LOAEL = 143 mg/kg/day based on decreased body weights in females, increased serum total bilirubin in both sexes, increased incidences of eosinophilic foci in livers in males, centrilobular hypertrophy in both sexes, centrilobular fatty infiltration in males, interstitial fibrosis in the lungs in females, and heart failure cells in lungs in both sexes
No evidence of carcinogenicity
870.4300b

Combined Chronic/ Carcinogenicity (mouse)
00100527 (1981)
Acceptable, guideline
♂♀: 0, 40, 120, 360, or 1080 ppm
♂: 0, 5, 14, 41, 134 mg/kg/day
♀: 0, 5, 15, 44, 143 mg/kg/day
NOAEL = 14 mg/kg/day
LOAEL = 41 mg/kg/day based on hepatocellular hypertrophy and liver fatty degeneration in males
At 134/143 mg/kg/day (♂/♀): in males - ↓BW, ↑ liver weight, ↑ALT, ↑AST, hepatocellular hypertrophy, focal granulomatous inflammation, fatty degeneration in liver; in females - ↑ liver weight, fatty degeneration in liver
No evidence of carcinogenicity
870.5100

Genotoxicity
Bacterial gene mutation assay
00153604
Acceptable, guideline

Negative
870.5100

Genotoxicity
Bacterial gene mutation assay
41885904
Acceptable, guideline
Concentrations of 313-5000 ug/mL
Negative
870.5100

Genotoxicity
Bacterial gene mutation assay
41915901
Acceptable, guideline
Concentrations of 312-5000 ug/mL
Negative
870.5300

Genotoxicity
In vitro mammalian cell gene mutation
00155130
Unacceptable, guideline
Highest dose tested: 5000 ug/mL
Negative
This report was lacking a description of the procedures actually used in performing this study.
870.5300

Genotoxicity
In vitro mammalian cell gene mutation
41421301
Acceptable, guideline
Concentrations of 500-5000 ug/mL
Negative
870.5300

Genotoxicity
In vitro mammalian cell gene mutation
00130710
Acceptable, guideline
Highest dose tested: 10,000 mg/kg
Negative
870.5300

Genotoxicity
In vitro mammalian cell gene mutation
00138950
Acceptable, guideline

Negative
870.5550

Genotoxicity
Unscheduled DNA synthesis (rat hepatocyte cells)
41885905
Acceptable, guideline
Concentrations of 10-507 ug/mL
Negative
870.5915

Genotoxicity
In vivo sister chromatid exchange (Chinese hamster bone marrow)
41475206
Acceptable, guideline
0, 0.5, 1.67, 5 g/kg
Negative
870.6200a

Acute neurotoxicity screening battery
Not submitted and not required.
-
870.6200b

Subchronic neurotoxicity screening battery
46845301 (2006)
Acceptable, non-guideline
♂♀: 0, 300, 980, 3200 ppm
♂: 0, 18.4, 59.3, 206.9 mg/kg/day
♀: 0, 22.2, 72.0, 234.3 mg/kg/day
NOAEL = 206.9 mg/kg/day
LOAEL was not determined
870.6300

Developmental neurotoxicity
Not submitted and not required
-
870.7485

Metabolism and pharmacokinetics (rat)
00045868 (1980)
00153605 (1985)
Acceptable, guideline

Excretion is extremely rapid and tissue accumulation is negligible, assuming DMSO vehicle does not affect excretion or storage of sethoxydim, 78% excreted into urine and 20% in feces. Administration of radioactively labeled sethoxydim yielded 0.8% radioactivity in urine identified as three hydroxymetabolites.
870.7600
Dermal penetration (species)
Not submitted and not required.
-
870.7800
Immunotoxicity
Not submitted and not required.
-

A.3	Hazard Identification and Endpoint Selection

A.3.1	Acute Reference Dose (aRfD)  -  All Populations

Study selected: Prenatal developmental study in rats
MRID No.:  43092902
Executive Summary:  See Appendix A.4, Guideline OPPTS 870.3700a
Dose and Endpoint for Risk Assessment:  Maternal NOAEL = 180 mg/kg/day; LOAEL = 650 mg/kg/day based on irregular gait that was observed in 12/34 dams on the first day of dosing
Developmental NOAEL = 180 mg/kg/day; LOAEL = 650 mg/kg/day based on decreased fetal body weight, tail abnormalities, and delayed ossification
Comments about Study/Endpoint/Uncertainty Factors:  The selected endpoints are the lowest values for this exposure scenario and are the most protective.  The fetal anomalies are presumed to occur following a single dose in utero and, thus, this endpoint would be applicable to females 13-50 years of age.  A 100-fold uncertainty factor (10X interspecies and 10X intraspecies) was applied.  Thus, an aRfD of 1.8 mg/kg/day was calculated for all populations.  The FQPA SF is 1X; therefore, the aPAD is also 1.8 mg/kg/day.

A.3.2	Chronic Reference Dose (cRfD)

Study selected: Carcinogenicity study in mice
MRID No.:  00100527
Executive Summary:  See Appendix A.4, Guideline OPPTS 870.4200b
Dose and Endpoint for Risk Assessment:  NOAEL = 14 mg/kg/day; LOAEL = 41 mg/kg/day based on liver hypertrophy and fatty degeneration
Comments about Study/Endpoint/Uncertainty Factors:  The selected endpoints are the lowest values for this exposure scenario and are the most protective.  A 100-fold uncertainty factor (10X interspecies and 10X intraspecies) was applied.  Thus, a cRfD of 0.14 mg/kg/day was calculated.  The FQPA SF is 1X; therefore, the cPAD is also 0.14 mg/kg/day.

A.3.3	Incidental Oral Exposure (Short-Term)

Short-Term (1-30 days)

Study selected: Prenatal developmental study in rats
MRID No.:  43092902
Executive Summary:  See Appendix A.4, Guideline OPPTS 870.3700a
Dose and Endpoint for Risk Assessment:  Maternal LOAEL = 650 mg/kg/day based on irregular gait that was observed in 12/34 dams on the first day of dosing
Developmental LOAEL = 650 mg/kg/day based on decreased fetal body weight, tail abnormalities, and delayed ossification
Comments about Study/Endpoint/Uncertainty Factors:  The selected endpoints are the lowest values for this exposure scenario and are the most protective.  The fetal anomalies are presumed to occur following a single dose in utero and, thus, this endpoint would be applicable to females 13-50 years of age.  A 100-fold uncertainty factor (10X interspecies and 10X intraspecies) was applied.  The FQPA SF is 1X.  The residential level of concern for MOE = 100; an occupational LOC is not appropriate for this exposure scenario.

Intermediate-Term (1-6 Months)

Study Selected: No study was selected, because intermediate-term exposure is not anticipated.

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

The HIARC concluded that for all durations of dermal exposure, quantification of non-cancer risk is not required.  No dermal or systemic toxicity was seen following repeated dermal applications at the limit dose (1000 mg/kg/day) in rabbits.  Developmental toxicity occurred at the same dose as maternal toxicity in the rat.  Incomplete ossification of the 6[th] sternebrae was noted in rabbit fetuses at 400 mg/kg/day (the highest dose tested), while no adverse effect was noted in the dams at that dose level.

Dermal Absorption Factor:  A dermal absorption factor was not determined, because a dermal assessment is not required for sethoxydim, and there is no evidence of carcinogenicity or genotoxicity.

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

Study selected: 28-Day inhalation study in rats
MRID No.:  44021202
Executive Summary:  See Appendix A.4, Guideline OPPTS 870.3465
Dose and Endpoint for Risk Assessment:  NOAEL = 0.3 mg/L; LOAEL = 2.4 mg/L based on increased liver weight, increased total serum bilirubin, and increased incidence of slight centrilobular hepatocyte swelling
Comments about Study/Endpoint/Uncertainty Factors:  The dose/endpoint is derived from a study conducted via the appropriate route of concern.  This study was the only inhalation study available, and the HED gives a more protective value than the oral studies.

A.4	Executive Summaries

Executive Summaries are provided below for the studies used in the sethoxydim risk assessment, as well as some other sethoxydim toxicity studies.  Executive Summaries may be available for some of the other guidelines, but not reported here.  However, many of the studies are old and in some cases the Executive Summaries could not be located and in other cases existed in a very truncated form (Tox One-Liners) or in an atypical format.

A.4.1	Subchronic Toxicity

	870.3100	90-Day Oral Toxicity - Rat

MRID 00045859: Protocol: Six groups of six week old Wistar-SLC rats, each group consisting of 20 males and 20 females were fed a diet containing technical NP-55 dissolved in acetone to make the following doses administered for 14 weeks: 2700 ppm, 900 ppm, 300 ppm, 100 ppm, 33 ppm and 0 ppm. Mean NP-55 intakes over the study period in mg/kg/day were as follows for males and females respectively: 196.34 and 200.45 (2700 ppm group), 60.43 and 66.8 (900 ppm group), 20.12 and 21.43 (300 ppm group), 6.75 and 7.08 (100 ppm group), 2.25 and 2.42 (33 ppm group). The 0 ppm group was the vehicle control group (acetone added to diet), Animals were observed daily for mortalities, pharmacotoxic symptoms, physiological changes and central nervous system effects. Body weights were measured weekly. Food consumption was estimated weekly for 4 weeks and biweekly thereafter. Water consumption estimates, urinalysis, hematology tests were done at 4 and 14 weeks. For urinalysis, 10 males and 10 females from each group were tested. For hematology 8 males and 8 females from each group were tested. Blood chemistry, gross necropsies, organ weights and histopathologies were performed on all surviving animals at 14 weeks.

