Developmental toxicity: There were no treatment related effects on litter cesarean parameters, nor on the incidence of fetal variations or malformations. The developmental toxicity NOAEL is 190 mg/ kg bw/ day. A developmental toxicity LOAEL was not established in this study (> 190 mg/ kg bw/ day).

The developmental toxicity study in the rabbit is classified Acceptable ( guideline) and satisfies the guideline requirement for a developmental toxicity study ( OPPTS 870.3700; OECD 414) in the rabbit ( nonrodent).

( 2) In an oral developmental toxicity study ( MRIDs 41592006, 42054901 and 42077101), acetochlor ( technical, 90.5% a. i., lot # P2) was administered to 16 female New Zealand White rabbits/ dose by gavage in corn oil vehicle ( dosing volume of 1 mL/ kg) at dose levels of 0, 30, 100 or 300 mg/ kg bw/ day from days 6 through 18 of gestation.

Maternal toxicity: There were no effects of treatment observed on maternal survival, clinical signs of toxicity, body weight or weight gain, food consumption or cesarean parameters. Although no toxicity was observed in this study, the results of the range finding study ( MRID 42077101) indicated that toxicity ( body weight decrement) was observed between 200 400 mg/ kg bw/ day and therefore that a LOAEL was approached in the main study; dose selection was therefore determined to be appropriate. The maternal toxicity NOAEL is 300 mg/ kg bw/ day ( highest dose tested). A maternal LOAEL was not established in this study but was likely approached, based on the results of the range finding study.

Developmental toxicity: There were no effects of treatment observed on cesarean parameters and no effect on the incidence of fetal variations or malformations. The developmental NOAEL is 300 mg/ kg bw/ day ( highest dose tested). A developmental LOAEL was not established in this study.

The developmental toxicity study in the rabbit is classified Acceptable/ guideline and satisfies the guideline requirement for a developmental toxicity study ( OPPTS 870.3700; OECD 414) in the rabbit. Although a maternal toxicity LOAEL was not achieved, dosing is considered adequate based on the results of the range finding study ( see above). In addition, a second acceptable developmental toxicity study in the rabbit is available ( MRID 40134101) which showed weight loss during treatment at 190 mg/ kg bw/ day. Page 51 of 118 4.2.4 Reproductive Toxicity Study Three two generation reproductive toxicity studies in the rat have been submitted for acetochlor.

( 1) In a two generation reproduction study ( MRID 00131391), MON 097 ( acetochlor tech., 94.2% a. i., lot # 1992024) was continuously administered to 24 female and 12 male Charles River albino rats/ dose in the diet at dose levels of 0, 500, 1500 or 5000 ppm ( equivalent to average daily intakes during premating in F0 animals of 0, 30.8, 60.4 or 316 mg/ kg bw/ day, males and 0, 46.2, 130.4 or 442 mg/ kg bw/ day, females and in F1 animals of 0, 29.9, 87.8 or 333 mg/ kg/ day, males and 43.6, 129.8 or 441 mg/ kg/ day, females). Mating was initiated after at least 100 days of treatment for the F0 parental animals and at least 120 days of treatment for the F1 parental animals. Matings were performed twice for each generation. Five F1b and F2b pups/ sex/ dose and ten F1 parents/ sex/ dose were also selected for evaluation of testes, ovary, pituitary, thyroid, spleen and liver weights and histopathology.

Parental toxicity: At 1500 ppm, mean parental premating body weights were slightly reduced compared to controls. At the end of the premating periods ( about Study Week 14), F0 parental male and female weights were reduced by  6.8% ( p< 0.01) and  4.3% ( NS) compared to controls, respectively, with gains decreased by  9 to  10%. F1 parental male and female weights were reduced by  7.2% ( NS) and  8.3% ( p< 0.01) by the end of premating ( about Study Week 51), with gains reduced by 6.4% in males and 9.4% in females. Mean maternal gestational body weights were reduced among all maternal parental groups except for the F2a dams ( average decrease during gestation was about  13% less than controls). Adjusted maternal body weights were not provided in this study. At 5000 ppm, mean parental body weights were reduced compared to controls for all groups. The mean weights of F0 males and females were significantly lower by the end of premating at Week 14 ( 11% and  20%, respectively; weight gain  16% and  20% less, respectively), as well as at Week 34 ( 10% and  25%, respectively; weight gains  14% and  41% less, respectively). F1 males and females had significantly lower body weights at the start of premating ( Week 33, males  39% and females  34%), but weights during the study continued to be lower than controls: by the end of premating ( about Week 51, males were reduced by  23% in males ( gain  20%) and  26% in females ( gain  43%). At week 74 ( end of study), body weights of males were  19% below controls ( gain  13%) and female weights were  33% below controls ( gain  51%). Mean maternal gestational body weights were lower for all parental mating groups ( an average of  34% below controls). Slight reductions (< 10%) in food consumption were also reported. Some increases in absolute/ relative organ weights were observed in F1 parents ( e. g., thyroid, liver, kidney). The incidence of chronic nephritis was increased in F1 females ( 8/ 10 vs. 0/ 10 examined). F0 animals were not evaluated for organ weights except testes in males, which showed no effects. There were no treatment related effects on survival or clinical signs of toxicity. The parental systemic LOAEL is 1500 ppm ( 60.4 mg/ kg bw/ day in males, 130.4 mg/ kg bw/ day in females), based on reduced body weight/ weight gain during premating in both generations. The parental systemic NOAEL is 500 ppm ( 30.8 mg/ kg bw/ day in males, 46.2 mg/ kg bw/ day in females).

Offspring toxicity: At 1500 ppm, mean pup body weights on Lactation Day 21 showed a slight Page 52 of 118 decrease in the F2a and F2b offspring ( 7 to  13% below controls, statistically significant only for F2b males). At 5000 ppm, mean pup body weights on Lactation Day 21 in all F1 and F2 pup groups were reduced ( about  42% less than controls) and mean litter size tended to be smaller ( grand mean for all generations: at high dose 9.9 vs. 12.3, 13.0 and 11.8 at control, low and mid dose; statistical significance only achieved for the F1b generation). Although statistically significantly increased abs/ rel thyroid weights were reported at low and mid dose, they were not considered to be a clear treatment related finding based on lack of a dose response and lack of a corresponding increase in liver weights. No effects on pup survival, birth weight, gross abnormalities or other cesarean offspring parameter were observed. The offspring LOAEL is 1500 ppm ( 60.4 mg/ kg bw/ day, males; 130.4 mg/ kg bw/ day), based on slightly reduced pup body weight during lactation in F2 offspring. The offspring NOAEL is 500 ppm ( 30.8 mg/ kg bw/ day, males; 46.2 mg/ kg bw/ day).

Reproductive toxicity: There was no evidence of reproductive toxicity observed at any dose tested in this study. The reproductive NOAEL is 5000 ppm ( 324.5 mg/ kg bw/ day in males, 441.5 mg/ kg bw/ day in females). A reproductive toxicity LOAEL was not determined in this study.

This study is classified Acceptable/ guideline and satisfies the guideline requirement for a 2 generation reproductive study ( OPPTS 870.3800); OECD 416 in the rat.

( 2) In a two generation reproduction study ( MRID 41565120), SC 5676 ( acetochlor tech., 90.8% a. i., batch/ lot # 1 and 3) was administered to 25 Sprague Dawley CD rats/ sex/ dose in the diet at dose levels of 0, 18, 175 or 1750 ppm ( equivalent to average daily premating intakes for the F0 generation of 0, 1.27, 12.6 or 123.8 mg/ kg/ day, F0 males and 0, 1.63, 15.5 or 157.4 mg/ kg/ day, F0 females; 0, 0, 1.53, 15.2 or 152.1 mg/ kg bw/ day, F1 males and 1.83, 18.3 or 192.4 mg/ kg bw/ day, F1 females). Matings were performed twice for each generation.

Parental toxicity: At 1750 ppm, mean body weights were significantly lower by the end of premating in all parental animals ( F0 males and females  5% and  6% below controls, respectively, at Week 8; F1 males and females  11% and  12% below controls, respectively, at the end of Week 13). Premating mean body weight gain of parental animals was also lower than controls ( 10% and  18%, F0 males and females, respectively, and  12% and  14%, F1 males and females, respectively), and slight reductions (< 10%) in food consumption were reported. Some increases in absolute/ relative organ weights were observed ( e. g., liver, kidney) but were not accompanied by microscopic findings. There were no treatment related effects on survival, clinical signs of toxicity or gross/ microscopic pathology ( microscopic examination included evaluation of nasal turbinates). The parental systemic LOAEL is 1750 ppm ( 123.8 mg/ kg bw/ day in males, 157.4 mg/ kg bw/ day in females), based on reduced body weight/ weight gain during premating in both generations. The parental systemic NOAEL is 175 ppm ( 12.6 mg/ kg bw/ day in males, 15.5 mg/ kg bw/ day in females).

Offspring toxicity: At 1750 ppm, mean pup body weights were reduced on lactation Day 21 ( 17% Page 53 of 118 and 9% in F1a and F1b pups, respectively; 23% and 16% in F2a and F2b pups, respectively; p< 0.01 except F1b pups NS). No effects on pup survival, birth weight, gross abnormalities or other offspring parameters were observed. The offspring LOAEL is 1750 ppm ( 123.8 mg/ kg bw/ day, males; 157.4 mg/ kg bw/ day, females), based on reduced pup body weight during lactation. The offspring NOAEL is 175 ppm ( 12.6 mg/ kg bw/ day, males; 15.5 mg/ kg bw/ day, females.

Reproductive toxicity: There was no evidence of reproductive toxicity observed at any dose tested in this study. The reproductive NOAEL is 1750 ppm ( 123.8 mg/ kg bw/ day in males, 157.4 mg/ kg bw/ day in females). A reproductive toxicity LOAEL was not determined in this study.

This study is classified Acceptable/ guideline and satisfies the guideline requirement for a 2 generation reproductive study ( OPPTS 870.3800); OECD 416 in the rat.

( 3) In a 2 generation reproduction toxicity study, acetochlor was administered continuously in the diet to CD ( SD) IGS BR ( Sprague Dawley) rats ( 26/ sex/ dose) at nominal dose levels of 0, 200, 600, or 1750 ppm ( equivalent to 0, 21.2, 65.6, and 196.4 mg/ kg/ day in F1 males and 0, 22.4, 70.9, and 215.9 mg/ kg/ day in F1 females). F0 animals were given test article diet formulations for 10 weeks prior to mating to produce the F1 litters. On postnatal day ( PND) 29, F1 animals ( 26/ sex/ dose) were selected to become the F1 parents of the F2 generation and were given the same concentration test formulation as their dams. F1 animals were given test formulations for 10 weeks prior to mating to produce the F2 litters. Dietary administration of the test material to all animals was continuous throughout the study. The analytical data indicated that the mixing procedure was adequate and that variability was within acceptable ranges.

Parental toxicity and tumorigenicity: No treatment related clinical observations were observed in this study. Survival of parental animals was unaffected by treatment at any dose level. Mean premating body weight, body weight gain, and food consumption were consistently and statistically significantly reduced in both F0 and F1 animals at the high dose level ( 1750 ppm). In addition, mean body weight and body weight gain were reduced in F0 and F1 dams during early gestation and lactation at the high dose level, often coinciding with decreased food consumption. No effects of treatment were observed at 600 and 200 ppm. At 1750 ppm, relative kidney, liver, and thyroid weights were significantly increased for F0 and F1 parental males and females, and relative ovarian weights were decreased for F0 and F1 females as compared to controls. Increased relative liver and thyroid weights were also observed at 600 ppm. However, there were no gross or histopathological changes in these tissues that appeared to be associated with treatment.

