding
notification request procedures appear in 21 CFR part 21, subpart D.

RECORD ACCESS PROCEDURES:
    Procedures are the same as above, in Notification Procedures.
Requesters should also reasonably specify the record contents being
sought. Some records may be exempt from access under 5 U.S.C.
552a(d)(5), if they are ``compiled in reasonable anticipation of a
civil action or proceeding.'' If access to requested records is denied,
the requester may appeal the denial to the FDA Commissioner. Additional
details regarding record access procedures and identity verification
requirements appear in 21 CFR part 21, subpart D.

CONTESTING RECORD PROCEDURES:
    In addition to the procedures described above, requesters should
reasonably identify the record, specify the information they are
contesting, state the corrective action sought and the reasons for the
correction, and provide justifying information showing why the record
is not accurate, complete, timely, or relevant. Rules and procedures
regarding amendment of Privacy Act records appear in 21 CFR part 21,
subpart E.

RECORD SOURCE CATEGORIES:
    Information in this system is obtained from many sources,
including: (1) Directly from the individual, company or organization
that is required to submit user fees to FDA; (2) from materials
supplied by the submitter or individual acting on his/her behalf; (3)
from FDA Centers such as the Center for Drug Evaluation and Research,
Center for Devices and Radiological Health, Center for Biologics
Evaluation and Research, Center for Veterinary Medicine, Center for
Tobacco Products, Center for Food Safety and Applied Nutrition, and the
Office of Financial Management; and (4) from any other relevant source.

RECORDS EXEMPTED FROM CERTAIN PROVISIONS OF THE PRIVACY ACT:
    None.

    Dated: November 7, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-27580 Filed 11-13-12; 8:45 am]
BILLING CODE 4160-01-P


[Federal Register: September 29, 2010 (Volume 75, Number 188)]
[Notices]
[Page 60114-60116]
[DOCID:fr29se10-64]

-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OPP-2010-0248; FRL-8845-9]

Notice of Receipt of Requests for Amendments to Delete Uses in
Certain Pesticide Registrations

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: In accordance with section 6(f)(1) of the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA), as amended, EPA is issuing a
notice of receipt of request for amendments by registrants to delete
uses in certain pesticide registrations. Section 6(f)(1) of FIFRA
provides that a registrant of a pesticide product may at any time
request that any of its pesticide registrations be amended to delete
one or more uses. FIFRA further provides that, before acting on the
request, EPA must publish a notice of receipt of any request in the
Federal Register.

DATES: The deletions are effective March 28, 2011, unless the Agency
receives a written withdrawal request on or before March 28, 2011. The
Agency will consider a withdrawal request postmarked no later than Mach
28, 2011.
    Users of these products who desire continued use on crops or sites
being deleted should contact the applicable registrant on or before
March 28, 2011.

ADDRESSES: Submit your withdrawal request, identified by docket
identification (ID) number EPA-HQ-OPP-2010-0248, by one of the
following methods:
     Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
     Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket Facility's normal hours of operation (8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays).
Special arrangements should be made for deliveries of boxed
information. The Docket Facility telephone number is<PHONE_NUMBER>.

FOR FURTHER INFORMATION CONTACT: Christopher Green, Information
Technology and Resources Management Division, Office of Pesticide
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001; telephone number:<PHONE_NUMBER>; e-mail
address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    This action is directed to the public in general. Although this
action may be of particular interest to persons who produce or use
pesticides, the Agency has not attempted to describe all the specific
entities that may be affected by this action. If you have any questions
regarding the information in this notice, consult the person listed
under FOR FURTHER INFORMATION CONTACT.

B. How Can I Get Copies of this Document and Other Related Information?

    EPA has established a docket for this action under docket ID number
EPA-HQ-OPP-2010-0248. Publicly available docket materials are available
either in the electronic docket at http://www.regulations.gov, or, if
only available in hard copy, at the Office of Pesticide Programs (OPP)
Regulatory Public Docket in Rm. S-4400, One Potomac Yard (South Bldg.),
2777 S. Crystal Dr., Arlington, VA. The hours of operation of this
Docket Facility are from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
305-5805.