Resu1ts: No mortalities occurred in any groups and no pharmacotoxic signs were observed over the 14 week test period. Total weight gains for the 2700 ppm group were significantly retarded (p < 0.001} but other dosage groups were similar to controls. Food consumption in the 2700 ppm group was depressed but of other groups was similar to controls. Control and experimental groups water consumption were similar. On hematological examination, mean corpuscular hemoglobin decreased for 100 ppm males and increased for females of 100 ppm and 2700 ppm groups. Platelet increases occurred for 100 ppm females, 900 ppm ma1es and females, and 2700 ppm males. Total leucocytes increased in 2700 ppm males and females. Urinalysis showed no significant differences between controls and experimentals. The following differences in blood chemistries between experimentals and controls were noted: protein increased in 33 ppm females, 300 ppm males and females and 2700 ppm males. Albumin increased in 33 ppm and 300 ppm males, but decreased in 300 ppm, 900 ppm and 2700 ppm females. Glutamic pyruvic transaminase decreased in the 2700 ppm group. Alkaline phosphatase decreased in 900 ppm and 2700 ppm females. Glucose decreased in 2700 ppm females. Bilirubin increased in 900 and 2700 ppm groups. Total cholesterol increased in 100 ppm females, 900 ppm males and all of 2700 ppm group. Total calcium increased in 33 ppm males and decreased in 300, 900, and 2700 ppm females.

At gross necropsy, random changes seen in organs of experimentals and controls included thymus petichia, lung, stomach, small intestine and testes changes. Organ weights of liver were increased at high doses, but to a significant level in 900 ppm males and 2700 ppm females. In
2700 ppm males, heart, lung, spleen, kidney and adrenals were significantly decreased in weight. In 2700 ppm females, lung, spleen and adrenals were significantly decreased in weights. Organ/body weight ratios differed from controls as follows: livers of 900 ppm groups and
2700 ppm groups were larger. Brain was larger in the 2700 ppm group, but spleen was smaller. Thymus of females in the 2700 ppm group was smaller. On histopathological examinations, pathological changes were observed in heart, lungs, kidneys, testes and thymus, but were not NP-55 related. However, swollen liver cells at incidences of 100% and 25% in 2700 ppm males and females respectively and at 60% incidence in 900 ppm males were attributable to NP-55 treatment. Such hepatic abnormalities were considered responsible for growth retardation, decreased food efficiency and increased serum cholesterol and bilirubin. The target organ of NP-55 is considered the liver with a no effect leve1 of NP-55 at 300 ppm.

Adverse Effects: The liver at greater than 300 ppm is the target organ for NP-55 in the rat. Associated effects are increases 1n cholesterol and bilirubin and increase in size and organ/body weight ratio of the liver, with swollen cells as histopathological findings.

NOEL = 300 ppm
Core Study - Guidelines.

	870.3100	90-Day Oral Toxicity - Mouse

MRID 00045858: In a 14-week (98-day) oral toxicity study (MRID 00045858) NP-55 (95.9%
a.i., lot #PN-1-1) was administered to 20 ICR mice/sex/dose in the diet at levels of 0, 100, 300,
900, or 2700 ppm (equivalent to 0, 15.4, 45.6, 137.1, or 373.6 mg/kg bw/day for males and 0,
17.2, 52.7, 164.4, or 486.3 mg/kg bw/day for females).

There were no compound-related effects on mortality, clinical signs, body weight, food consumption, hematology, clinical chemistry, or gross pathology. Absolute liver weights of males in the 900 and 2700 ppm groups and of females in the 2700 ppm group were increased by 13 and 33% (both, p<0.01l) and 32% (non-significant), respectively. Hepatocellular hypertrophy was observed microscopically in the livers of these dose groups. Liver weights relative to body weights were also significantly increased in both males and females in the 900 and 2700 ppm dietary groups. The increased liver weights accompanied by histopathological evidence hepatocellular changes are considered treatment-related effects.

The NOAEL for NP-55 in mice is 300 ppm in the diet (males, 45.6 mg/kg/day; females, 52.7 mg/kg/day). The LOAEL is 900 ppm (males, 137.1 mg/kg/day; females, 164.4 mg/kg/day) based on increase liver weight and histopathological evidence of hepatocellular hypertrophy.

This 98-day oral toxicity study in the mouse is Acceptable/Guideline and satisfies the guideline requirement for a 90-day oral toxicity study (OPPTS 870.3100; OECD 408) in the rodent. Although many guideline requirements/recommendations were not fulfilled, these were generally minor deviations that did not impact the results of the study.

	870.3150	90-Day Oral Toxicity - Dog

MRID 00045860: Protocol: Four groups of male beagle dogs (Hazelton Research Animals Inc., Cumberland, Va.) aged 30-34 weeks, weighing between 6.7-13.7 kg, each group consisting of 6 animals, were fed Wayne(R) dog meal containing the following amounts of technical NP-55 for a period of 26 weeks: 0 ppm (control): 120 ppm (3.0 mg/kg/day); 600 ppm (15.0 mg/kg/day) and 3000 ppm (75.0 mg/kg/day). Four similar groups of female dogs weighing between 5.4-11.6 kg were similarly fed for 26 weeks. Appropriate diet was fed once weekly for the first six weeks and twice weekly thereafter, and was available ad libitum. All dogs were observed daily for mortality and signs of pharmacotoxic effects for the first 2 weeks and weekly thereafter. If clinical signs were seen, observations were made daily thereafter. Body weights and food consumption were recorded weekly to week 6 and twice weekly thereafter. Clinical chemistry, hematology and urinalysis were performed on all dogs prior to treatment and at weeks 4. 8, 13 and 26. Blood was collected by jugular puncture. Urine was collected from cage floor runoff except for phenolsulphonthalene determination for which urine was collected by catheterization. Hematology studies included hematocrit, hemoglobin, erythrocyte and platelet counts, total and differential leucocyte counts, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. Clinical chemistry tests included total protein, albumin, alkaline phosphatase, total and direct bilirubin, blood urea nitrogen, calcium, lactic acid dehydrogenase, bromosulphalen dye retention. phenolsulfonphthalen dye excretion, fasting glucose, serum glutamic pyruvic transaminase, serum glutamate- oxaloacetic transaminase, total globulin, albumin/globulin ratio, potassium and total cholesterol. Urinalysis included appearance, pH, specific gravity, glucose, ketones, total protein, bilirubin, urobilinogen, reducing substances and microscopic examination of sediment. Opthalmoscopic examinations were performed initially and terminally on all dogs with an indirect opthalmoscope and a hand held slit limp, using a mydriatic. Surviving dogs were sacrificed after 26 weeks by exsanguination while under the effect of Surital(R) anesthesia. Complete necropsies were done on all dogs and included total body weight measurement and organ/body weight ratio of brain, pituitary, thyroid, heart, liver, lung, kidney, adrenal, testes with epididymis (males) and ovaries (females). Preserved tissues from all dogs which died or were sacrificed were sectioned, stained with hematoxylin and eosin and examined microscopically. These included brain, pituitary, thoracic and lumbar spinal cord, eyes, salivary glands, thyroid with parathyroid, thymus, trachea, esophagus, lungs with bronchi, heart, aorta, liver, gallbladder, spleen, intestine (duodenum, jejunum and ileum), large intestine, mesenteric lymph node, urinary bladder, prostate (males), testes with epididymis (males), ovaries and uterus {females), mammary skin, costachondral junction, bone marrow (femur) and sciatic nerve with adjacent muscle. Statistical comparisons were made on the following: body weight changes (weeks 0-4, 0-8, 0-13, 0-26); food consumption (weeks 4, 8, 13, 26); hematology and clinical chemistry and absolute and relative organ weight data. Data of control groups were compared to treated groups of the same sex by Bartlett's test first and the 1-way classification of variance (ANOVA). If Bartlett's and
ANOVA yielded significant results, a multiple pairwise comparison procedure (Games and Howell) was used to compare group mean values. If only ANOVA gave significant results, Scheffe's multiple pairwise comparison procedure was used to compare group mean values. All analyses were evaluated at the 5% probability level.

Results: Non-treatment related effects included non-specific dermatitis, injected scleras, lacrimation, soft stools or diarrhea, and sores on body. One high-dose male (75 mg/kg/day) was sacrificed moribund as a result of complications due to urinary calculi-obstructed urethra. No other mortalities occurred. No treatment-related behavioral symptoms were noted. The most significant treatment related clinical symptoms included cystitis and/or urinary calculi among low, mid and high dose males observed during catheterization and in the high dose moribund male. One low dose, 2 mid dose and 2 high dose males had such symptoms. Occasional instances of bloody urine were found among low, mid and high dose males. No significant changes in body weights attributable to NP-55 were observed over the 26 week test period. Treatment related changes were found in clinical chemistry, hematology, urinalysis, gross necropsy and histopathology; however, as these results were suspect due to the study design, only a summary of the adverse effects followed by a commentary on the study deficiencies are detailed below.