Histopathological evaluation revealed treatment related incidences of benign prolferative lesions ( focal epithelial hyperplasia and polypoid adenomata) in the epithelial lining of the ethmoid region of the nasal cavity in F0 and F1 adult animals receiving 1750 ppm acetochlor and in F1 animals at the 600 ppm level. Although no clear evidence of malignant change was apparent, the animals were just over 4 months of age and had been exposed to acetochlor for approximately 18 weeks ( F0) or 25 weeks ( F1) when these lesions were observed. Minimally increased brown pigment ( lipofuscin) was observed in the olfactory mucosa, mainly in the lamina propria and occasionally in the basal Page 54 of 118 epithelium in most animals receiving 600 and 1750 ppm in both F0 and F1 generations and also in F1 females at the 200 ppm dose level; however, this finding was not considered to be of toxicological significance. The parental LOAEL is 600 ppm ( 65.6 mg/ kg/ day in F1 males; 70.9 mg/ kg/ day in F1 females), based on focal hyperplasia and polypoid adenomata in the nasal epithelium of adult F1 offspring at study termination. The parental NOAEL is 200 ppm ( 21.2 mg/ kg/ day in F1 males; 22.4 mg/ kg/ day in F1 females).

Offspring toxicity: A significant treatment related decrease in the number of implantations was observed at 1750 ppm in both the F0 and F1 generations. In addition, the mean number of live pups on postnatal day 1 decreased in a dose related manner in both the F1 and F2 litters. Mean live F1 pups per litter was significantly decreased at 1750 ppm, and the mean number of live plus dead pups per litter was statistically significantly lower in F1 and F2 litters at 1750 ppm and also in F2 litters at 600 ppm. These findings are considered possible evidence of fetal loss. Postnatal survival was not affected by treatment. Initial mean body weights of F1 pups of both sexes were significantly decreased in both the 600 and 1750 ppm groups. At the 1750 ppm level, significantly decreased mean F1 pup body weights were also observed in late lactation and overall body weight gain was significantly reduced as compared to controls. In F2 litters, male and female pup body weights were reduced in both 1750 and 600 ppm dose levels from mid to late lactation, and overall F2 pup weight gain was reduced. A decrease in anogenital distance in F2 males on PND 1, and a 3 day treatment related delay in the day of vaginal opening in F1 females at the high dose level appeared to be associated with delayed growth. Decreases in absolute mean brain weights of F1 males and F2 males and females were noted at 1750 ppm. On a relative to body weight basis, ratios were statistically increased for the brain in F2 pups at the 600 ppm dose as well. Mean absolute spleen weights were also decreased in F1 males and in both sexes of the F2 pups at both the mid and high dose levels. They were also reduced on a relative basis in 600 ppm F2 females. Mean absolute thymus weights were also decreased in F2 pups at the high dose level, but not relative to body weight. No macroscopic changes were reported. The offspring LOAEL is 600 ppm ( 65.6 mg/ kg/ day in F1 males; 70.9 mg/ kg/ day in F1 females), based on decreased F2 litter size at birth, decreased F1 and F2 pup body weights during lactation, and decreased absolute and relative spleen weights in F2 weanlings; and on the presence of focal hyperplasia and polypoid adenomata in the nasal epithelium of adult F1 offspring at study termination. The offspring NOAEL is 200 ppm ( 21.2 mg/ kg/ day in F1 males; 22.4 mg/ kg/ day in F1 females).

Reproductive toxicity: The number of implantations decreased in a dose related manner in both the F0 and F1 generations, the differences reaching statistical significance at the high dose level in both generations. In addition, the mean number of live pups on postnatal day 1 decreased in a dose related manner in both the F0 and F1 litters. Due to the lack of corpora lutea count data, the origin of the decreased implantation counts could not be determined; therefore, this was conservatively interpreted as a possible effect on reproduction. The LOAEL for reproductive toxicity is 1750 ppm ( 196.4 mg/ kg/ day in F1 males; 215.9 mg/ kg/ day in F1 females), based on decreased number of implantations. The reproductive toxicity NOAEL is 600 ppm ( 65.6 mg/ kg/ day in F1 males; 70.9 mg/ kg/ day in F1 females). Page 55 of 118 This study is Acceptable/ Guideline ( 870.3800) and satisfies the requirements for a two generation reproduction and fertility effects study in rats. Several deficiencies have been identified, but do not compromise the interpretation of the study. These include: the lack of reproductive and viability indices and the absence of historical control pathology incidence data. These data should be submitted as confirmatory.

4.2.5 Additional Information from Literature Sources No additional information pertinent to FQPA considerations was identified.

4.2.6 Pre and/ or Postnatal Toxicity <IP_ADDRESS> Determination of Susceptibility The available developmental toxicity studies in two species do not show evidence of increased susceptibility of the offspring. No evidence of increased susceptibility was observed in three twogeneration reproductive toxicity studies in the rat. Toxicity to offspring was observed at or above maternally toxic dose levels.

<IP_ADDRESS> Degree of Concern Analysis and Residual Uncertainties for Pre and/ or Post natal Susceptibility Concern for increased susceptibility is low since toxicity to offspring was observed only at maternally toxic doses in developmental toxicity studies in the rat and rabbit and three multigeneration reproductive toxicity studies in the rat. Clear NOAELs for offspring and adults were observed in all of the studies.

4.3 Recommendation for a Developmental Neurotoxicity Study 4.3.1 Evidence that supports requiring a Developmental Neurotoxicity study Acetochlor has shown neurotoxic potential in several studies in more than one species ( see summary above in Section 4.2.2). Pre and/ or post natal sensitivity for neurotoxic effects of acetochlor is not known. The HED HIARC ( HED TXR# 013858, meeting of May 27, 1999) recommended that a developmental neurotoxicity study be submitted, based on these neurotoxicity findings. Since that time, the rat acute and subchronic neurotoxicity studies have been submitted. Results of the acute neurotoxicity study show a LOAEL of 500 mg/ kg ( single gavage dose) based on decreased motor activity in females ( NOAEL of 150 mg/ kg) and clinical signs of toxicity including hunched posture, piloerection and staining around the mouth; in single animals, decreased activity, chromodacryorrhea, hypothermia, labored breathing, sides pinched in and upward curvature of the spine were reported. In the subchronic rat neurotoxicity study, transiently decreased hindlimb grip strength ( only at week 2) was observed in males, but not females, also at the highest dose tested of 139 mg/ kg/ day. The two developmental toxicity studies in rats  both dosing pregnant rats via Page 56 of 118 gavage  showed clinical signs at 400 mg/ kg/ d and 600 mg/ kg/ d ( with death observed at the higher dose).

4.3.2 Evidence that supports not requiring a Developmental Neurotoxicity study No evidence of increased fetal or offspring susceptibility to acetochlor was observed in four developmental toxicity studies ( two rat and two rabbit), nor in three two generation reproductive toxicity studies in the rat. No evidence of neuropathology or overt neurobehavioral effects to offspring was observed in these studies. Although a transient decrease in hindlimb grip strength was observed in males at week 2, there was no evidence of persistent neurobehavioral effects in the subchronic neurotoxicity study up to the highest tested dose ( 139/ 166.5 mg/ kg/ d via the diet).

<IP_ADDRESS> Rationale for the UFDB ( when a DNT is recommended)

It is possible that the results of the DNT study could impact the current selected regulatory dose for acute oral exposure, since the NOAEL used for that risk assessment endpoint ( 150 mg/ kg/ day) is greater than the NOAELs in the reproductive toxicity study ( 21 mg/ kg/ day) on acetochlor. A DNT study will likely be conducted at dose levels similar to those of the two generation reproductive toxicity study. A 10X database uncertainty factor ( UF DB ) is proposed for acetochlor to account for the lack of a DNT.

4.4 Hazard Identification and Toxicity Endpoint Selection Table 4.4 summarizes the endpoints chosen for use in this risk assessment.

4.4.1 Acute Reference Dose ( aRfD)  General Population Including Females Age 13 49 Study Selected: Acute oral neurotoxicity screening in the rat MRID No. 45357501 Executive Summary: See Neurotoxicity Section of this document ( 4.2.2)

Dose and Endpoint for Establishing aRfD: 150 mg/ kg, based on decreased motor activity in females at 500 mg/ kg on the day of dosing.

Uncertainty Factor ( UF): 1000x ( 10x for interspecies variation, 10x for intraspecies variation and 10x UF DB for lack of developmental neurotoxicity study)

Comments about Study/ Endpoint/ Uncertainty Factor: The effect observed at the selected endpoint ( decreased motor activity in females on the day of dosing) occurred following a single dose. This endpoint is considered protective of females age 13 49 because there are no lower relevant endpoints that may potentially result from a single exposure. Page 57 of 118 Acute RfD for General Population = 150 mg/ kg ( NOAEL) = 0.15 mg/ kg 1000 ( UF)

4.4.2 Chronic Reference Dose ( cRfD)

Study Selected: Chronic ( 1 year) oral toxicity in the dog MRID No. 41565118 Executive Summary: In a chronic toxicity study ( MRID 41565118), SC 5676 ( acetochlor tech., 90.5% a. i., batch/ lot # 1 and 3) was administered to 5 beagle dogs/ sex/ dose in gelatin capsules at dose levels of 0 ( empty capsules only), 2, 10 or 50 mg/ kg bw/ day) for 52 weeks. In addition to the standard parameters evaluated in a chronic oral toxicity study in the dog, plasma and erythrocyte cholinesterase activities ( at 12, 24 and 50 weeks) and brain cholinesterase activity ( termination) were evaluated. A neurological evaluation ( tests examining cranial nerve function, segmental reflexes, postural reactions and general observations) was also performed at Week 47 to assess treatmentrelated signs of toxicity.