II. What Action is the Agency Taking?

    This notice announces receipt by the Agency of applications from
registrants to delete uses in certain pesticide registrations. These
registrations are listed in Table 1 of this unit by registration
number, product name, active ingredient, and specific uses deleted:

               Table 1.--Requests for Amendments to Delete Uses in Certain Pesticide Registrations
----------------------------------------------------------------------------------------------------------------
         EPA Registration No.                Product Name          Active Ingredient        Delete from Label
----------------------------------------------------------------------------------------------------------------
228-675                                Nufarm Diquat SPC 2 L    Diquat dibromide         Soybeans and Sorghum
                                        Herbicide
----------------------------------------------------------------------------------------------------------------
1381-190                               Sterling Herbicide       Benzoic acid             Cotton and Rest Areas
----------------------------------------------------------------------------------------------------------------
10163-196                              Prefar 4E                Bensulide                Residential Uses
----------------------------------------------------------------------------------------------------------------
10163-198                              Prefar 4E                Bensulide                Residential Uses
----------------------------------------------------------------------------------------------------------------
10163-199                              Prefar 4E                Bensulide                Residential Uses
----------------------------------------------------------------------------------------------------------------
10163-200                              Prefar 4E                Bensulide                Field Grown Flowers,
                                                                                Bulbs, Ornamentals and
                                                                                Tank Mix
                                                                                Recommendation with
                                                                                Alanap
----------------------------------------------------------------------------------------------------------------
10163-204                              Prefar 4E                Bensulide                Residential Uses
----------------------------------------------------------------------------------------------------------------
34688-76                               Aquatreat DNM-30         Nabam and Sodium         Fuel Oils, Lubricating
                                                                 dimethyldithiocarbamat   Oils and Hydraulic
                                                                 e                        Fluids in Marine
                                                                                Environments
----------------------------------------------------------------------------------------------------------------
67064-2                                Admiral Liquid           Acid Blue 9              Fish Farms and Fish
                                                                                Hatcheries
----------------------------------------------------------------------------------------------------------------
82633-2                                Sharda Diquat            Diquat dibromide         Sorghum (seed crop
                                        Concentrate                                       only) and Soybean
                                                                                (seed crop only)
----------------------------------------------------------------------------------------------------------------
83529-13                               Diquash Ag               Diquat dibromide         Sorghum (seed crop
                                                                                only) and Soybean
                                                                                (seed crop only)
----------------------------------------------------------------------------------------------------------------

    Users of these products who desire continued use on crops or sites
being deleted should contact the applicable registrant before March 28,
2011 to discuss withdrawal of the application for amendment. This 180-
day period

will also permit interested members of the public to intercede with
registrants prior to the Agency's approval of the deletion.
    Table 2 of this unit includes the names and addresses of record for
all registrants of the products listed in Table 1 of this unit, in
sequence by EPA company number.

  Table 2.--Registrants Requesting Amendments to Delete Uses in Certain
                         Pesticide Registrations
------------------------------------------------------------------------
            EPA Company Number                Company Name and Address
------------------------------------------------------------------------
228                                         Nufarm Americas, Inc.
                                            150 Harvester Drive
                                            Suite 200
                                            Burr Ridge, IL 60527
------------------------------------------------------------------------
1381                                        Winfield Solutions, LLC.
                                            P.O. Box 64589
                                            MS 5705
                                            St. Paul, MN 55164-0589
------------------------------------------------------------------------
10163                                       Gowan, Co.
                                            P.O. Box 5569
                                            Yuma, AZ 85366-5569
------------------------------------------------------------------------
34688                                       Akzo Nobel Surface
                                             Chemistry, LLC.
                                            7140 Heritage Village Plaza
                                            Gainesville, VA 20156
------------------------------------------------------------------------
67064                                       Becker Underwood, Inc.
                                            801 Dayton Avenue
                                            Ames, IA 50010
------------------------------------------------------------------------
82633                                       Sharda Worldwide Exports Pvt
                                             Ltd.
                                            7460 Lancaster Pike
                                            Suite 9
                                            Hockessin, DE 19707
------------------------------------------------------------------------
83529                                       Sharda USA, LLC.
                                            7460 Lancaster Pike
                                            Suite 9
                                            Hockessin, DE 19707
------------------------------------------------------------------------

III. What is the Agency's Authority for Taking this Action?

    Section 6(f)(1) of FIFRA provides that a registrant of a pesticide
product may at any time request that any of its pesticide registrations
be amended to delete one or more uses. The FIFRA further provides that,
before acting on the request, EPA must publish a notice of receipt of
any such request in the Federal Register. Thereafter, the Administrator
may approve such a request.

IV. Procedures for Withdrawal of Request

    Registrants who choose to withdraw a request for use deletion must
submit the withdrawal in writing to Christopher Green using the methods
in ADDRESSES. The Agency will consider written withdrawal requests
postmarked no later than March 28, 2011.

V. Provisions for Disposition of Existing Stocks

    The Agency has authorized the registrants to sell or distribute
product under the previously approved labeling for a period of 18
months after approval of the revision, unless other restrictions have
been imposed, as in special review actions.

List of Subjects

    Environmental protection, Pesticides and pests.

    Dated: September 21, 2010.
 Oscar Morales,
Director, Information Technology and Resouurces Management Division,
Office of Pesticide Programs.

[FR Doc. 2010-24314 Filed 9-28-10; 8:45 am]
BILLING CODE 6560-50-S