Adverse Effects:  Random effects on RBC, MCH, SGOT, BIT, and lung weight were seen in 120 ppm (7.5 mg/kg/day) animals. Effects of NP-55 showing a dose-response relationship were seen in 600 ppm and 3000 ppm animals in LDH, A/G, PSP excretion, urinary calculi present, liver and thyroid weight, and pathology in renal pelvis and urinary bladder. A/G ratio of 120 ppm animals showed a dose-response relationship, but this observation was not considered significant. Cystitis was observed in 2/6 males and 3/6 females at the lowest dose, l/6 males and 2/6 females at the mid dose and 2/6 males and 3/6 females at the highest dose. The above effects were not observed in control animals.

NOEL = 120 ppm

Core Study - Minimum data.

Commentary:

   1. NP-55 is reported as slightly unstable at room temperature, but stable at -22°C (Report Cl-C13). In the present study, NP-55 was stored at room temperature from November 30, 1978 to January 4, 1979; then refrigerated from January 4 to March 6, 1979 (study week 6) and frozen from March 6 to termination of the experiment. (In reports C1-Cl3, it was noted that careful procedures were used (i.e. freezing to prevent NP-55 treatment materials from deterioration.)
   2. Dosage of NP-55 were prepared according to the 96.1% purity stated by the sponsor, but no testing was done to confirm purity or to determine if deterioration had occurred during storage.
   3. No report has been received to date concerning homogeneity or accuracy of NP-55 feeding mixture (although sponsor, as per telephone conversation of November, 1980, said this information would be sent).
   4. At the start of the feeding experiment, NP-55 food mixture was offered once weekly for 6 weeks to the young dogs and was available ad libitum, suggesting the possibility that non-uniformity of dosage could easily occur.
   5. The results of this study are at variance with those obtained and reported by Nisso Institute (Reports C12 and Cl3). This is discussed in the accompanying commentary (Report Cl4 Comment):

            Statement for Toxicological Study No. 001. Reason to Make Additional Test of Six Month Dog Feeding Study of NP-55. Nisso Institute for life Science Tab. Report C14 Comment. December 27, 1979; Scientific Comment on Six Month Dog Feeding Study of NP -55.

            This commentary deals with the findings reported by Hazelton Laboratories America Inc., in their six month feeding study, employing a diet of 120 ppm; 600 ppm and 3000 ppm in beagle dogs. In all treated animals a significant decrease in PSP excretion was noted and acute cystitis of urinary bladder and pyelitis of the renal pelvis were observed microscopically. Because Nisso Institute had previously performed two subacute toxicity studies (rat and mouse, see reports Cl2 and C13), Nisso Soda Co. and found the target organ for compound UP-55 was the liver, another subchronic dog feeding study of NP-55 was begun in order to confirm the differences in target between dogs and rodents. The second report is in progress and the final report is expected in January 1981.

Addendum to Twenty-Six Week Toxicity Study in Dogs of NP-55. Report Cl4 Hazelton Laboratories America, Inc. Tab. C14, pp. 1-147. Accession No. 099536. Analysis of Diet, Accession No. 099802, December 8, 1980, pp. 1-3 and Tables 1-5.

Protocol: Two-gram samples of dietary feed in duplicate, were analyzed to determine the concentration of NP-55 in canine food for Project No. 886-103. Three-hour extracts were made with methylene chloride, the extract evaporated and analysis made of aliquots for the 120, 600 and 3000 ppm dietary levels using high pressure liquid chromatography.

Results: The analytical method was successful in demonstrating near quantitative recovery techniques, but revealed that a homogeneity problem was present in bulk preparation of the animal diet. The homogeneity problem was overcome by switching from the Hobart blender to pre-mixing diet in a Waring blender, thereby achieving target concentration of NP-55 in the feed mix. However, analysis of the diet mixes used throughout the canine feeding studies revealed failure to achieve target doses. (The Hobart mixer was evidently used to prepare the diet for the feeding studies.) (See Tab1e 2 of this report.) Average percent of target dose for the 120 ppm diet varied from 16.0 to 76.5~ of target; for the 600 ppm dose diet, average percent ranged from 77.32 to 87.8% of target and for the 3000 ppm dose diet, the average percent of target dose ranged from 82.7 to 110/2%.

Comments: The non-uniformity of diet dosage, inadequate storage procedures for the administered chemical as well as the method of diet administration (for the latter two see detailed toxicological review - Protocol and comment) have a deleterious effect on the quality of the feeding test protocol and probably affect the results.

	870.3200	21/28-Day Dermal Toxicity  -  Rat

MRID 41987203: In a 21-day dermal toxicity study (MRID 41987203), groups of 5 male and 5 female New Zealand White rabbits were dermally dosed with sethoxydim 6 hours per day over 21 consecutive days at 0 (vehicle control), 40, 200, and 1000 mg/kg/day. The only dose-related dosing site lesion was slight epidermal hyperplasia, which was found in nearly all high-dose males and females, and was probably an adaptive response. There was no evidence of compound-related toxicity on clinical signs, body weights, food consumption, food efficiency, eye health, clinical pathology, organ weights, or gross pathology. The NOAEL is > 1000 mg/kg/day (limit dose) and the systemic LOAEL is not identified.

This study is Acceptable-Guideline, and thus satisfies data requirement 82-2 for a 21-Day
Dermal Toxicity Study. This study received Quality Assurance review.

	870.3465	28-Day Inhalation  -  Rat

MRID 44021202: In a 28-day toxicity study (MRID 44021202), sethoxydim (96.8%; batch no. NS-9212) was administered by inhalation (nose only) to 5 Wistar rats/sex/dose at aerosol analytical concentrations of 0.04, 0.3, and 2.4 mg/L. The control group received filtered air only and the sethoxydim was administered as received from the sponsor. Exposures were 6 hours/day, 5 days/week, for a total of 21 exposures. The mass median aerodynamic diameter (+- geometric standard deviation) for Groups 1, 2, and 3 were 0.8 +- 3.7 um, 1.4 +- 1.8 um, and 1.5 +- 2.4 um, respectively.

No animals died prior to terminal sacrifice. Clinical signs included nasal irritation (bloody crust formation on the nose) in all mid and high-dose rats, salivation during and after exposure in high-dose rats, and fur stained with the test substance at the high dose throughout most or all of the study. Body weights and body weight gains were similar to controls (food consumption was not reported). Clinical chemistry analysis revealed a significant increase in total serum bilirubin high dose males (164% of controls; p<=0.05) and females (239% of controls; p<=0.02), although these levels are not considered to be toxicologically significant. There were no treatment-related findings at necropsy, but microscopic examination showed an increased incidence of slight (grade 2) centrilobular hepatocyte swelling in high-dose males (5/5 vs. 1/5 for controls; p<0.05). The absolute and relative (to terminal body weight) liver weights were increased 14-16% for both sexes (p<=0.05 or 0.01 for females and for relative weight in males). The liver weight increases in both sexes and the microscopic changes in males are general adaptive responses of the liver to a xenobiotic and are not considered adverse effects. A slight increase was also seen in kidney weights of high-dose males (6-8%, NS) and females (12-13%, p<0.05 for absolute weight), but it was unclear if this effect was treatment-related due to a lack of histopathological correlates.

Under the conditions of this one-month study, the LOAEL was 2.4 (651 mg/kg/day) based on increased liver weight, clinical chemistry (increased total serum bilirubin), and liver histopathology. The NOAEL was 0.3 mg/L (81 mg/kg/day), for both male and female rats.

This 28-day study was conducted appropriately and is Acceptable/Non-Guideline.

A.4.2	Prenatal Developmental Toxicity

	870.3700a Prenatal Developmental Toxicity Study - Rat

MRID 43092902: Pregnant CD(R) rats received doses of 0 (vehicle control), 50, 180, 650, and 1000 mg/kg/day by gavage between gestation days 6 and 15. Satellite dams were included in all but the 180 mg/kg/day dose, and the 1000 mg/kg/day group consisted entirely of satellites.  Fetuses carried by satellite dams were not examined. The dams were sacrificed on gestation day 20, and their uteri and ovaries were examined. The fetuses were examined for external, visceral, and skeletal anomalies.

There were no deaths in any group. Clinical signs, seen mostly in the 650 and 1000 mg/kg/day dams, included irregular gait and decreased activity which reversed after several days; and excessive salivation and anogenital staining which did not reverse. Biologically significant decreases in maternal body weights (12-15%, compared to controls) were seen only in the 1000 mg/kg/day satellite group. No compound-related gross lesions were found. The LOAEL for maternal toxicity is 650 mg/kg/day based on irregular gait, decreased activity, excessive salivation, and anogenital staining. The NOAEL for maternal toxicity is 180 mg/kg/day.

There were no resorptions, abortions, premature births, or dead fetuses. The number of corpora lutea, implantation sites, resorptions, and viable fetuses, as well as mean litter sizes and sex ratios were similar for all groups. External and skeletal anomalies, including filamentous tail and lack of tail due to the absence of sacral and/or caudal vertebrae, were dose-related, but visceral anomalies were not. The LOAEL for developmental toxicity is 650 mg/kg/day based on 21-22% decrease in fetal weights, filamentous tail and lack of tail due to the absence of sacral and/or caudal vertebrae, and delayed ossification in the hyoids, vertebral centrum and/or transverse processes, sternebrae and/or metatarsals, and pubes. The NOAEL for developmental toxicity is 180 mg/kg/day.

This study is Acceptable-Guideline, and satisfies the requirement 83-3a for a Developmental Toxicity study in rats. Satellite dams were added at the 650 and 1000 mg/kg/day level "...to clarify maternal effects seen in pilot studies." There was no mention of what these effects were, or what was learned from the satellite animals.