At 10 mg/ kg/ day, male dogs showed an increased incidence of salivation following dosing throughout the study ( primarily animal # 1374). Males also showed increased incidence of renal interstitial nephritis ( incidence in control to high dose 0/ 5, 0/ 5, 2/ 5 and 5/ 5, respectively) and renal chronic vasculitis ( control to high dose 0/ 5, 0/ 5, 3/ 5, 4/ 5), tubular degeneration of the testes ( control to high dose 0/ 5, 0/ 5, 4/ 5 and 5/ 5, respectively), hypospermia of the epididymides ( control to high dose 0/ 5, 1/ 5, 2/ 5 and 5/ 5, respectively) and reduced glycogen in the liver ( control to high dose 0/ 5, 1/ 5, 2/ 5 and 4/ 5, respectively). At 50 mg/ kg/ day, the incidence of salivation was markedly increased in females ( beginning in week 13) as well as males and neurologic symptoms including head shaking/ nodding and ataxia ( also hunched posture, abnormal gait, tremor) were reported in both sexes towards the later weeks of the study: severity of neurological symptoms resulted in unscheduled sacrifice of females 1325 in Week 39, 1347 in Week 46, 1329 in Week 48 and 1311 in Week 51 and males 1366 and 1368 in Week 46. Mean body weight gain was reduced ( significantly during weeks 13 26, where weight losses of  0.1 kg in males and  1.2 kg in females were observed; early sacrifice of many animals during the last weeks of the study left only a few animals for body weight evaluation at termination). Water consumption was increased. Changes in clinical chemistry values included increased ALT, GGT ( males) OCT ( males), cholesterol ( males) and triglycerides, along with increased urea, creatinine and decreased glucose. In females, statistically significant increases in plasma AChE at week 24 (+ 26%) and BChE at week 24 (+ 24%) and 50 (+ 33%) were observed. At weeks 23 and 49, significantly increased urinary volume in males and reduced specific gravity in both sexes were observed. Organ weight changes included increased relative brain weight in females, decreased testicular weights in males ( abs and rel) and possibly increased absolute adrenal weights in females, increased relative liver weights in both sexes and thyroid weights in males. Kidneys showed grossly visible abnormal shape and multiple pale areas in males and females. In the kidney of most or all animals of both sexes, cortical fibrosis and/ or scarred areas, collecting duct hyperplasia, dilatation of Bowman's space, cortical atrophy, transitional cell hyperplasia and Page 58 of 118 lipofuchsin pigment in cortical tubules ( one female also showed papillary necrosis and focal necrosis) were reported in the microscopic evaluation. Brain histopathology ( degeneration of the granular layer, 4/ 5 males and 3/ 5 females; depletion of Purkinje cells, 4/ 5 males and 2/ 5 females; demyelination and degeneration of granule cell axons, 1/ 5 males) was observed, along with maturation arrest within the testes ( 5/ 5 males), pigment in hepatocytes ( 1/ 5 each, male and female). There were no treatment related effects observed on brain cholinesterase activity or on ophthalmologic or hematological parameters. The LOAEL is 10 mg/ kg/ day, based on testicular, hepatic and renal histopathology and increased salivation in males. The NOAEL is 2 mg/ kg/ day.

This chronic study in the dog is classified as Acceptable/ guideline and satisfies the guideline requirement for a chronic oral study [ OPPTS 870.4100, OECD 452] in the dog.

Dose and Endpoint for Establishing a cRfD: 2.0 mg/ kg/ day, based on excessive salivation and histopathology of the testes, kidney and liver at 10 mg/ kg/ day.

Uncertainty Factor ( UF): 100x ( 10x for interspecies variation and 10x for intraspecies variation)

Comments about Study/ Endpoint/ Uncertainty Factor: A 10x UF DB was not used in calculation of the UF for this endpoint because the results of the developmental neurotoxicity study are not expected to affect this risk assessment.

Chronic RfD = 2.0 mg/ kg ( NOAEL) = 0.02 mg/ kg 100 ( UF)

4.4.3 Incidental Oral Exposure ( Short and Intermediate Term)

Acetochlor has not been approved for residential uses; therefore, selection of a toxicity endpoint is not necessary for this exposure scenario at this time.

4.4.4 Dermal Absorption A dermal absorption factor of 20% was estimated from an in vivo rat dermal absorption study ( MRID 41778303), based on absorption observed following a 10 hr dermal exposure to acetochlor ( see HIARC Document, TXR # 00135858).

4.4.5 Dermal Exposure ( Short, Intermediate and Long Term)

<IP_ADDRESS> Dermal Exposure: Short Term ( 1 30 Days)

Study Selected: 21 day dermal toxicity in the rabbit Page 59 of 118 MRID No. 00116637 Executive Summary: In a 21 day dermal toxicity study ( MRID 00116637), acetochlor as MON  097 ( 94.5%; Lot No. NBP 1737874) was applied to the abraded and intact shaved skin of groups of 10 New Zealand white rabbits/ sex/ dose at dose levels of 0,100, 400 or 1200 mg/ kg bw/ day, 6 hours/ day for 5 days/ week during a 21 day period.

At 1200 mg/ kg/ day, excessive mortality ( 8/ 10 males and 7/ 10 females) was observed ( first death occurred on Day 7, last on Day 19). Clinical signs of toxicity were first observed on Day 5 and included nasal and ocular discharge, nasal congestion; this group also exhibited possible treatmentrelated signs of anorexia, respiratory congestion, labored breathing, ataxia, hypoactivity, rigid body, tonic convulsions, decreased limb tone, impaired righting reflex, emaciation and hypothermia. No deaths were seen at lower levels and there were no adverse effects on body weight, hematology, clinical chemistry or organ weight but it is noted that there were insufficient surviving high dose animals to evaluate effects at termination. Histopathology revealed skin lesions at the application sites in all treatment groups. Irritation consisted of erythema and edema; desquamation was observed both macroscopically and microscopically in all dosed groups. At day 21, the intensity of dermal irritation was higher in the mid dose group than in the low dose group. The LOAEL ( for systemic effects) is 1200 mg/ kg/ day, based on mortality and clinical signs of toxicity. The NOAEL is 400 mg/ kg/ day. The LOAEL ( for local dermal effects) is 100 mg/ kg/ day, based on skin lesions. The NOAEL is not established.

This 21 day dermal toxicity study in the rabbits is acceptable/ guideline; it satisfies the guideline requirement for a 21 day dermal toxicity study ( OPPTS 870.3200; OECD 410) in the rabbit.

Dose and Endpoint for Risk Assessment: 400 mg/ kg/ day, based on mortality and clinical signs at 1200 mg/ kg/ day.

Comments about Study/ Endpoint: The route and duration of exposure is appropriate for this exposure scenario. Although mortality is an endpoint, it was seen at a dose level which is higher than the limit dose.

<IP_ADDRESS> Dermal Exposure: Intermediate Term ( 1 6 Months)

Study Selected: Subchronic oral toxicity in the dog ( two studies considered together)

MRID Nos. 00050928 and 41565116 Executive Summaries: ( 1) In a 119 day oral toxicity study ( MRID 00050928), CP 55097 ( acetochlor tech., 91.3% a. i., lot # XHK 119) was administered to 6 beagle dogs/ sex/ dose in gelatin capsules at dose levels of 0 ( capsule only), 25, 75 or 200 mg/ kg bw/ day. Due to vomiting observed in a pilot study, mid and high dose animals received gradually increasing dosages as follows to acclimate the dogs to the test material: mid dose, 25 mg/ kg/ day for the first week, 50 mg/ kg/ day for Page 60 of 118 the second week, then 75 mg/ kg/ day for the duration of the study and ( 2) high dose, 50 mg/ kg/ day for the first week, 100 mg/ kg/ day for the second week, 150 mg/ kg/ day for the third week and 200 mg/ kg/ day for the duration of the study.

At 25 mg/ kg/ day, increased liver weights in females ( abs. + 22%, NS and rel + 27%, p< 0.05) and SGPT ( about 2 fold above controls) were observed but were not considered sufficient to establish a LOAEL due to lack of corresponding pathology or other liver enzyme effects. Although mean body weights of males were somewhat lower than controls during the study, this was due to lower initial body weights and gains were comparable. At 75 mg/ kg/ day, one male (# 1281) died at week 11, with diarrhea occurring during week and inactivity in the last weeks prior to death. Mean body weights were lower for much of the study and at termination were + 13% and + 15% lower than controls for males and females, respectively; weight gain at termination was reduced by  42% in males and  50% in females. Food consumption tended to be lower at all weeks in males ( usually 4 to 8% below controls), but not significantly. Increased SGPT was observed in males and females at some time points. Relative liver weights were increased (+ 32% in males and + 22%, females, p< 0.05). Atrophy of the liver in one male and infiltration of the kidney in one male were observed. At 200 mg/ kg/ day, 5 males and 6 females died or were sacrificed in extremis, beginning at week 5, with no females surviving by Week 12 and only one male surviving from week 8 through 17; severity of clinical signs ( bloody diarrhea, vomiting) increased, increased relative liver weight ( males + 13% and females + 17%). Food consumption in males and females was significantly reduced at several time points ( later times not analyzed due to mortality/ unscheduled sacrifice). Mean body weights showed statistically significant reductions in surviving males by Week 4 through 7 ( about  30% below controls at week 7), with weight loss observed during that time and surviving females showed statistically significantly reduced mean body weights from weeks 3 through 10 ( 25 to  47% below controls). Some dogs showed proteinuria and hematuria, primarily at Month 2 ( evaluations not performed later due to mortality). Microscopic findings included hypercellularity of the bone marrow in 3 males and 2 females, atrophy of the liver in one male and one female, infiltration of the kidneys in 2 males and 4 females and thymic atrophy in 4 males and 3 females. There were no biologically significant effects on hematology parameters or gross pathology ( although statistically significantly decreased Hgb and Hct were seen in females at 25 mg/ kg/ day, no dose response was observed and these decreases were not considered treatment related). The LOAEL is 75 mg/ kg/ day, based on decreased body weight/ weight gain, mortality and slight effects on the liver and kidney. The NOAEL is 25 mg/ kg/ day.

This 119 day oral toxicity study in the dog is classified as Acceptable/ guideline and satisfies the guideline requirement for a subchronic oral toxicity study ( OPPTS 870.3150; OECD 409) in the dog.

( 2) In a 90 day oral toxicity study ( MRID 41565116), SC 5675 ( acetochlor tech., 91% a. i., batch/ lot # 1 and 3) was administered to 4 beagle dogs/ sex/ dose in gelatin capsules at dose levels of 0, 2.0, 10 or 60 mg/ kg bw/ day. In addition to the standard parameters evaluated in a guideline subchronic oral study, plasma, erythrocyte and brain cholinesterase were evaluated. Page 61 of 118 At 60 mg/ kg/ day, increased incidence of mucous diarrhea was reported for both sexes, beginning during week 1, and 3 high dose females and 1 male tended to have more liquid feces than other animals. Females had an increased incidence of salivation during the last 5 weeks of the study, occasional emesis and in 2 females, vocalization during defecation was reported from weeks 8 through10. A statistically significantly decrease in mean body weight gain was observed in males ( 32% less than controls) and females ( 40%); in females food consumption was reduced at weeks 12 and 13 ( 15 and  24% below controls, respectively). Also observed were mild anemia in females ( Hct  13%, Hb  9%, RBC  14%), increased alanine aminotransferase ( more than 2 fold greater in males and females), slightly reduced blood glucose ( males and females  13% at week 12) and slightly increased relative liver weight ( males + 13% and females + 17%). There were no treatment related effects observed at # 10 mg/ kg/ day. No mortality, abnormalities of the urinalysis or ophthalmologic parameters, nor alterations in the gross or microscopic pathological evaluation were observed at any dose level. Plasma, erythrocyte and brain cholinesterase were not affected by treatment. The LOAEL is 60 mg/ kg/ day, based on clinical signs of toxicity, decreased body weight gain, mild anemia, slightly increased relative liver weight and increased serum alanine aminotransferase. The NOAEL is 10 mg/ kg/ day.

This 90 day oral toxicity study in the dog is classified as Acceptable/ guideline and satisfies the guideline requirement for a 90 day oral toxicity study ( OPPTS 870.3150; OECD 409) in the dog. Although the test material purity was unspecified in this study report, information on the purity was obtained from other studies on SC 5676 from this laboratory in which batch # 1 and 3 were used. A gradual change in the test material coloration of the sample for daily use ( not bulk storage sample) was reported, but the NOAEL/ LOAEL for this study are within a consistent range of other acceptable subchronic and chronic oral dog studies. When considered together with the information from these other available studies on the oral toxicity studies on the dog, this study is considered acceptable for purposes of risk assessment and no additional data or subchronic studies in the dog are required at this time.

Dose and Endpoint for Risk Assessment: 25 mg/ kg/ day, based on clinical signs of toxicity, decreased body weight gain, mild anemia, slightly increased relative liver weight and increased serum alanine aminotransferase at 60 mg/ kg/ day; data from two dog subchronic studies were used..

Comments about Study/ Endpoint: Oral studies were selected because a dermal study of the appropriate duration was not available. The two subchronic dog studies were considered together to provide the highest NOAEL and the lowest LOAEL ( Study 1  NOAEL 25/ LOAEL 75 and Study 2  NOAEL 10/ LOAEL 60). The selection of this endpoint is further supported by the NOAELs and LOAELs for multigeneration reproductive toxicity studies in rats ( summarized in Table 4.1b; also see Section 4.2.4 on reproductive toxicity for executive summaries). Since an oral NOAEL was selected, the 20% dermal absorption factor should be used in risk assessment. Page 62 of 118 <IP_ADDRESS> Dermal Exposure: Long Term (> 6 Months)

Study Selected: Chronic ( 1 year) oral toxicity in the dog MRID No. 41565118 Executive Summary: See Chronic RfD Section, above ( 4.4.3)

Dose and Endpoint for Risk Assessment: 2.0 mg/ kg/ day, based on excessive salivation and histopathology of the testes, kidney and liver at 10 mg/ kg/ day.

Comments about Study/ Endpoint: An oral study was selected because a dermal study of the appropriate duration was not available. Since an oral NOAEL was selected, the 20% dermal absorption factor should be used in risk assessment.

4.4.6 Inhalation Exposure ( Short, Intermediate and Long Term)

<IP_ADDRESS> Inhalation Exposure: Short Term ( 1 30 Days)

Study Selected: Developmental toxicity in the rat ( oral)

MRID Nos. 41592005, 42054903 Executive Summary: See Developmental Toxicity Section of this document ( 4.2.3)

Dose and Endpoint for Risk Assessment: Developmental NOAEL = 150 mg/ kg/ day, based on increased fetal early resorptions and postimplantation loss, reduced mean fetal weight at 600 mg/ kg/ day.

Comments about Study/ Endpoint: An oral study was selected because there was no inhalation study of appropriate duration. The effects observed at the selected endpoint ( early resorptions, postimplantation loss) are presumed to occur after a single dose. For route to route extrapolation, absorption via the inhalation route is assumed to be equivalent to oral absorption.

<IP_ADDRESS> Inhalation Exposure: Intermediate Term ( 1 6 Months)

Study Selected: Subchronic oral toxicity in the dog ( two studies considered together)

MRID Nos. 00050928 and 41565116 Executive Summaries: See Dermal Exposure: Intermediate Term, above ( Section <IP_ADDRESS>)

Dose and Endpoint for Risk Assessment: 25 mg/ kg/ day, based on clinical signs of toxicity, decreased Page 63 of 118 body weight gain, mild anemia, slightly increased relative liver weight and increased serum alanine aminotransferase at 60 mg/ kg/ day; data from two dog subchronic studies were used.

Comments about Study/ Endpoint/ Uncertainty Factor: Oral studies were selected because there was no inhalation study of appropriate duration. The two subchronic dog studies were considered together to provide the highest NOAEL and the lowest LOAEL on which to base the quantitative hazard estimate ( Study 1  NOAEL 25/ LOAEL 75 and Study 2  NOAEL 10/ LOAEL 60). The selection of this endpoint is further supported by the NOAELs and LOAELs for multigeneration reproductive toxicity studies in rats ( summarized in Table 4.1b; also see Section 4.2.4 on reproductive toxicity for executive summaries). For route to route extrapolation, absorption via the inhalation route is assumed to be equivalent to oral absorption.

<IP_ADDRESS> Inhalation Exposure: Long Term (> 6 Months)

Study Selected: Chronic ( 1 year) oral toxicity in the dog MRID No. 41565118 Executive Summary: See Chronic RfD Section, above ( 4.4.3)

Dose and Endpoint for Risk Assessment: 2.0 mg/ kg/ day, based on excessive salivation and histopathology of the testes, kidney and liver at 10.0 mg/ kg/ day.

Comments about Study/ Endpoint: An oral study was selected because there was no inhalation study of appropriate duration. For route to route extrapolation, absorption via the inhalation route is assumed to be equivalent to oral absorption.

4.4.7 Margins of Exposure The target Margins of Exposure ( MOEs) for residential and occupational exposure and risk assessment are as follows: Page 64 of 118 Route of Exposure Duration of Exposure Short Term ( 1 30 Days) Intermediate Term ( 1 6 Months) Long Term (> 6 Months)

Occupational Exposure Dermal 100 100 100 Inhalation 100 100 100 Residential Exposure Incidental Oral NR NR NR Dermal NR NR NR Inhalation NR NR NR NR not required. There are currently no registered residential uses for acetochlor.

All MOEs above are based on the factors of 10x for interspecies variation and 10x for intraspecies variation. The ( hazard based) special FQPA safety factor is 1X.

4.4.8 Recommendation for Aggregate Exposure Risk Assessments Since there are no residential uses and therefore no expectation of exposure to humans through routes and pathways other than the oral, food plus drinking water, there is no further aggregate risk assessment than the dietary food plus water for this tolerance reassessment.

4.4.9 Classification of Carcinogenic Potential <IP_ADDRESS> Combined Chronic Toxicity/ Carcinogenicity Studies in the Rat ( 1) In an oral combined chronic toxicity/ carcinogenicity study ( MRID 41592004), SC 5676 ( acetochlor, 91.0% a. i., batch # s 1 and 3) was administered to 50 Sprague Dawley CD rats/ sex/ dose in the diet at dose levels of 0, 18, 175 or 1750 ppm ( equivalent to average daily intakes of 0, 0.67, 6.37 or 66.9 mg/ kg bw/ day for males and 0, 0.88, 8.53 or 92.1 mg/ kg bw/ day for females) for 104 consecutive weeks. In addition, 10 CD rats/ sex/ for the 18 and 175 ppm groups and 20 CD rats/ sex for the 0 and 1750 ppm groups were administered the test material for 52 weeks and sacrificed for an interim one year evaluation.

At 1750 ppm ( HDT), decreased mean body weight/ weight gain ( at week 104,  12%/ 14% less than controls, males and  27%/ 24%, females; at week 13, significant decreases of  12% in males and  14% in females were also reported), decreased mean food consumption ( overall study  13%, males and  8%, females), decreased food efficiency ( males 9.1, 9.5, 9.5 and 10.4 g food/ g body weight gain; females 21,7, 19.3, 18.4 and 27.5 g food/ g body weight gain), increased incidence of ocular Page 65 of 118 lesions at the ophthalmologic examinations at 76 and 101 weeks ( in females, hyperreflection and in males, foci or plaques in the vitreous or on the posterior capsule of the lens) were reported. Statistically significant increases in GGT in males at 24, 50, 78 and 102 weeks (+ 50% to + 100% above controls) and cholesterol in males at 102 weeks (+ 66%) were observed, with only marginal changes in GGT and cholesterol seen in females at some time points. Statistically significantly increased microscopic lesions at 1750 ppm included nasal epithelial hyperplasia ( 50%, males and 57%, females, compared to 0%, all other groups), renal pelvic epithelial hyperplasia ( from control to high dose, 12%, 14%, 20% and 44% in males and 8%, 14%, 18% and 28% in females) and degeneration of the outer nuclear layer of the retina ( 4%, 2%, 4% and 14%, males and 26%, 14%, 28% and 48%; significant only in high dose females). Stromal fatty infiltration of the pancreas was also increased but not significantly ( males 18%, 22%, 16% and 30%; females 30%, 38%, 40% and 47%). At the 52 week interim sacrifice, nasal epithelial hyperplasia was reported in 55% of males ( 11/ 20) and 76% of females ( 13/ 16) only at 1750 ppm. Increased relative brain ( females, + 21%), liver, heart and kidney weights at 52 weeks were reported but may have been related to decreased body weights and were not associated with gross or microscopic findings. At 104 weeks in females, slightly decreased brain weight of  3% and increased relative brain weight of + 33% were reported. No compound related, biologically significant effects on mortality, clinical signs, food consumption, hematology parameters, urinalysis parameters or gross pathology were noted. The LOAEL for systemic toxicity is 1750 ppm ( 66.9 mg/ kg bw/ day), based on decreased body weight and weight gain, clinical chemistry alterations and microscopic findings in the retina, nasal epithelium, kidney and possibly pancreas. The NOAEL for systemic toxicity is 175 ppm ( 6.37 mg/ kg bw/ day).

Tumor incidence for this study was reevaluated by the HED CARC ( HED TXR # 0052727, 8/ 5/ 04, fourth cancer evaluation of acetochlor) due to submission of tissue reevaluations for several tumor types by a pathology working group peer review ( MRIDs 44496205, 45367404). The CARC determined that tumor incidences in this study were as follows: ( 1) liver: in males, the incidence of hepatocellular adenomas was 0%, 0%, 0% and 4% ( positive trend only). The incidence of carcinomas was 5%, 7%, 5% and 2%. Combined incidence was 5%, 7%, 5% and 6%. In females, the incidence of adenomas was 0%, 2%, 0% and 4% and no carcinomas were observed The CARC concluded that the tumors were unrelated to treatment due to the low incidence in both sexes; ( 2) thyroid follicular cell: in males, adenoma incidence was 4%, 2%, 4% and 10% ( positive trend only). The incidence of carcinoma was 2%, 6%, 0% and 6%. Combined tumor incidence was 6%, 8%, 4% and 16%. In females, adenoma incidence was 1%, 2%, 5% and 10% ( positive trend observed). The incidence of carcinoma was 0%, 0%, 0% and 2% ( positive trend only) and combined tumors incidence was 1%, 1%, 5% and 11% ( pairwise p< 0.01 with positive trend observed). The CARC determined that the increase was treatment related in both sexes and that the tumors were due to perturbation of thyroid pituitary homeostasis that was secondary to increased clearance of thyroid hormones by hepatic UDPGT activity. The tumors were not included in the cancer quantification; ( 3) nasal olfactory epithelia: the incidence of nasal epithelial adenoma at 1750 ppm ( main study groups) was 50% in males and 57% in females, compared to 0% in controls and lower dose groups ( p# 0.01, both sexes with positive trend). Nasal epithelial carcinoma was reported in 3% of males and 2% of females at 1750 ppm but not in controls or lower dose levels ( tumors and epithelial Page 66 of 118 hyperplasia often were found in the same animal). At the 52 week interim sacrifice, 25% of males and 50% of females at 1750 ppm had adenoma of the nasal epithelium. The CARC concluded that the increased nasal tumors were related to treatment and that mechanistic data were adequate to support a mode of action of tumor formation in the rat; ( 4) bone and stomach: benign chondroma of the femur in 1/ 50 males and benign basal cell tumor of the stomach in 1/ 50 males and 1/ 49 females were reported only at 1750 ppm in the original study report. However, in a Peer Review Working Group histopathology reevaluation ( MRID 45367404), the femur and stomach tumors were reclassified as nonneoplastic lesions ( cartilage hyperplasia, femur and well differentiated squamous cell carcinoma, stomach) and not considered treatment related tumors. The CARC concurred with this reclassification. Dosing was considered adequate based on body weight effects, clinical chemistry alterations and nonneoplastic lesions in both sexes.

This chronic toxicity/ carcinogenicity study in the rat is classified Acceptable/ guideline and satisfies the guideline requirement for a combined chronic toxicity/ carcinogenicity study ( OPPTS 870.4300); OECD 453) in the rat.