	870.3700b Prenatal Developmental Toxicity Study  -  Rabbit

MRID 43092901: Sethoxydim (96.8% a.i., Lot #NS-9203) was administered in 1% aqueous carboxymethylcellulose to groups of 15 pregnant New Zealand White rabbits by gavage at dose levels of 0, 80, 160, 320 or 400 mg/kg/day from gestation day 6 through 18 (gestation day 0 was the day of mating). Animals were sacrificed on gestation day 30 and uteri were examined for live fetuses and intra-uterine deaths. Fetuses were weighed and examined for external, visceral and skeletal alterations.

Body weight gains were reduced during the dosing period in comparison to control values by 37% for the 400 mg/kg/day dose group without significant differences in group mean body weights. Food consumption values were similarly decrease in the highest dose group (by 10- 25%) during dosing, but were not considered adverse as terminal body weights were not impacted. The LOAEL for maternal toxicity was not observed. The NOAEL for maternal toxicity is 400 mg/kg/day.

There was an apparently dose-related increase in the incidence of incompletely ossified 6[th] sternebrae (1/13, 4/12, 3/15, 6/13 and 9/13 litters in the 0, 80, 160, 320 and 400 mg/kg/day groups, respectively), and the incidence of this variation at the highest dose level was outside the reported historical range (average incidence is 35.1% of litters ranging from 0-57.1%). However, the incidence of all other skeletal ossifications variations was not increased in a dose-related manner. The LOAEL for developmental toxicity is 400 mg/kg/day based on an increase in the incidence of incompletely ossified 6[th] sternebrae. The NOAEL for developmental toxicity is 320 mg/kg/day.

This study is acceptable, guideline and satisfies the requirement for a guideline series §83-3b developmental toxicity study in rabbits.

A.4.3	Reproductive Toxicity

	870.3800 Reproduction and Fertility Effects - Rat

MRID 41510606: In a 2-generation reproduction study (MRID 41510606), NP-55 (sethoxydim technical, 96.86 % a.i., Lot # KK-1240) was administered to 13 male and 26 female/group/dose F0 Charles River CD rats at dose levels of 0, 7.5, 30 or 150 mg/kg/day. The F0 animals produced 2 litters (F1a and F1b). The F1b animals produced 2 litters (F2a and F2b). Clinical signs, body weights, reproductive parameters, necropsy and histopathology data were obtained from parental animals and/or offspring.

There were no indications of systemic toxicity in the F0 parental animals. In the F1 dams in the 150 mg/kg/day group, maternal body weights were slightly decreased during the F2a and F2b gestation and lactation periods (8-10%), with no concomitant effect on food consumption. The 150 mg/kg/day F2b pups had a decrease in body weight of up to -13% by lactation day 21. Malformations were only observed in one F1b (1/240 total pups in litter) and two F2b pups (2/344 total pups in litter). In the F1b litter, cleft palate was observed in one high dose pup. In the F2b litter, one high-dose pup had a thread-like tail, no anal opening, malformed hindlimb, malpositioned kidneys and another high-dose pup had cleft lip, cleft palate and microphthalmia. There were no dose-related gross or microscopic lesions, or developmental variations (cannibalism complicated the evaluation).

Parental Systemic Toxicity NOAEL > 150 mg/kg/day
Parental Systemic Toxicity LOAEL > 150 mg/kg/day

Offspring/Developmental Toxicity NOAEL = 30 mg/kg/day
Offspring/Developmental Toxicity LOAEL =150 mg/kg/day based on decreased pup body weight in F1a, F1b, and F2b during lactation.

Reproductive Toxicity NOAEL > 150 mg/kg/day
Reproductive Toxicity LOAEL > 150 mg/kg/day

The study is Acceptable-Guideline and satisfies the requirement for a guideline series 83-4 Reproduction study in rats. The study is not upgradable. The doses tested were too low to elicit toxicity, and did not approach the limit dose.

The HIARC determined that the Parental Systemic Toxicity NOAEL is > 150 mg/kg/day (HDT) and that the LOAEL could not be established, based on the endpoints of 8-10% decreased in body weight seen at 150 mg/kg/day is not considered adverse (LOEL but not LOAEL is established). The Reproductive Toxicity NOAEL/LOAEL > 150 mg/kg/day (HDT). The Offspring Toxicity NOAEL is 30 mg/kg/day, the LOAEL is 150 mg/kg/day, based on decreased pup body weight of 11-13% in F1a, F1b, and F2b during lactation.

A.4.4	Chronic Toxicity/Carcinogenicity

	870.4300a Chronic Toxicity/Carcinogenicity Study  -  Rat

MRID 43939101: In a chronic toxicity/carcinogenicity study (MRID 43939101), Sethoxydim (96.8% a.i.) was administered to groups of 50 male and 50 female Wistar rats at dietary concentrations of 0, 264, 1000, or 3000 ppm (equivalent to 0, 12, 48, and 143 mg/kg/day for males and 0, 17, 66, and 204 mg/kg/day for females) for up to 24 months (main study groups). Additional groups of 10 rats per sex/per group were fed the same concentrations for up to 24 months for terminal evaluation (satellite groups).

No adverse, treatment-related effects were observed on mortality, clinical signs, hematology, or clinical chemistry.

Body weights were decreased in the 3000 ppm females (main study) during most of the study, becoming most severe between Days 476-644, ranging up to approximately 15% less than controls.  A similar effect was noted in the males, but less severe (not considered adverse).

The liver was the primary target for sethoxydim. Serum total bilirubin levels were increased in the 1000 and 3000 ppm groups by approximately 1.5  -  3.8-fold; however, only the effects at 3000 ppm were considered adverse because of the magnitude of the effect, the consistency across time, and the other adverse effects noted in the liver at this dose.  Eosinophilic foci were noted in the livers in 33/60 (p<0.01) males at 3000 ppm compared with 14/60 controls.  Centrilobular hepatocellular hypertrophy was observed in 38/60 (p<0.01) males at 3000 ppm, 10/60 (p<0.01) males at 1000 ppm, and 33/60 (p<0.01) females at 3000 ppm compared with 0/60 controls of either sex. The hypertrophy at 1000 ppm was not considered adverse in the absence of corroborating evidence of hepatoxicity.  In addition, centrilobular fatty infiltration in the liver was increased in male rats (20/60 vs 7/60 controls, p<0.01) at 3000 ppm.

Treatment-related effects in the lungs included increased incidences of interstitial fibrosis in the 3000 ppm female rats (9/60 vs 2/60 for controls, p<0.05) and heart failure cells in the lungs of 3000 ppm male (16/60 vs 4/60 for controls, p<0.01) and female rats (10/60 vs 3/60, p<0.05).

The LOAEL is 3000 ppm (equivalent to 143 mg/kg/day in males and 204 mg/kg/day in females) based on decreased body weights in females, increased serum total bilirubin in both sexes, increased incidences of eosinophilic foci in livers in males, centrilobular hypertrophy in both sexes, centrilobular fatty infiltration in males, interstitial fibrosis in the lungs in females, and heart failure cells in lungs in both sexes.  The NOAEL was 1000 ppm (equivalent to 48 mg/kg/day in males and 66 mg/kg/day in females).

At the doses tested, there was not a treatment-related increase in tumor incidence when compared to controls.  Dosing was considered adequate based on decreased body weights in females, increased serum total bilirubin in both sexes, and histological lesions in the liver and lung in both sexes.

This study is classified as acceptable, guideline and satisfies the guideline requirements (OPPTS 870.4300; OECD 453) for a combined chronic toxicity/carcinogenicity study in rats.

	870.4300b Chronic Toxicity/Carcinogenicity Study  -  Mouse

MRID 00100527: In a combined chronic toxicity/carcinogenicity study (MRID 00100527) NP-55 (sethoxydim technical, 95.4% a.i., lot # PN-1-2) was administered to 60 BDF1 mice/sex/dose in the diet at concentrations of 40, 120, 360, or 1080 ppm (equivalent to 4.48, 13.77, 41.16, or 134.46 mg/kg bw/day for males and 4.85, 14.86, 44.33, or 142.85 mg/kg bw/day for females) for 24 months. A group of 90 males and 90 females administered the vehicle- (acetone) treated food served as the control. Additional groups of 10/mice/sex/dose were sacrificed at 12 months.

There were no compound-related effects on clinical signs or mortality. The final body weight and body weight gain of male mice in the 1080-ppm group were reduced by 10% and 21%, respectively, compared with the control group. Mean body weights and body weight gains of females were unaffected by treatment. Both absolute and relative liver weights were significantly increased (by 115-138%) at the 24 month sacrifice in males and females in the 1080 ppm group. Increases were also observed in males and females (relative weight only) in this group at the 12-month interim sacrifice. At the 24-month terminal sacrifice, increases in liver weight correlated with clinical chemistry parameters of elevated alanine aminotransferase and aspartate aminotransferase activities and the microscopically-observed lesions including hepatocellular hypertrophy in males in the 1080 ppm group (all p<0.01). Focal granulomatous inflammation, fatty degeneration, and hemosiderin deposition were also observed in the livers of males in the 1080 ppm group (all p<0.01). Fatty degeneration of the liver was present in 87% of males in the 1080 ppm group and 1% of males in the control group. The incidences of fatty degeneration (p<0.05) and hemosiderin deposition (non-significant) in the liver were also elevated in males in the 360 ppm group, although the increased incidences (7-8%) were small compared with incidences (0-1%) in the control group. Only the incidence of fatty degeneration of the liver was significantly elevated in female mice in the 1080 ppm group at 24 months (control, 7%; 1080, 20%; p<0.01).