( 2) In an oral combined chronic toxicity/ carcinogenicity study ( MRID 40077601), MON 097 ( acetochlor tech., 96.1% a. i., lot # Dayton RDNT 08001) was administered to 60 Sprague Dawley rats/ sex/ dose in the diet at dose levels of 0, 40, 200 or 1000 ppm ( equivalent to estimated average daily intakes of 0, 2.0, 10.0 or 50.0 mg/ kg bw/ day; calculated using a standard conversion factor of 0.05 for conversion of ppm to mg/ kg bw/ day in adult rats) for 24 consecutive months. In addition, groups of 10 rats/ sex/ dose were administered the test material for 12 months and sacrificed for a one year interim evaluation.

At 1000 ppm ( HDT), decreased mean body weight/ weight gain primarily during the second year of the study ( in males at 24 months,  8.5%/ 12.1% less than controls, statistically significant decreases observed between days 455 to 678; and in females  3.2%/ 4.8% less than controls, not statistically significant, although decreases up to  7%/ 10% were observed in the last weeks), decreased food efficiency, statistically significant increases in serum GGT in males at 18 and 24 months (> 300% above controls), cholesterol in males at 24 months (+ 67% above controls) and increased total bilirubin in females at 24 months (+ 363% above controls) were observed. Slightly, statistically significantly increased relative liver weight (+ 18.3% above controls; absolute weight increased + 9.9%, NS) and relative testes weight (+ 11.9%; abs weight + 5.7%, NS) were reported at 12 and 24 months in males and non significantly increased kidney weights at 24 months (+ 10.9% abs/ 15.3% rel), but kidney and testes did not show microscopic effects. A statistically significant increase in thyroid c cell hyperplasia was seen in terminal sacrifice males ( 0%, 12.5%, 4.5% and 34.8%), with a smaller, non significant increase in all males on study ( 4.3%, 7.1%, 5.7% and 11.4%). Nasal mucosal findings similar to those seen in other rat studies showed slight, non significant increases in males at 1000 ppm that were possibly threshold increases, but did not show a clear dose relationship to treatment ( e. g., papillary hyperplasia 1.4%, 1.4%, 5.7% and 7.1%; inflammation of the nasal mucosa 18.6%, 25.7%, 14.3% and 27.1%). Some microscopic findings in the livers ( e. g., hepatocellular alterations, control to high dose 24.3%, 20.0%, 18.6% and 35.7%, and hepatocyte necrosis, 5.7%, 5.7%, 7.1% and 10%) showed marginal increases in males at 1000 ppm ( not Page 67 of 118 statistically significant). Plasma cell hyperplasia of the lymph node was possibly increased in high dose males ( 5.7%, 5.7%, 8.6% and 15.7%). No compound related, biologically significant effects on mortality, clinical signs, food consumption, ophthalmological findings, gross pathological findings or parameters of hematology and urinalysis were noted. The LOAEL is 1000 ppm ( 50.0 mg/ kg bw/ day), based on decreased body weight and weight gain ( both sexes, marginal in females), clinical chemistry alterations and possibly a slight increase in microscopic findings in the nasal epithelium and liver. The NOAEL is 200 ppm ( 10.0 mg/ kg bw/ day).

The relationship of tumors to treatment was evaluated by the HED CARC/ MTARC ( fourth cancer evaluation of acetochlor, HED TXR# 0052727, 8/ 5/ 04), which included review of a PWG reevaluation of liver tumors ( MRID 44496205). The CARC determined that the tumor incidences in this study were as follows: ( 1) liver: the incidence of adenomas in males was 0%, 0%, 0% and 4% ( positive trend only). The incidence of carcinomas was 5%, 7%, 5% and 2% and the combined incidence was 5%, 7%, 5% and 6%. In females, the incidence of adenomas was 0%, 2%, 0% and 4%. The CARC concluded that liver tumors did not show a treatment related increase in this study; ( 2) nasal olfactory epithelium: in males the incidence of papillary adenomas was 1.7%, 0%, 0% and 20.3% ( pairwise p< 0.01 at 1000 ppm with positive trend observed). In females the incidence was 0%, 0%, 0% and 28% ( pairwise p< 0.01 at 1000 ppm with positive trend observed). At interim sacrifice groups, 1/ 10 high dose ( 1000 ppm) female had a papillary adenoma of the mucosa of the nasal turbinates ( included in the above incidence). The CARC determined that the tumors were treatment related; ( 3) thyroid follicular cell: the incidence of thyroid follicular cell adenoma in females was 2.6%, 4.5%, 5.6% and 8.7%. The incidence of carcinoma was 2.8%. Combined tumor incidence was 2.6%, 4.5%, 5.6% and 10.9% ( positive trend only). Males did not show an increase. The CARC concluded that the tumors showed a treatment related increase at 1000 ppm and were secondary to liver effects ( perturbation of pituitary thyroid homeostasis by increased hepatic UDPGT). Dosing was considered adequate based on decreased body weight/ weight gain, clinical chemistry alterations and nonneoplastic lesions in males and females.

This chronic toxicity/ carcinogenicity study in the rat is classified as Acceptable/ guideline and satisfies the guideline requirement for a chronic toxicity/ carcinogenicity study ( OPPTS 870.4300; OECD 453) in the rat.

( 3) In an oral combined chronic toxicity/ carcinogenicity study ( MRID 00131099, reevaluation of nasal pathology in MRID 40484801), MON 097 ( acetochlor tech., 94.5% a. i., lot # NBP 1737874) was administered to 60 Sprague Dawley CD rats/ sex/ dose in the diet at dose levels of 0, 500, 1500 or 5000 ppm ( equivalent to average daily intakes of 0, 22, 69 or 250 mg/ kg bw/ day for males and 0, 30, 93 or 343 mg/ kg bw/ day for females) for 115 consecutive weeks ( males) and 103 consecutive weeks ( females; discontinued earlier due to high mortality). Groups of 10 additional CD rats/ sex/ dose were administered the test material for 52 weeks at the same dose levels and sacrificed at one year for an interim evaluation.

At 500 ppm ( LDT), decreased mean body weight/ weight gain in males during the last 3 months of the study ( at week 115,  14%/ 17.5% less than controls) and increased absolute/ relative mean Page 68 of 118 thyroid weights in females (+ 33% above controls, p< 0.05; increasing to + 33% absolute/+ 100% at 5000 ppm) were observed. Mean relative ( but not absolute) brain weight was statistically significantly increased (+ 14.9%) in males. At 1500 ppm, sporadic statistically significantly decreased mean body weight/ weight gain in females between weeks 31 103 ( e. g.,  9.6%/ 14% below controls at week 79) and slightly increased mean relative thyroid weight in males (+ 22% above controls) were observed. Mean absolute brain weights were reduced in both sexes ( males  3.66%; females  4.6%, p< 0.05) but relative weight in males was increased (+ 20%; unchanged in females). At 5000 ppm, toxicity was excessive. Decreased survival in females ( at 24 months 41.7%, 31.7%, 43.3% and 18.3%, control to high dose) was observed, resulting in termination of all females by Week 103. Male survival at 27 months was 31.7%, 33.3%, 45.0% and 25.0%. Sharply decreased mean body weight/ weight gain in both sexes ($ 30% below controls in the second year of the study), occasional statistically significantly decreased food consumption, significantly decreased hematocrit ( up to  15.5% less than controls) and hemoglobin ( up to  18% less than controls) in females at 6, 12 and 18 months were also observed. Thyroid relative weight was significantly increased by + 50% in males; absolute weight was increased 40% but was not significant and relative liver weights were significantly increased in both sexes. Brain absolute weights were reduced ( 5.4% males,  10%, females) but relative weights were increased (+ 50%, males and + 32%, females). Microscopic lesions significantly increased at 5000 ppm ( p# 0.05) included nasal mucosal inflammation in males ( control to high dose, 4.3%, 12.9%, 10.1% and 23.2%), polyarteritis of the testes ( 10%, 15.7%, 17.1% and 24.3%) and gastric fibrosis in females ( 5.7%, 7.1%, 10% and 17.1%). The incidence of nasal inflammatory epithelial hyperplasia in males was 1.4%, 0%, 2.9% and 4.3% ( not significant) and in females was 1.4%, 0%, 2.9% and 0%. Incidence of inflammation of nasal mucosa in females was 2.9%, 11.4%, 8.7% and 11.6% ( not significant). Peripheral nerve neuropathy was reported in 4 females ( not significant). No compound related, biologically significant effects on clinical signs of toxicity, ophthalmologic findings, clinical chemistry or urinalysis parameters were reported. The LOAEL is # 500 ppm ( 22 mg/ kg bw/ day), based on slightly decreased body weight/ weight gain in males and increased abs/ rel thyroid weights in females. A NOAEL was not established (< 500 ppm or 22 mg/ kg/ day).

Tumor incidence for this study was reevaluated by the HED CARC ( HED TXR # 0052727, 8/ 5/ 04, fourth cancer evaluation of acetochlor) due to submission of tissue reevaluations of liver tumors in this study by a pathology working group peer review ( MRIDs 44496205). The CARC determined that tumor incidences in this study were as follows: ( 1) liver: In males, the incidence of hepatocellular adenoma was 3%, 2%, 2% and 11% ( positive trend only). The incidence of carcinomas was 2%, 5%, 5% and 11% ( positive trend only). Combined tumor incidence was 5%, 7%, 7% and 20% ( pairwise p< 0.05 at 5000 ppm with positive trend observed. In females the incidence of adenoma was 0%, 0%, 2% and 7% ( pairwise p< 0.05 at 5000 ppm with positive trend observed). The incidence of carcinomas was 0%, 0%, 0% and 13% ( positive trend only). The incidence of combined tumors was 0%, 0%, 2% and 12% ( pairwise p< 0.01 at 5000 ppm with positive trend observed). The CARC concluded that although these tumors showed a treatmentrelated increase at 5000 ppm they were observed only at a dose that caused excessive toxicity and should not be included in the weight of evidence determination for acetochlor; ( 2) thyroid follicular cell: in males, the incidence of adenoma was 0%, 0%, 4.3% and 7.1% ( p< 0.05 at 5000 ppm). The Page 69 of 118 incidence of adenoma in females was 2.9%, 0%, 0% and 4.3%, with no carcinomas observed. The CARC determined that thyroid tumors in both sexes were treatment related and secondary to perturbation of thyroid pituitary homeostasis by increased UDPGT activity, but that toxicity at 5000 ppm was excessive; ( 3) nasal olfactory epithelia: In a reevaluation of nasal tissues from this study, an increased incidence of nasal papillary adenomas ( posterior nasal cavity) in males at 0%, 1.4%, 8.7% ( p# 0.05) and 26.1% ( p# 0.01) was observed and at 5000 ppm only, there were 2/ 69 papillary adenocarcinomas of the nasal turbinates ( not significant). Females had only 2/ 70 and 1/ 69 papillary adenomas of the nasal turbinates at 1500 and 5000 ppm, respectively ( not significant). The CARC considered the nasal tumors treatment related but toxicity at 5000 ppm was excessive. Mechanistic data was considered sufficient to support a proposed mode of action for nasal tumors. Dosing was considered adequate at 500 and 1500 ppm for males and females based on body weight effects, clinical chemistry alterations and nonneoplastic lesions, but toxicity at 5000 ppm was excessive.

This chronic toxicity/ carcinogenicity study in the rat is classified as Acceptable/ guideline and satisfies the guideline requirement for a chronic toxicity/ carcinogenicity study ( OPPTS 870.4300; OECD 453) in the rat.

<IP_ADDRESS> Carcinogenicity Studies in the Mouse ( 1) In an oral carcinogenicity study ( MRID 41565119), SC 5676 ( acetochlor tech., 90.5% a. i., batch nos. 1 and 3) was administered to 50 CD 1 mice/ sex/ dose in the diet for 78 weeks at dose levels of 0, 10, 100 or 1000 ppm ( equivalent to an average daily intake of 0, 1.1, 11 or 116 mg/ kg bw/ day, males and 0, 1.4, 13 or 135 mg/ kg bw/ day, females). Additional groups of 10 CD 1 mice/ sex/ dose were administered the test material at the above dose levels for 52 weeks for interim sacrifice at one year.

At 10 ppm and above, males showed statistically significant increases in absolute kidney weights ( low to high dose + 8.2%, + 12.9% and + 29.4% above controls) associated with increased incidence of renal tubular basophilia ( from control to high dose, 5%, 33%, 28% and 44% affected, respectively); however, these findings at 10 or 100 ppm were not considered clearly adverse. At 100 ppm in males, the incidence of bronchiolar hyperplasia was significantly ( p< 0.05) increased ( control to high dose 13%, 10%, 39% and 38%) and relative kidney weights were significantly increased at 100 ppm (+ 15.8%) and 1000 ppm (+ 36.6%) and a single male had renal tubular epithelial hyperplasia ( 0% at control and low dose). At 1000 ppm in males, statistically significantly increased incidence of nephropathy ( cortical mineralization, hyaline casts, interstitial fibrosis, tubular epithelial hyperplasia; all increased by more at least two fold relative to controls and lower dose groups) were reported. At 1000 ppm in females, a statistically significant increase in the incidence of anterior polar vacuoles in the ocular lens was observed at 76 weeks, with a slight, non significant doserelated increase observed at lower dose levels ( from control to high dose, percent incidence was 19%, 24%, 32% and 54%, respectively) but were not associated with increased ocular opacities. A statistically significant decrease ( 3.8% below controls) in absolute brain weight was observed ( relative weight  3.4%, not significant), with no associated histopathology. Slight but statistically significant decreases in some RBC parameters were observed in males at 50 and/ or 76 weeks and Page 70 of 118 females at 50 weeks, but were of small magnitude (< 10%). Males in the interim sacrifice 1000 ppm group had nephropathy ( 44% vs. 0%, controls); a slight increase was observed in females ( 20% vs. 10% controls) but this finding was not observed in females at terminal sacrifice. There were no treatment related clinical signs and no biologically significant effects on survival, food consumption, body weight or weight gain. The systemic toxicity LOAEL in males is 100 ppm ( 11 mg/ kg bw/ day), based on an increased incidence of bronchiolar hyperplasia and possibly renal tubule epithelial hyperplasia. The systemic toxicity NOAEL in males is 10 ppm ( 1.1 mg/ kg/ day). The systemic toxicity LOAEL in females was not achieved (> 1000 ppm or 135 mg/ kg bw/ day).

Tumor incidence for this study was reevaluated by the HED CARC ( HED TXR # 0052727, 8/ 5/ 04) due to submission of tissue reevaluations for several tumor types by a pathology working group peer review ( MRIDs 44496204,  05,  06). The CARC determined that tumor incidences in this study were as follows: ( 1) lung tumors: the incidence of pulmonary adenomas ( alveologenic) was 15%, 8%, 19% and 30% ( pairwise at high dose p< 0.05; positive trend also observed) in males and 7%, 8%, 10% and 15% in females. The incidence of carcinomas was 5%, 5%, 5% and 7% in males and 2%, 0%, 3% and 3% in females. The combined tumor incidence was 18%, 13%, 22% and 33% ( pairwise at high dose p< 0.05 with positive trend also observed) in males and 9%, 8%, 14% and 18% ( positive trend only) in females. In the interim sacrifice groups, one high dose female and one mid dose male had pulmonary adenomas. Based on these findings and available historical control data, the CARC determined that the increased incidence of adenoma in males and combined lung tumors in both sexes was treatment related. ( 2) liver tumors: the incidence of liver carcinomas in males showed a positive trend ( 0%, 5%, 7%, 8%). The incidences of liver adenoma ( 14%, 21%, 12% and 16%) and combined tumors ( 14%, 26%, 20% and 24%) showed no significant change. Females did not show an increase in these tumors. Based on these findings and available historical control data, the CARC concluded that the liver tumor incidence was within historical range and did not show a treatment related effect. ( 3) uterus histiocytic sarcoma: the incidence of histiocytic sarcoma in females was 3%, 2%, 0% and 8% ( positive trend only). The CARC concluded that when considered with the 23 month mouse study, a positive dose response was observed and that the increase at 1000 ppm was treatment related. Although kidney effects in males and ocular effects in females were reported in this study, neither males nor females showed effects considered sufficient to demonstrate achievement of an MTD. However, dosing was considered adequate in males based on the finding of significantly decreased body weight gain ( 9% less than controls) at 1200 ppm in a sixweek range finding study. In females, body weight effects were not achieved in the range finding study but additional testing was not considered necessary based on the significantly increased incidence of pulmonary adenoma observed in both males and females at 1000 ppm. In addition, the MTD was achieved for both males and females in a separate mouse carcinogenicity study ( MRID 00131089; see review in HED TXR# 004586 and Supplemental DER, TXR # 0050658). Additional mouse oncogenicity testing is therefore not required at this time.

This carcinogenicity study in the mouse is classified as Acceptable/ Guideline and satisfies the guideline requirement for a carcinogenicity study in the mouse [ OPPTS 870.4200; OECD 451]. Page 71 of 118 ( 2) In an oral carcinogenicity study ( MRID 00131089), MON 097 ( acetochlor tech., 94.5% a. i., lot # NBP 1737874) was administered to 50 Swiss bred CD 1 albino mice/ sex/ dose in the diet for 23 months at dose levels of 0, 500, 1500 or 5000 ppm ( equivalent to an estimated average daily intake of 0, 75, 225 or 750 mg/ kg bw/ day; calculated using a dietary ppm to mg/ kg/ day conversion factor of 0.15 for mice). Additional groups of 10 mice/ sex/ dose were administered the same diets for 12 months and sacrificed for a one year interim evaluation.

At 500 ppm and above, statistically significantly increased absolute/ relative kidney weights were observed in males at the interim and terminal sacrifices ( at 23 months, abs/ rel wt was increased + 39.5%/+ 39.1%, + 42.1%/+ 45.3% and + 14.5%/+ 38.9% above controls, low to high dose). Statistically significantly increased mean abs/ rel liver weights were observed at all dose levels in males at interim and terminal sacrifice ( at 23 months, + 29.5%/+ 28.5, + 23.5%/+ 23.7 and + 55.6%/+ 91.4% above controls, low to high dose, respectively), with females showing significant increases only at the interim sacrifice time ( abs/ rel wt + 11.5%/+ 13.9%, + 24.6%/+ 23.5% and + 17.8%/+ 45.3%). ( In the absence of correlated microscopic/ clinical chemistry findings, liver and kidney organ weight changes at low and mid dose were not used to establish a LOAEL; increased liver weights at terminal sacrifice in the high dose group may have reflected, in part, the presence of tumors). At 1500 ppm in males, slight effects on mean body weights ( 4.7% and  6.5% below controls at 53 and 79 weeks, p< 0.05 but not significant at termination) and slightly increased incidence of interstitial nephritis ( from control to high dose, 50%, 58.3%, 70% and 83.3%) were observed. In females, survival was reduced during the last months of the study ( 62%, 50%, 34% and 26% at termination) and abs/ rel thyroid plus parathyroid weights were increased (+ 29%/+ 39% and at 5000 ppm + 43%/ 68%). At 5000 ppm ( HDT), survival was also significantly reduced in males, beginning at about 1 year ( at termination, control to high dose 60%, 50%, 50% and 26%, respectively), mean body weights were significantly reduced in both males and females throughout the study ( up to about 20% by study termination), and females showed significant decreases in RBC count ( 21% below controls), Hgb ( 22.5%) and Hct ( 23%); relative thyroid weight in males was increased by + 31%; and at 23 months, the incidence of interstitial nephritis was also statistically significantly increased in females ( control to high dose 51.6%, 55%, 51.6% and 76.3%, females). A significantly increased incidence of retinal degeneration was seen in females ( control to high dose 2/ 60, 3/ 60, 1/ 60 and 8/ 59). There were no treatment related effects observed on clinical signs of toxicity, food consumption/ feed efficiency, nor in clinical chemistry or urinalysis parameters. The systemic toxicity LOAEL is 1500 ppm ( 225 mg/ kg/ day), based on slightly reduced mean decreased body weight and increased incidence of interstitial nephritis in males and increased mortality and abs/ rel thyroid plus parathyroid weights in females. The systemic toxicity NOAEL is 500 ppm ( 75 mg/ kg/ day).

Tumor incidence for this study was reevaluated by the HED CARC ( HED TXR # 0052727, 8/ 5/ 04) due to submission of tissue reevaluations for several tumor types by a pathology working group peer review ( MRIDs 44496204,  05,  06 and 45367403). The CARC determined that tumor incidences in this study were as follows: ( 1) liver  in males, the incidence of hepatocellular adenomas was 16%, 18%, 22% and 48% ( pairwise p< 0.01 at 5000 ppm with positive trend also observed). The incidence of carcinoma was 9%, 11%, 9% and 23% ( p< 0.05 at 5000 ppm, positive trend observed) Page 72 of 118 and combined tumors was 24%, 26%, 31% and 65% ( pairwise p< 0.01 at 5000 ppm with positive trend observed). In females, the incidence of adenomas was 5%, 0%, 3% and 21% ( pairwise p< 0.05 at 5000 ppm with positive trend), of carcinomas was 0%, 0%, 0% and 9% ( trend only) and combined tumors was 5%, 0%< 3% and 29% ( pairwise p< 0.01 at 5000 ppm with positive trend observed). The CARC concluded that an increase in liver tumors was only observed at the excessive dose of 5000 ppm and should not be included in the cancer weight of evidence determination for acetochlor; ( 2) lung  in females, the incidence of adenoma was 2%, 17%, 22% and 23% ( pairwise p< 0.05 at 500 ppm and p< 0.01 at 1400 and 5000 ppm with positive trend also observed). The incidence of carcinomas was 0%, 9%, 2% and 18% ( pairwise p< 0.05 at 500 ppm and p< 0.01 at 5000 ppm with positive trend also observed). Combined lung tumor incidence was 2%, 23%, 25% and 33% ( pairwise p< 0.01, all doses with positive trend also observed). Males did not show an increase. The CARC concluded that the lung tumors in females were treatment related at 500 and 1500 ppm ( 5000 ppm was excessive dose), based on incidence exceeding available historical control data; ( 3) uterus  histiocytic sarcoma  the incidence in females was 0%, 7%, 15% and 15% ( pairwise p< 0.05 at low and high dose and p< 0.01 at mid dose). The CARC concluded that the tumors were related to treatment and should be included in the cancer classification of acetochlor, based on significant increases at 500 and 1500 ppm ( 5000 ppm excessive dose); ( 4) kidney  the incidence of renal adenoma was 0%, 0%, 0% and 14% ( positive trend only) in males and 0%, 0%, 0% and 7% in females. The CARC concluded that these tumors were not related to treatment based on low incidence and occurrence only at an excessively toxic dose of 5000 ppm; ( 5) ovaries  benign tumors ( adenoma, granulosa cell tumor and luteoma) were determined not to be related to treatment based on low incidence of each type. It was determined that it was not appropriate to combine the incidence of these types of tumors. Dosing was considered adequate, based on slightly reduced survival in females and slightly reduced body weights and increased interstitial nephritis in males at 1500 ppm; toxicity at 5000 ppm was considered excessive in both sexes based on pronounced effects ( sharply reduced survival, anemia, reduced body weight in both sexes and renal toxicity).