The LOAEL for NP-55 for systemic toxicity is 360 ppm in the diet (41.2 mg/kg/day) based on early onset of liver effects including hepatocellular hypertrophy and fatty degeneration in male mice. The NOAEL is 120 ppm in the diet (13.8 mg/kg/day).

This chronic/carcinogenicity study in the mouse is Acceptable/Guideline and satisfies the guideline requirement for a chronic/carcinogenicity study OPPTS 870.4300); OECD 453] in mice. Although data on the homogeneity, concentration, and stability of the test material in the diet were not included with the present report, acceptable data are available from related studies.

A.4.5	Neurotoxicity

	870.6200 Subchronic Neurotoxicity Screening Battery

MRID 46846301:  In a subchronic neurotoxicity study (MRID 46845301), Sethoxydim (95.4% a.i., Lot # TM3145] was administered daily to 10 Crl:CD(SD) rats/sex/group in the diet at dose levels of 0, 300, 980, or 3200 ppm (equivalent to 0, 18.4, 59.3, or 206.9 mg/kg bw/day in males, respectively, and 0, 22.2, 72.0, or 234.3 mg/kg bw/day in females, respectively) for 13 weeks.  Neurobehavioral assessment (functional observational battery and motor activity testing) was performed on 10 animals/sex/group during pre-exposure and during Weeks 2, 4, 8, and 13.  Cholinesterase activity was not measured.  At study termination, five animals/sex/group were euthanized and perfused in situ for neuropathological examination.  Of the perfused animals, rats from the control and high-dose groups were subjected to histopathological evaluation of brain and peripheral nervous system tissues.

Effects of treatment were limited to reductions in body weight gain and food consumption at the high dose of 3200 ppm.  In males, body weight gain was transiently reduced over Days 1-8 and 8-15 (76% of controls for both), but was comparable to controls at all other intervals including the overall study interval of Days 1-91 (91% of controls).  In females, body weight gain was reduced over Days 1-8 and 8-15 (61% and 77% of controls, respectively) and for the entire interval of Day 1-91 (79% of controls).  No significant differences in mean absolute body weights were observed in high dose males or females.  Correlating with the reductions in body weight gain were reductions in food consumption in high dose males and females the first two weeks of the study (mean absolute food consumption in males was 92% of controls over Days 8-15 and in females was 85% and 89% of controls over Days 1-8 and 8-15, respectively; mean relative food consumption in females was 87% and 92% of controls, respectively), with high dose females also exhibiting statistically reduced relative food consumption over Days 1-29 (93% of controls).  Mean relative food consumption was statistically increased in high dose males over Days 57-91 (111% of controls), indicating recovery.  No treatment-related adverse effects on body weight or food consumption were noted in males or female rats fed the low- or mid-dose.

No adverse effects of treatment were observed in clinical signs, mortality, ophthalmoscopic findings, FOB parameters, motor activity, brain weights, or during gross or microscopic examination.

The LOAEL for Sprague-Dawley rats was 3200 ppm (equivalent to 206.9 mg/kg bw/day in males and 234.3 mg/kg bw/day in females) based on reduced body weight gain and food consumption, with a NOAEL of 980 ppm (equivalent to 59.3 mg/kg bw/day in males and 72.0 mg/kg bw/day in females).

The study is classified as Acceptable/ Guideline and satisfies the guideline requirement for a subchronic neurotoxicity study in rats (OCSPP 870.6200b; OECD 424).

A.4.6	Metabolism

	870.7485	Metabolism  -  Rat

MRID 00045868: Protocol: Four groups of male and female rats (Fischer strain, Charles River, Japan) aged 9 weeks (groups A, B and D) or 8 weeks (group C) were treated as outlined in Table I to determine the metabolic fate of radioactively labeled technical NP-55. The radioactive sample of NP-55 [(*4-[14]C) - NP-55] was synthesized (Japan Atomic Energy Research Institute) with a specific activity of 10.3 mCi/mM and a radiochemical purity of 98%. Five males and five females from each group selected as representative of the group by uniformity of plasma levels of [l4]C-NP-55 were then individually housed and tested until 95% of the administered radioactive dose was eliminated (48 hours), and then sacrificed. During the 48 hours period, blood, urine and feces were collected for analysis of metabolites and measurement of radioactivity. Blood samples were collected as 0.25, 0.5, 1.0, 2, 3, 4, 6, 12, 24 and 48 hours following treatment. Urine and feces were separately collected on day 1 and 2 from cage apparatus arranged to receive them and during sampling procedures for blood. At 48 hours sacrifice, rats were exsanguinated from the carotid artery, with the plasma separated from blood by centrifugation. Residual bladder urine was pooled with the previously collected 2 day urine sample. Tissues and structures removed weighed and analyzed for metabolites and radioactivity included fat, gonads (testes plus epididymides of males or ovaries of females), spleen, kidney, liver, heart, lung, urinary bladder, femoral muscle and femoral bone. Remaining structures reserved as the carcass were weighed. Radioactivity in samples was measured by liquid scintillation spectrophotometry with external standard, using appropriate methodology for liquid or solid samples. Statistical methods were used to determine means and standard errors for all analytical procedures with the Student's t-test applied to determine differences between 2 groups and a 5% level of significance was adopted.

Results: During the 48 hour test period, all groups showed an average percent of 78.5% administered radioactivity excreted into urine and 20.1% in feces. Less than 2% of the administered radioactive dose was tissue-associated. In the tissues, residual levels of [14]C-NP-55 were highest in liver, with values of 0.6 ppm in groups A, B and C and 13 ppm in group D (the high dose group). The extent of absorption was almost 100% in groups B, C and D, based on radioactivity excreted in urine by group A (intravenous administration considered highest absorption rate). Of remaining tissue-bound [14]C residues, one half remained bound in groups A, B and C and one third in group D (high dose group).

Conclusion: Excretion of NP-55 1n rats in extremely rapid and tissue accumulation is negligible, assuming the DMSO vehicle does not affect excretion or storage of the chemical.

Core Study Category  -  Guidelines

A.5	Calculation of the HED and HEC for Sethoxydim

The methods and dosimetry equations described in EPA's RfC guidance (1994) are suited for calculating HECs based on the inhalation toxicity NOAEL for use in MOE calculations.  The procedure provided in the Office of Pesticide Programs Inhalation Risk Assessment Guidance on the Applications of the RfC Methodology (2014) were followed.

The regional deposited-dose ratio (RDDR), which accounts for the particulate diameter (mass median aerodynamic diameter [MMAD] and geometric standard deviation [g] of aerosols), can be used to estimate the different dose fractions deposited along the respiratory tract.  The RDDR is also based on interspecies differences in ventilation and respiratory-tract surface areas.  Thus, the RDDR can be used to adjust an observed inhalation particulate exposure of an animal to the predicted inhalation exposure for a human.

The RfC methodology applies a dosimetric adjustment that takes into consideration not only the differences in ventilation rate (MV) but also the physicochemical properties of the inhaled compound, the type of toxicity observed (e.g., systemic vs. portal-of-entry) and the pharmacokinetic (PK) (but not pharmacodynamic) differences between animals and humans.  Based on the EPA's RfC guidance (1994), the methodology for RfCs derivation is an estimate of the quantitative dose-response assessment of chronic non-cancer toxicity for individual inhaled chemicals and includes dosimetric adjustment to account for the species-specific relationships of exposure concentration to deposited/delivered dose.  This adjustment is influenced by the physicochemical properties of the inhaled compound as well as the type of toxicity observed (e.g., systemic vs. portal-of-entry), and takes into consideration the PK differences between animals and humans.  Though the RfC methodology was developed to estimate toxicity of inhaled chemicals over a lifetime, it can be used for other inhalation exposures (e.g., acute and short-term exposures) since the dosimetric adjustment incorporates mechanistic determinants of disposition that can be applied to shorter duration of exposures provided the assumptions underlying the methodology are still valid.

Sethoxydim is not volatile in ambient conditions.  The vapor pressure of sethoxydim is only 1.6 x 10[-7] mm Hg at 25 °C.  Sethoxydim would be inhaled as an aerosol.  Calculations used to estimate the inhalation risk to humans from aerosols are dependent on the regional deposited dose ratio (RDDR).  Inhalation studies using aerosols characterize particulate exposure by defining the particulate diameter (mass median aerodynamic diameter [MMAD]) and the geometric standard deviation (σg), which is then used to determine the RDDR.  The RDDR is a multiplicative factor used to adjust an observed inhalation particulate exposure concentration of an animal (A) to the predicted inhalation particulate exposure concentration for a human (H) that would be associated with the same dose delivered to the r[th] region or target tissue.

	RDDRr = (RDDr/Normalizing Factor)A / (RDDr/Normalizing Factor)H

As with calculations for gases, the r regions and potential target tissues are the three respiratory regions (ET, TB, PU).  The RDDR is easily calculated by using a software program designed specifically for computing the RDDR from the MMAD and σg defined from an aerosol inhalation study.  The values for the species-specific parameters used to calculate the RDDR are provided in the EPA document "Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry."

The most sensitive endpoint of toxicity for sethoxydim is hepatotoxicity at 2.4 mg/L, an extrarespiratory effect.  Portal of entry effects were noted as nasal irritation (bloody crust formation on the nose) in all 0.3 and 2.4 mg/L rats (not considered adverse at 0.3 mg/L). The MMAD and GSD reported for the 0.3 mg/L group, as measured by a cascade impactor (from page 27 of the study report), are MMAD = 1.40 and GSD = 1.80.  The resulting RDDR for males and females is 3.105 for extrarespiratory effect.  The body weight value for the RDDR calculation was based on an average of male and female body weights.

Regional Deposited Dose Ratio (RDDR) for Sethoxydim

                       Regional deposited dose ratios

MMAD    =  1.40
Sigma g =  1.80

           Body               Extrathoracic    Tracheobronchial      Pulmonary
SPECIES  weight(g)  VE(ml)    SA(cm^2)   dep   SA(cm^2)   dep    SA(m^2)    dep
--------------------------------------------------------------------------------
    rat      252     181.0    15.000   0.348    22.500   0.073     0.340   0.076
  human    70000   13800.0   200.000   0.245  3200.000   0.062    54.000   0.277
--------------------------------------------------------------------------------
 RATIO     0.004     0.013     0.075   1.422     0.007   1.182     0.006   0.275

 RDDR                              0.249             2.204            0.573

                              Thoracic         Total RT        Extrarespiratory
                              SA(m^2)    dep   SA(m^2)    dep     BW(g)     dep
--------------------------------------------------------------------------------
    rat                        0.342   0.149     0.344   0.497       252   0.497
  human                       54.320   0.125    54.340   0.583     70000   0.583
--------------------------------------------------------------------------------
 RATIO                         0.006   1.190     0.006   0.852     0.004   0.852

 RDDR                              0.917             1.767            3.105

To calculate the HEC and HED, a point of departure (PoD) value of 0.3 mg/L and RDDR of 3.105 were entered into the May 2014 version of the RDDR Excel spreadsheet program.  This program implements the Office of Pesticide Programs Inhalation Risk Assessment Guidance on the Application of the RfC Methodology (February 11, 2014).  Briefly, the following steps are performed: (i) PoD is adjusted for exposure duration using Haber's Law; (ii) the dosimetry adjustment factor (DAF) is derived which compares the minute ventilation rate, deposition fraction for aerosols, and surface area of the affected respiratory tract in the test animal to humans; (iii) the human equivalent concentration (HEC) is estimated as the product of duration-adjusted PoD and the DAF, and (iv) the HEC is converted to the human equivalent dose (HED), with the consideration of volume respired per unit time.  Formulas and a more detailed explanation are provided in the cited document.  The following results were calculated:

Occupational Handler (HEC = 0.699 mg/L)
                                HED (mg/kg/day)
Occupational scenarios assigned a breathing rate of 8.3 L/min
                                    39.762
Occupational scenarios assigned a breathing rate of 16.7 L/min
                                    80.003
Occupational scenarios assigned a breathing rate of 29 L/min
                                    138.927

Residential Handler HEC = 0.932 mg/L and HED = 26.6 mg/kg/day

Appendix B.  International Residue Limits Table

Table B1.  Summary of US and International Tolerances and Maximum Residue Limits for Sethoxydim (121001)
Residue Definition:
US
Canada
Mexico[2]
Codex
40 CFR 180.412:
Plant: sethoxydim: 2-[1-ethoxyimino)butyl]-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen-1-one
(+-)-2-[1-(ethoxyimino)butyl]-5-[2-(ethylthio)propyl]-
3-hydroxy-2-cyclohexen-1-one, including metabolites
containing the cyclohexen-2-one moiety, expressed
as sethoxydim

None
Commodity[1]
Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US
Canada
Mexico[2]
Codex
Fruit, citrus, group 10-10
0.5

Fruit, pome, group 11-10
0.2

Fruit, caneberry, subgroup 13-07A
5.0
5 raspberries

Fruit, bushberry, subgroup 13-07B
4.0
4 aronia berries, buffalo currants, Chilean guavas,  currants, elderberries, European barberries, gooseberries, highbush  (blueberries, cranberries), honeysuckle, huckleberries, jostaberries,  Juneberries (Saskatoon berries), lingonberries, lowbush blueberries, native currants, salal berries, sea buckthorn

Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F
1.0
0.2 amur river grapes, , grapes, hardy kiwifruit, maypop, schisandra berries

4 gooseberries

0.6 raisins

Fruit, low growing berry, except cranberry, subgroup 13-07G
10.0
2 cranberries
4 lowbush blueberries, lingonberries
10 strawberry

Fruit, low growing berry, except strawberry, subgroup 13-07H
2.5
2 cranberries
4 lowbush blueberries, lingonberries

Rapeseed, subgroup 20A
35.0
2.5 borage seeds
0.2 flax seeds
25 rapeseeds (canola)

Sunflower, except safflower, subgroup 20B
7.0
7 sunflower seeds

Cottonseed, subgroup 20C
5.0

Vegetable, bulb, group 3-07
1.0
0.2 onions

Vegetable, fruiting, group 8-10
4.0
2 eggplants
0.5 peppers
4 tomatoes
15 tomato paste

Grass, forage, fodder and hay, group 17, forage
6.0

Grass, forage, fodder and hay, group 17, hay
4.0

Completed: M. Negussie; 11/13/14
[1] Includes only commodities of interest for this action.  Tolerance values should be the HED recommendations and not those proposed by the applicant.
2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

Appendix C.  Metabolites/Degradates

Sethoxydim = MS; 2-[1-(ethoxyimino)butyl]-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen-
1-one

DME = 3-[2-(ethylsulfonyl)propyl]-pentanedioic acid dimethyl ester

DME-OH = 3-[2-(ethylsulfonyl)propyl]-3-hydroxypentanedioic acid dimethyl ester

MSO = sethoxydim sulfoxide; 2-[1-(ethoxyimino)butyl]-5-[2-(ethylsulfinyl)propyl]-3-hydroxy-
2-cyclohexen-1-one

MSO2 = sethoxydim sulfone; 2-[1-(ethoxyimino)butyl]-5-[2-(ethylsulfonyl)propyl]-3-hydroxy-
2-cyclohexen-1-one

M1SO = 2-[1-(imino)butyl]-5-[2-(ethylsulfinyl)propyl]-3-hydroxy-2-cyclohexen-1-one

M2SO = 6-[2-(ethylsulfinyl)propyl]-6,7-dihydro-2-propyl-4(5H)-benzoxazolone

M2SO2 = 6-[2-(ethylsulfonyl)propyl]-6,7-dihydro-2-propyl-4(5H)-benzoxazolone

5-OH-MSO2 = 5-hydroxy sethoxydim sulfone; 2-[1-(ethoxyimino)butyl]-5-[2-
(ethylsulfonyl)propyl]-3,5-dihydroxy-2-cyclohexen-1-one

Appendix D.  Physical/Chemical Properties

Table 2.	Physicochemical Properties of Sethoxydim
Parameter
Value
Reference
Boiling point/range
>130 °C at 6 x 10[-1] mm Hg
HED Chemistry Chapter of the Sethoxydim RED, 6/22/05, W. Donovan
pH
3.95 at 20 °C

Density
1.058 g/cm[3] at 20 °C (specific gravity)

Water solubility
257 ppm at pH 5, 4390 ppm at pH 7 (25 °C)

Solvent solubility
Freely soluble (>10[3] g/100 mL) in organic solvents (methanol, n-octanol, ethyl acetate, n-hexane, toluene, and xylene) at 20 °C

Vapor pressure
1.6 x 10[-7] mm Hg at 25 °C

Dissociation constant, pKa
4.6 at pH 4.5 and 25 °C

Octanol/water partition coefficient, Log(KOW)
KOW = 3.26 x 10[3] at pH 5; 45.1 at pH 7; and 0.93 at pH 9

UV/visible absorption spectrum
Not available

Appendix E.  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 include studies from the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the Agricultural Handler Exposure Task Force (AHETF) database, and the Residential SOPs (lawns and turf).  These data 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.


MEMORANDUM To: 316( b) Phase III NODA Record From: John Sunda, SAIC and Regno Arulgnanendran, Tetra Tech Date: September 12, 2005 Subject: Estimated National Installation Downtime Using Alternative Intake Flows The table below illustrates the assumptions for total weeks of downtime ( weighted values) for each flow option considered.

Net Downtime ( Weeks) for NODA ( weighted) Intake Flow Alternative 50 MGD All 100 MGD Certain Waterbodies 200 MGD All Corrected DIF 55 2 17


[Federal Register Volume 79, Number 96 (Monday, May 19, 2014)]
[Notices]
[Pages 28798-28799]
[FR Doc No: 2014-11106]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

Notice of Opportunity for Public Comment on Release of Federally
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ACTION: Notice.