This carcinogenicity study in the mice is classified as Acceptable/ guideline and satisfies the guideline requirement for a carcinogenicity study [ OPPTS 870.4200; OECD 451] in mice.

<IP_ADDRESS> Cancer Classification The carcinogenicity of acetochlor was evaluated by the HED CARC/ MTARC in a joint meeting ( April 21 22, 2004). Three carcinogenicity studies in the rat and two in the mouse were submitted for acetochlor. In addition, numerous mechanistic studies were submitted to evaluate the mechnism of nasal, thyroid and liver tumorigenesis. Acetochlor is classified as " Likely to be Carcinogenic to Humans" based on treatment related increases in lung tumors in male and female mice, histiocytic sarcoma in female mice and nasal epithelial and thyroid follicular cell tumors in male and female rats. Mechanistic data supports non mutagenic ( threshold) mechanisms of carcinogenicity for the rat nasal and thyroid tumors ( see Section <IP_ADDRESS>). Genotoxicity data do not indicate that acetochlor has high genotoxic potential in vivo. Weak positive findings in some studies ( UDS, dominant lethal) appeared to be related to cytotoxicity secondary to depleted cellular glutathione reserves. Although the available genotoxicity data do not provide strong support for a mutagenic mechanism of Page 73 of 118 carcinogenicity, the Committee recommended that in the absence of supporting mechanistic data for the formation of lung tumors and histiocytic sarcomas in mice, a default linear low dose extrapolation should be used to estimate cancer risk for those tumors. Calculation of a Q1 * of 3.27 x 10 2 ( mg/ kg/ day)  1 was based on lung tumor incidence in male mice. Nasal and thyroid tumors in rats were not included as part of the quantitation of tumor risk.

Table 4.4. Summary of Toxicological Doses and Endpoints for Acetochlor for Use in Human Risk Assessments Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary ( general population including females age 13 49) NOAEL = 150 mg/ kg/ day UF = 1000 Acute RfD = 0.15 mg/ kg/ day FQPA SF = 1X aPAD = acute RfD ( 0.15) FQPA SF ( 1)

= 0.15 mg/ kg/ day Acute oral neurotoxicity in rats LOAEL = 500 mg/ kg/ day, based on decreased motor activity in females.

Chronic Dietary ( all populations) NOAEL = 2.0 mg/ kg/ day UF = 100 Chronic RfD = 0.02 mg/ kg/ day FQPA SF = 1X aPAD = chronic RfD ( 0.02) FQPA SF ( 1)

= 0.02 mg/ kg/ day Chronic oral toxicity in beagle dogs LOAEL = 10 mg/ kg/ day, based on increased salivation and histopathology in the testes, kidney and liver.

Incidental Oral Short Term ( 1  30 days) Not determined ( there are no registered residential uses for acetochlor)

Incidental Oral Intermediate Term ( 1  6 months) Not determined ( there are no registered residential uses for acetochlor)

Dermal Short Term ( 1  30 days) NOAEL = 400 mg/ kg/ day Residential LOC for MOE = Not applicable Occupational LOC for MOE = 100 21 day dermal toxicity study in rabbits LOAEL = 1200 mg/ kg/ day, based on mortality and clinical signs of toxicity.

Dermal Intermediate Term ( 1  6 months) NOAEL = 25 mg/ kg/ day ( dermal absorption rate 20%)

NOAELadj = 125 mg/ kg/ day Residential LOC for MOE = Not applicable Occupational LOC for MOE = 100 Subchronic oral toxicity in beagle dogs ( two studies considered together) LOAEL = 60 mg/ kg/ day, based on decreased body weight/ weight gain, slight anemia, slight liver effects. Table 4.4. Summary of Toxicological Doses and Endpoints for Acetochlor for Use in Human Risk Assessments Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and Level of Concern for Risk Assessment Study and Toxicological Effects Page 74 of 118 Dermal Long Term (> 6 months) NOAEL = 2.0 mg/ kg/ day ( dermal absorption rate 20%)

NOAELadj = 10 mg/ kg/ day Residential LOC for MOE = Not applicable Occupational LOC for MOE = 100 Chronic oral toxicity in beagle dogs LOAEL = 10 mg/ kg/ day, based on increased salivation and histopathology in the testes, kidney and liver.

Inhalation Short Term ( 1  30 days) NOAEL = 150 mg/ kg/ day ( Assume inhalation absorption = oral absorption) Residential LOC for MOE = Not applicable Occupational LOC for MOE = 100 Developmental toxicity study in rats ( oral) Developmental LOAEL = 600 mg/ kg/ day, based on decreased fetal weight; increased resorptions and postimplantation loss.

Inhalation Intermediate Term ( 1  6 months) NOAEL = 25 mg/ kg/ day ( Assume inhalation absorption = oral absorption) Residential LOC for MOE = Not applicable Occupational LOC for MOE = 100 Subchronic oral toxicity in beagle dogs ( two studies considered together) LOAEL = 60 mg/ kg/ day, based on decreased body weight/ weight gain, slight anemia, slight liver effects.

Inhalation Long Term (> 6 months) NOAEL = 2.0 mg/ kg/ day ( Assume inhalation absorption = oral absorption) Residential LOC for MOE = Not applicable Occupational LOC for MOE = 100 Chronic oral toxicity in beagle dogs LOAEL = 10 mg/ kg/ day, based on increased salivation and histopathology in the testes, kidney and liver.

Cancer ( oral, dermal, inhalation) Classification: Likely to be carcinogenic to humans, based on increased incidence of lung tumors in male and female mice, histiocytic sarcoma in female mice and nasal epithelial tumors and thyroid follicular cell adenomas in male and female rats. Q1 * = 3.27 x 10 2, based on lung tumor incidence in male mice.

UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose ( a = acute, c = chronic) RfD = reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable * Refer to Section 4.5 Page 75 of 118 4.5 Special FQPA Safety Factor Based upon the hazard data presented above, it is recommended that the special FQPA SF be reduced to 1x because there are no/ low concerns and no residual uncertainties with regard to pre and/ or postnatal toxicity.

4.6 Endocrine disruption EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to determine whether certain substances ( including all pesticide active and other ingredients) " may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." Following recommendations of its Endocrine Disruptor and Testing Advisory Committee ( EDSTAC), EPA determined that there was a scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program ( EDSP).

Studies in the rat evaluating thyroid and liver effects following dietary administration of acetochlor at various dose levels indicate that acetochlor may disrupt thyroid pituitary homeostasis via increased hepatic UDPGH mediated increased clearance of the thyroid hormone thyroxine ( T4). Slightly increased incidence of thyroid follicular cell tumors have been observed in rat two year bioassay studies at higher dose levels. Structure activity relationship data on the related chloroacetanilide herbicides alachlor and butachlor support this conclusion. The available data do not indicate that acetochlor disrupts androgen or estrogen hormone systems.

When additional appropriate screening and/ or testing protocols being considered under the Agency's EDSP have been developed, acetochlor may be subjected to further screening and/ or testing to better characterize effects related to endocrine disruption. Page 76 of 118 5.0 Public Health Data 5.1 Incident Reports In addition to the Scientific Literature, the following data bases have been consulted for the poisoning incident data on the active ingredient Acetochlor (" Review of Acetochlor Incident Reports", Memorandum from J. Blondell, HED) to A. Protzel ( HED) dated July 5, 2005, DP Barcode D318498):

1) OPP Incident Data System ( IDS) 2) Poison Control Centers 3) California Department of Pesticide Regulation 4) National Pesticide Information Center ( NPIC) 5) National Institute of Occupational Safety and Health's Sentinel Event Notification System for Occupational Risks ( NIOSH SENSOR)

The few reports of acetochlor exposure mostly involve minor effects to the eyes and skin. No recommendations are made based on the limited information available.

5.2 Other 1. Ag Health Data Acetochlor was not among the chemicals named in the Agricultural Health Study ( AHS) Phase 1 questionnaire. There is not a final AHS publication specifically on acetachlor.

In a chemical closely related to acetochlor, the Alachlor chemical specific AHS publication ( Lee WJ et al. 2004 Am J Epid; 159), found " a significant increasing trend for incidence or all lymphohematopoietic cancer associated with lifetime exposure days ( p for trend = 0.02) and intensity weighted exposure days ( p for trend = 0.03). The authors caution that the number of cases is small. " Additional follow up of this cohort will shed further light on the risks for these and other cancers as the number of cancer cases increases over time."

2. NHANES Data. Acetochlor was not among the chemicals examined in NHANES III ( 1988 94) human biomonitoring assessment. The metabolite acetochlor mercapturate was among the chemicals measured in the NHANE99+ ( 1999 2000 and 2001 2002).

6.0 Exposure Characterization/ Assessment 6.1 Dietary Exposure/ Risk Pathway 6.1.1 Residue Profile Acetochlor, 2 chloro N( ethoxymethyl) N( 2 ethyl 6 methylphenyl) acetamide, is a chloroacetanilide herbicide used for preemergence control of weeds in corn. In the United States, acetochlor is Page 77 of 118 conditionally registered for use on field corn to the Acetochlor Registration Partnership ( ARP), which is comprised of Dow AgroSciences, LLC ( Dow) and Monsanto Company ( Monsanto). In addition to the ARP members, Drexel Chemical Company ( Drexel), Syngenta Crop Protection, Inc. ( Syngenta) and Tenkoz, Inc. ( Tenkoz) also have end use products containing acetochlor. Acetochlor is formulated as a variety of emulsifiable concentrate ( EC), soluble concentrate ( SC), microencapsulated ( Mcap), or granular ( G) formulations that can be applied to field corn as a preplant, preemergence, or early postemergence application using only ground equipment.

For the use on field corn, the nature of the residues in plants is adequately understood based on adequate corn metabolism studies and the confined rotational crop study. The HED Metabolism Committee ( M. Flood, 9/ 30/ 1993) determined that the residues of concern in corn include parent and the its ethyl methyl aniline ( EMA) and hydroxyethyl methyl aniline ( HEMA) producing metabolites. For purposes of the dietary risk assessment, residues in rotational crops also include metabolites containing the hydroxymethyl ethyl aniline ( HMEA) moiety, expressed in acetochlor equivalents.

The qualitative nature of acetochlor residues in livestock is also adequately understood, although the studies using direct dosing with 14C acetochlor are not fully acceptable. Adequate studies are available examining the metabolism of various classes of plant metabolites ( EMA, HEMA, and Metabolite 57) in both ruminants and poultry. Based on these studies, the Agency concluded that acetochlor residues in ruminants and poultry include EMA and HEMA type metabolites and Metabolite 57.

Tolerances are established for the combined residues of acetochlor and its metabolites convertible to EMA or HEMA, to be analyzed as acetochlor, and expressed as acetochlor equivalents [ 40 CFR § 180.470]. Tolerances range from 0.05 to 1.5 ppm in/ on field corn ( forage, grain, and stover) resulting from the direct use of acetochlor and from 0.02 to 1.0 ppm in commodities from rotational crops of sorghum, soybean, or wheat. There are no tolerances for residues in livestock commodities.