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SUMMARY: Notice is being given that the FAA is considering a request
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    Issued in College Park, Georgia on May 6, 2014.
Larry F. Clark,
Manager, Atlanta Airports District Office, Southern Region.
[FR Doc. 2014-11106 Filed 5-16-14; 8:45 am]
BILLING CODE 4910-13-P


[Federal Register Volume 79, Number 119 (Friday, June 20, 2014)]
[Notices]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES

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[Docket No. FDA-2004-N-0389]

Agency Information Collection Activities; Submission for Office
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cure, mitigation, or treatment of disease or for growth promotion and
feed efficiency.
    Statutory requirements for cGMPs for Type A medicated articles have
been codified in part 226 (21 CFR part 226). Type A medicated articles
which are not manufactured in accordance with these regulations are
considered adulterated under section 501(a)(2)(B) of the FD&C Act (21
U.S.C. 351(a)(2)(B). Under part 226, a manufacturer is required to
establish, maintain, and retain records for Type A medicated articles,
including records to document procedures required under the
manufacturing process to assure that proper quality control is
maintained. Such records would, for example, contain information
concerning receipt and inventory of drug components, batch production,
laboratory assay results (i.e., batch and stability testing) and
product distribution.
    This information is needed so that FDA can monitor drug usage and
possible misformulation of Type A medicated articles. The information
could also prove useful to FDA in investigating product defects when a
drug is recalled. In addition, FDA will use the cGMP criteria in part
226 to determine whether or not the systems used by manufacturers of
Type A medicated articles are adequate to assure that their medicated
articles meet the requirements of the FD&C Act as to safety and also
meet the article's claimed identity, strength, quality, and purity, as
required by section 501(a)(2)(B) of the FD&C Act. The respondents for
Type A medicated articles are pharmaceutical firms that manufacture
both human and veterinary drugs, those firms that produce only
veterinary drugs, and commercial feed mills.
    In the Federal Register of April 7, 2014 (79 FR 19093), FDA
published a 60-day notice requesting public comment on the proposed
collection of information. No comments were received.
    FDA estimates the burden of this collection of information as
follows:

                               Table 1--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                   Number of
        21 CFR Section             Number of      records per    Total annual    Average burden     Total hours
                                 recordkeepers   recordkeeper       records     per recordkeeper
----------------------------------------------------------------------------------------------------------------
226.42........................              65             260          16,900  0.75 (45                  12,675
                                                                                minutes).
226.58........................              65             260          16,900  1.75............          29,575
226.80........................              65             260          16,900  0.75 (45                  12,675
                                                                                minutes).

226.102.......................              65             260          16,900  1.75............          29,575
226.110.......................              65             260          16,900  0.25 (15                   4,225
                                                                                minutes).
226.115.......................              65              10             650  0.5 (30 minutes)             325
                               ------------------------------------------------                  ---------------
        Total.................  ..............  ..............  ..............  ................          89,050
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection.

    The estimate of time required for record preparation and
maintenance is based on previous Agency communications with industry.
Other information needed to calculate the total burden hours (i.e.,
manufacturing sites, number of Type A medicated articles being
manufactured, etc.) are derived from Agency records and experience.

    Dated: June 16, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-14471 Filed 6-19-14; 8:45 am]
BILLING CODE 4160-01-P


[Federal Register: August 3, 2007 (Volume 72, Number 149)]
[Rules and Regulations]
[Page 43169-43172]
[DOCID:fr03au07-11]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 52

[EPA-R05-OAR-2006-0541; FRL-8449-6]

Approval and Promulgation of Air Quality Implementation Plans;
Michigan

AGENCY: Environmental Protection Agency (EPA).

ACTION: Direct final rule.

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

SUMMARY: EPA is approving a request submitted by the Michigan
Department of Environmental Management (MDEQ) on March 31, 2006, to
revise the Michigan State Implementation Plan (SIP) to amend R336.1627
and R336.2005, and adopt R336.2004. These changes take place within
Part 6, Emission Limitations and Prohibitions--Existing Sources of
Volatile Organic Compound Emissions; Delivery Vessels; Vapor Collection
Systems; and Part 10, Intermittent Testing and Sampling, respectively.

DATES: This rule is effective on October 2, 2007, unless EPA receives
adverse written comments by September 4, 2007. If EPA receives adverse
comments, EPA will publish a timely withdrawal of the rule in the
Federal Register and inform the public that the rule will not take
effect.

ADDRESSES: Submit your comments, identified by Docket ID No. EPA-R05-
OAR-2006-0541 by one of the following methods:
    1. http://www.regulations.gov: Follow the on-line instructions for

submitting comments.
    2. E-mail<EMAIL_ADDRESS>    3. Fax:<PHONE_NUMBER>.
    4. Mail: John M. Mooney, Chief, Criteria Pollutant Section, Air
Programs Branch (AR-18J), U.S. Environmental Protection Agency, 77 West
Jackson Boulevard, Chicago, Illinois 60604.
    5. Hand Delivery: John M. Mooney, Chief, Criteria Pollutant
Section, Air Programs Branch (AR-18J), U.S. Environmental Protection
Agency, 77 West Jackson Boulevard, Chicago, Illinois 60604. Such
deliveries are only accepted during the Regional Office normal hours of
operation, and special arrangements should be made for deliveries of
boxed information. The Regional Office official hours of business are
Monday through Friday, 8:30 a.m. to 4:30 p.m. excluding Federal
holidays.
    Instructions: Direct your comments to Docket ID No. EPA-R05-OAR-
2006-0541. EPA's policy is that all comments received will be included
in the public docket without change and may be made available online at
http://www.regulations.gov, including any personal information

provided, unless the comment includes information claimed to be
Confidential Business Information (CBI) or other information whose
disclosure is restricted by statute. Do not submit information that you
consider to be CBI or otherwise protected through http://www.regulations.gov or e-mail. The http://www.regulations.gov Web site

is an ``anonymous access'' system, which means EPA will not know your
identity or contact information unless you provide it in the body of
your comment. If you send an e-mail comment directly to EPA without
going through http://www.regulations.gov, your e-mail address will be

automatically captured and included as part of the comment that is
placed in the public docket and made available on the Internet. If you
submit an electronic comment, EPA recommends that you include your

name and other contact information in the body of your comment and with
any disk or CD-ROM you submit. If EPA cannot read your comment due to
technical difficulties and cannot contact you for clarification, EPA
may not be able to consider your comment. Electronic files should avoid
the use of special characters, any form of encryption, and be free of
any defects or viruses. For additional instructions on submitting
comments, go to Section I of the SUPPLEMENTARY INFORMATION section of
this document.
    Docket: All documents in the docket are listed in the http://www.regulations.gov
 index. Although listed in the index, some

information is not publicly available, e.g., CBI or other information
whose disclosure is restricted by statute. Certain other material, such
as copyrighted material, will be publicly available only in hard copy.
Publicly available docket materials are available either electronically
in http://www.regulations.gov or in hard copy at the Environmental

Protection Agency, Region 5, Air and Radiation Division, 77 West
Jackson Boulevard, Chicago, Illinois 60604. This Facility is open from
8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal
holidays. We recommend that you telephone Jonathan Nichols, Life
Scientist, at<PHONE_NUMBER> before visiting the Region 5 office.

FOR FURTHER INFORMATION CONTACT: Jonathan Nichols, Life Scientist,
Criteria Pollutant Section, Air Programs Branch (AR-18J), Environmental
Protection Agency, Region 5, 77 West Jackson Boulevard, Chicago,
Illinois 60604,<PHONE_NUMBER><EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: Throughout this document whenever ``we,''
``us,'' or ``our'' is used, we mean EPA. This supplementary information
section is arranged as follows:

I. Background
    A. When did the State submit the requested rule revisions to
EPA?
    B. Did Michigan hold public hearings for each of these rule
revisions?
II. What are the revisions that the State requests be incorporated
into the SIP?
    A. Part 6--Emission Limitations for Existing Sources
    B. Part 10--Changes to Intermittent Testing and Sampling
III. What is EPA's evaluation of the rule?
IV. Statutory and Executive Order Reviews

I. Background

A. When did the State submit the requested rule revisions to EPA?

    MDEQ submitted the requested rule revisions on March 31, 2006.

B. Did Michigan hold public hearings for each of these rule revisions?

    MDEQ held a public hearing for the rule revisions on October 31,
2005, and did not receive any adverse comments.

II. What are the revisions that the State requests be incorporated into
the SIP?

    The State has requested the following revisions: Changes to Part 6,
Emission Limitations and Prohibitions--Existing Sources of Volatile
Organic Compound Emissions; and changes to Part 10, Intermittent
Testing and Sampling. The revisions are described in more detail below.

A. Part 6--Emission Limitations for Existing Sources

    MDEQ is requesting the amendment of Part 6, R336.1627, in order to
replace the MDEQ Vapor Tightness Test (VTT) method with EPA Method 27.
The MDEQ VTT method is not an acceptable substitution for the leak test
required by the U.S. Department of Transportation (U.S. DOT).
Therefore, tank trucks must undergo VTT using both state and federal
test methods. As written, EPA Method 27 is more stringent than the leak
test required by MDEQ, satisfying both U.S. DOT and MDEQ standards.
    In addition, MDEQ is requesting an amendment to test submittal
requirements in order to provide consistency between U.S DOT and MDEQ
requirements with regard to the time period within which tank trucks
must be tested. The amendment would require delivery vessels to perform
the VTT within one year of the date of the previous test, rather than
the existing, narrow time period of April 1 to June 30. Under the
amendment, the results of the test would be submitted to MDEQ within 30
days of test completion. Upon successful completion of the required
testing, the vessel would be deemed provisionally certified providing
the department does not invalidate the certification by issuing
disapproval within 45 days of receipt of the results.

B. Part 10--Changes to Intermittent Testing and Sampling

    MDEQ is requesting the amendment of Part 10, Intermittent Testing
and Sampling, to incorporate Method 27 by reference at R336.2004, and
to amend R336.2005, the reference test method used to detect gasoline
vapor leaks by a combustible gas detector. The amendment to R336.2005
removes the VTT component, but leaves the reference test method to
detect gasoline vapor leaks by a combustible gas detector intact.
Method 27, which is more stringent than the existing state VTT method,
is incorporated in R336.2004.

III. What is EPA's evaluation of the rule?

    We are approving revisions to the Michigan SIP in two areas: (1) To
amend R336.1627 of Part 6, Emission Limitations and Prohibitions--
Existing Sources of Volatile Organic Compound Emissions; Delivery
Vessels; Vapor Collection Systems, by replacing the MDEQ VTT method
with EPA Method 27, and to adopt the U.S. DOT annual VTT requirement
and test submittal requirements; and, (2) to amend Part 10,
Intermittent Testing and Sampling, through incorporating Method 27 by
reference at R336.2004, and to amend R336.2005, the reference test
method used to detect gasoline vapor leaks by a combustible gas
detector.
    The main revisions to R336.1627 are the replacement of its VTT test
with Method 27 and the requirement to test the delivery vessel within
one year of the previous test. Both of these revisions are consistent
with EPA guidance. In addition, the following factors add to the
effectiveness of this rule: (1) the testing stations are certified by
the Michigan Department of Transportation and the tests that are
performed at these stations are spot checked by the MDEQ; (2) the MDEQ
has a history of reviewing all test results, and rejects those that are
inadequate, within 30 days; and, (3) the Michigan gasoline terminals do
not accept any tank trucks that are not certified to be in compliance
with R336.1627, and are prohibited from accepting uncertified trucks
due to the emission limitations found in 40 CFR part 60, subpart XX,
which cover the same sources through limits on loading racks at bulk
liquid gasoline terminals constructed or modified after December 17,
1980, that deliver liquid product into gasoline tank trucks. These
regulations require that a gasoline terminal owner or operator not
reload gasoline delivery vessels without documentation indicating that
a VTT has been performed.
    Michigan rule R336.1627 provides that the vessel is deemed to have
passed the gasoline vapor leak detection test if Michigan does not
notify the owner or operator of the vessel of the vessel's failure to
pass the test within 45 days. EPA strongly discourages the use of
default approvals. However, we find this rule to be approvable due to
the special circumstances described above and also because
recertification is required within a year. Nevertheless, should
Michigan revise its rules to remove the safeguards described above,

EPA will require the State to revise this section of the SIP.
    We are publishing this action without prior proposal because we
view this as a noncontroversial amendment and anticipate no adverse
comments. However, in the proposed rules section of this Federal
Register publication, we are publishing a separate document that will
serve as the proposal to approve the state plan if relevant adverse
written comments are filed. This rule will be effective October 2, 2007
without further notice unless we receive relevant adverse written
comments by September 4, 2007. If we receive such comments, we will
withdraw this action before the effective date by publishing a
subsequent document that will withdraw the final action. All public
comments received will then be addressed in a subsequent final rule
based on the proposed action. The EPA will not institute a second
comment period. Any parties interested in commenting on this action
should do so at this time. If we do not receive any comments, this
action will be effective October 2, 2007.

IV. Statutory and Executive Order Reviews

Executive Order 12866: Regulatory Planning and Review

    Under Executive Order 12866 (58 FR 51735, October 4, 1993), this
action is not a ``significant regulatory action'' and, therefore, is
not subject to review by the Office of Management and Budget.

Executive Order 13211: Actions That Significantly Affect Energy Supply,
Distribution, or Use

    Because it is not a ``significant regulatory action'' under
Executive Order 12866 or a ``significant energy action,'' this action
is also not subject to Executive Order 13211, ``Actions Concerning
Regulations That Significantly Affect Energy Supply, Distribution, or
Use'' (66 FR 28355, May 22, 2001).

Regulatory Flexibility Act

    This action merely approves state law as meeting Federal
requirements and imposes no additional requirements beyond those
imposed by state law. Accordingly, the Administrator certifies that
this rule will not have a significant economic impact on a substantial
number of small entities under the Regulatory Flexibility Act (5 U.S.C.
601 et seq.).

Unfunded Mandates Reform Act

    Because this rule approves pre-existing requirements under state
law and does not impose any additional enforceable duty beyond that
required by state law, it does not contain any unfunded mandate or
significantly or uniquely affect small governments, as described in the
Unfunded Mandates Reform Act of 1995 (Pub. L. 104-4).

Executive Order 13175: Consultation and Coordination With Indian Tribal
Governments

    This rule also does not have tribal implications because it will
not have a substantial direct effect on one or more Indian tribes, on
the relationship between the Federal Government and Indian tribes, or
on the distribution of power and responsibilities between the Federal
Government and Indian tribes, as specified by Executive Order 13175 (59
FR 22951, November 9, 2000).

Executive Order 13132: Federalism

    This action also does not have Federalism implications because it
does not have substantial direct effects on the states, on the
relationship between the national government and the states, or on the
distribution of power and responsibilities among the various levels of
government, as specified in Executive Order 13132 (64 FR 43255, August
10, 1999). This action merely approves a state rule implementing a
Federal standard, and does not alter the relationship or the
distribution of power and responsibilities established in the Clean Air
Act.

Executive Order 13045: Protection of Children From Environmental Health
and Safety Risks

    This rule also is not subject to Executive Order 13045 ``Protection
of Children from Environmental Health Risks and Safety Risks'' (62 FR
19885, April 23, 1997), because it approves a state rule implementing a
Federal Standard.

National Technology Transfer Advancement Act

    In reviewing SIP submissions, EPA's role is to approve state
choices, provided that they meet the criteria of the Clean Air Act. In
this context, in the absence of a prior existing requirement for the
state to use voluntary consensus standards (VCS), EPA has no authority
to disapprove a SIP submission for failure to use VCS. It would thus be
inconsistent with applicable law for EPA, when it reviews a SIP
submission, to use VCS in place of a SIP submission that otherwise
satisfies the provisions of the Clean Air Act. Thus, the requirements
of section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (15 U.S.C. 272 note) do not apply.

Paperwork Reduction Act

    This rule does not impose an information collection burden under
the provisions of the Paperwork Reduction Act of 1995 (44 U.S.C. 3501
et seq.).

Congressional Review Act

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit a report containing this rule and other
required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication of the rule in the Federal Register. A major rule cannot
take effect until 60 days after it is published in the Federal
Register. This action is not a ``major rule'' as defined by 5 U.S.C.
804(2).
    Under section 307(b)(1) of the Clean Air Act, petitions for
judicial review of this action must be filed in the United States Court
of Appeals for the appropriate circuit by October 2, 2007. Filing a
petition for reconsideration by the Administrator of this final rule
does not affect the finality of this rule for the purposes of judicial
review nor does it extend the time within which a petition for judicial
review may be filed, and shall not postpone the effectiveness of such
rule or action. This action may not be challenged later in proceedings
to enforce its requirements. (See section 307(b)(2).)

List of Subjects in 40 CFR Part 52

    Environmental protection, Air pollution control, Carbon monoxide,
Incorporation by reference, Intergovernmental relations, Lead, Nitrogen
dioxide, Ozone, Particulate matter, Reporting and recordkeeping
requirements, Sulfur oxides, Volatile organic compounds.

    Dated: July 24, 2007.
Walter W. Kovalick Jr.,
Acting Regional Administrator, Region 5.

0
40 CFR part 52 is amended as follows:

PART 52--[AMENDED]

0
1. The authority citation for part 52 continues to read as follows:

    Authority: 42 U.S.C. 7401 et seq.

Subpart X--Michigan

0
2. In Sec.  52.1170(c) the table is amended as follows:
0
a. Under Part 6 by revising entry ``R336.1627''.
0
b. Under Part 10 by revising entries ``R336.2004'' and ``R336.2005''.

Sec.  52.1170  Identification of plan.

* * * * *
    (c) * * *

                                                            EPA-Approved Michigan Regulations
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                       State
         Michigan citation                       Title               effective            EPA approval date                        Comments
                                                                        date
--------------------------------------------------------------------------------------------------------------------------------------------------------

                                                                      * * * * * * *
--------------------------------------------------------------------------------------------------------------------------------------------------------
                         Part 6. Emission Limitations and Prohibitions--Existing Sources of Volatile Organic Compound Emissions
--------------------------------------------------------------------------------------------------------------------------------------------------------

                                                                      * * * * * * *
R336.1627..........................  Delivery Vessels; Vapor            2/22/06  8/3/07, [Insert page number where
                                      Collection Systems.                         the document begins].

                                                                      * * * * * * *
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                       Part 10. Intermittent Testing and Sampling
--------------------------------------------------------------------------------------------------------------------------------------------------------

                                                                      * * * * * * *
R336.2004..........................  Appendix A; reference test         2/22/06  8/3/07, [Insert page number where
                                      methods; adoption of federal                the document begins].
                                      reference test methods.
R336.2005..........................  Reference test methods for         2/22/06  8/3/07, [Insert page number where
                                      state-requested tests of                    the document begins].
                                      delivery vessels.

                                                                      * * * * * * *
--------------------------------------------------------------------------------------------------------------------------------------------------------

* * * * *
[FR Doc. E7-15011 Filed 8-2-07; 8:45 am]

BILLING CODE 6560-50-P