Adequate methods are available for enforcing tolerances and collecting data on acetochlor residues in/ on plant and livestock commodities. The high performance liquid chromatography with oxidative coulometric electrochemical detection enforcement methods are listed as Method I for plants commodities and Method A for livestock commodities in PAM Vol. II. The validated limit of quantitation ( LOQ) for the method is 0.02 ppm for each analyte.

Considering the data from the available livestock metabolism and feeding studies and the calculated maximum theoretical dietary burdens ( MTDBs) of 3.0 3.8 ppm for cattle and 0.04 ppm for poultry and swine, the Agency concluded that there is no reasonable expectation of quantifiable residues of acetochlor or its metabolites occurring in livestock commodities. Therefore, tolerances for livestock commodities are not required at the present time.

Adequate field trial data are available to support the use of acetochlor on field corn as a preplant, preemergence, or early post emergence application. An adequate number of tests were conducted in Page 78 of 118 the appropriate geographical regions using representative formulations applied at the maximum labeled use rate of 3.0 lb ai/ A. These studies are also supported by adequate storage stability data. The maximum combined residues of acetochlor and its EMA and HEMA type metabolites, expressed in acetochlor equivalents, resulting from use of acetochlor at the maximum application rate were < 0.05 ppm in grain, 2.52 ppm in forage, and 1.08 ppm in fodder. The available corn grain processing studies indicate that acetochlor, its EMA and HEMA type metabolites, and Metabolite 57 do not concentrate in processed corn grain fractions.

Adequate confined rotational crop studies and adequate field rotational crops studies are available supporting the label specified restrictions allowing rotation to only corn, soybeans, sorghum, wheat and tobacco. The available residue data support the current tolerances on rotational sorghum, soybean, and wheat commodities and indicate that residues do not concentrate in processed fractions derived from these rotational crops.

6.1.2 Acute and Chronic Dietary Exposure and Risk Acute, chronic, and cancer dietary ( food and water) exposure assessments were conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database ( DEEMFCID   , Version 2.03), which uses food consumption data from the USDA's Continuing Surveys of Food Intakes by Individuals ( CSFII) from 1994 1996 and 1998. The acute, chronic, and cancer dietary risk assessments were conducted for all supported acetochlor food uses and were performed to support the tolerance reassessment eligibility decision. See: Acetochlor. Acute, Chronic, and Cancer Dietary Exposure Assessments for the Tolerance Reassessment Eligibility Decision ( TRED). PC Code: 121601, DP Barcode: D297061. Samuel Ary . June 30, 2005 Acute Dietary Exposure Results and Characterization of Input Data The acute dietary exposure assessment incorporated tolerance level residues for all crops and percent crop treated data provided by the Acetochlor Registration Partnership ( ARP) in MRID 45322101. Processing data were available for all commodities and incorporated into the assessment. The assessment also included the highest water concentration generated from the ARP acetochlor water monitoring program. Acute dietary risk estimates are provided for the general U. S. population and various population subgroups, with the major emphasis placed on the exposure estimates for infants and children. This assessment concludes that for all supported registered commodities, the acute dietary risk estimates do not exceed HED's level of concern ( less than 100% of the aPAD) at the 99.9th exposure percentile for the U. S. population at 2% of the aPAD and all population subgroups, with the highest exposed population subgroup being infants less than 1 year old at 6% of the aPAD.

Chronic Dietary Exposure Results and Characterization of Input Data Page 79 of 118 The chronic dietary exposure assessment incorporated tolerance level residues for all crops and percent crop treated data provided by the ARP in MRID 45322101. Processing data were available for all commodities and incorporated into the assessment. The assessment also included the highest time weighted annualized mean ( TWAM) water concentration generated from the ARP acetochlor water monitoring program. Chronic dietary risk estimates are provided for the general U. S. population and various population subgroups, with the major emphasis placed on the exposure estimates for infants and children. This assessment concludes that for all supported registered commodities, the chronic dietary risk estimates do not exceed HED's level of concern ( less than 100% of the cPAD) for the U. S. population and all population subgroups ( all were less than 1% of the cPAD).

Cancer Dietary Exposure Results and Characterization of Input Data The cancer dietary exposure assessment incorporated tolerance level residues for all crops and percent crop treated data provided by the ARP in MRID 45322101. Processing data were available for all commodities and incorporated into the assessment. The assessment also included the highest overall multi year time weighted annualized mean water concentration generated from the ARP acetochlor water monitoring program. The estimated exposure of the general U. S. population to acetochlor is 0.000026 mg/ kg/ day. Applying the Q 1 * of 3.27 x 10 2 ( mg/ kg/ day) 1 to the exposure value results in a cancer risk estimate of 8.40 x 10 7. Therefore, the cancer dietary risk estimate does not exceed HED's level of concern of 1.0 x 10 6.

Table 6. 1 Summary of Dietary ( food + water) Exposure and Risk for Acetochlor Population Subgroup Acute Dietary ( 99.9th Percentile) Chronic Dietary Cancer Dietary Exposure ( mg/ kg/ day) % aPAD Dietary Exposure ( mg/ kg/ day) % cPAD Dietary Exposure ( mg/ kg/ day) Risk General U. S. Population 0.003613 2 0.000050 < 1 0.000026 8.40 x 10 7 All Infants (< 1 year old) 0.009168 6 0.000129 < 1 N/ A N/ A Children 1 2 years old 0.003635 2 0.000086 < 1 Children 3 5 years old 0.003611 2 0.000087 < 1 Children 6 12 years old 0.002187 1 0.000063 < 1 Youth 13 19 years old 0.002350 2 0.000048 < 1 Adults 20 49 years old 0.002682 2 0.000044 < 1 Adults 50+ years old 0.001861 1 0.000039 < 1 Table 6. 1 Summary of Dietary ( food + water) Exposure and Risk for Acetochlor Population Subgroup Acute Dietary ( 99.9th Percentile) Chronic Dietary Cancer Dietary Exposure ( mg/ kg/ day) % aPAD Dietary Exposure ( mg/ kg/ day) % cPAD Dietary Exposure ( mg/ kg/ day) Risk Page 80 of 118 Females 13 49 years old 0.002543 2 0.000044 < 1 The bolded values represent the highest exposed populations for each of the risk assessments.

6.2 Water Exposure/ Risk Pathway The drinking water values used in the dietary risk assessment were generated by the ARP acetochlor water monitoring program. The Environmental Fate and Effects Division ( EFED) analyzed and reported the data in the following memorandum: " Drinking Water Exposure Assessment for Acetochlor" ( M. Barrett, EFED Memorandum, 1/ 3/ 2005). Water residues were incorporated in the DEEM FCID   into the food categories " water, direct, all sources" and " water, indirect, all sources". Characterization of the water monitoring program and complete details of the uncertainties associated with the program may be found in the EFED memorandum. A highlight of the uncertainties associated with the water monitoring program are listed below.

° The surface drinking water supply ( SDWS) and state ground water ( SGW) monitoring programs were designed to focus on areas of high acetochlor use. The monitoring does not cover the entire geographic distribution of acetochlor use. A lower rate of utilization of surface water sources by drinking water facilities and lower overall numbers of CWS' utilizing surface water in these high acetochlor use regions appears to be a factor in the paucity of sites in these regions that were eventually selected for monitoring in the SDWS. Nonetheless, the lack of monitoring in some of the high acetochlor use areas is especially problematic for the SDWS where the lack of sampling of raw ( pre facility treatment) water at most locations makes it difficult to isolate the effects of site specific usage and vulnerability factors and water treatment processes on the observed residue levels.

° Acute exposure in this risk assessment is defined as the overall maximum observed concentration at a site. The actual peak concentration, however, may have occurred between sampling times. This study design, like the vast majority of surveys of surface waters for pesticide concentrations, is less well suited for estimating acute exposures than chronic exposures, especially in smaller and more rapidly flowing streams and rivers. However, the bias tends to be to underestimate, rather than overestimate to acute exposure levels ( because peak exposure durations may be much shorter than the sampling intervals). It was determined that exposure to acetochlor parent was significantly higher in the surface water monitoring sites than the ground water monitoring sites. The concentration used in the acute dietary Page 81 of 118 assessment was from a surface water monitoring site ( 214 GI IL) that produced the highest concentration of 0.01821 ppm ( M. Barrett, EFED Memorandum, pg. 41, 1/ 3/ 2005). The concentration used in the chronic dietary assessment was from a surface water monitoring site ( 214 GI IL) that produced the highest TWAM concentration for a single year ( M. Barrett, EFED Memorandum, pg. 13, 1/ 3/ 2005). The concentration used in the cancer dietary assessment was calculated from site 214 GI IL, which produced the highest overall multi year ( seven year) time weighted annualized mean concentration of 0.000287 ppm. Table 6.2 lists the top ten sites that produced the highest average TWAM values. It is noted, that site 214 GI IL produced the highest single concentration, the highest TWAM value for a single year, and the highest TWAM value that was averaged over the number of years the data was collected from the site.

Table 6.2 Highest Calculated Average TWAMs Using Data Provided by the ARP. The Highest TWAM Values for a Single Year along with the Highest Single Concentration are also Presented.

CWS Name Type Average TWAM Value ( ppm) No. of Years Highest TWAM Value for a Single Year ( ppm) Highest Single Concentration ( ppm)

214 GI IL Finished 0.0002871 7 0.001432 ( 1996) 0.01823 ( 5/ 15/ 1996)

330 LO IN Finished 0.000236 3 0.000418 ( 1997) 0.00735 ( 5/ 27/ 1997)

340 NV IN Finished 0.000208 2 0.000375 ( 1996) 0.00431 ( 5/ 28/ 1996)

168 PA IL Raw 0.000192 7 0.000591 ( 1998) 0.00719 ( 5/ 28/ 1998)

455 MO OH Finished 0.000179 7 0.000584 ( 1997) 0.0111 ( 5/ 27/ 1997)

451 ML OH Finished 0.000159 7 0.000281 ( 1997) 0.00356 ( 5/ 21/ 2001)

408 DE OH Finished 0.000154 5 0.000309 ( 1997) 0.00382 ( 5/ 5/ 1997)

157 MA IL Finished 0.000154 7 0.000461 ( 1996) 0.00793 ( 5/ 1/ 1996)

345 RI IN Raw 0.000144 3 0.000306 ( 1997) 0.00227 ( 6/ 4/ 1997)

518 US OH Finished 0.000137 7 0.000378 ( 1996) 0.00220 ( 5/ 20/ 1996)

1. This value, 0.000287 ppm, was used in the cancer dietary exposure assessment. 2. This value, 0.00143 ppm, was used in the chronic dietary exposure assessment 3. This value, 0.01821 ppm, was used in the acute dietary exposure assessment.

6.3 Residential ( Non Occupational) Exposure/ Risk Pathway Currently there are no registered residential uses for acetochlor, thus there is no exposure via this pathway.

7.0 Aggregate Risk Assessments and Risk Characterization In accordance with the FQPA, HED must consider and aggregate ( add) pesticide exposures and Page 82 of 118 risks from three major sources: food, drinking water, and residential exposures ( oral, dermal, and inhalation exposures). In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard ( e. g., a NOAEL or PAD), or the risks themselves can be aggregated. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure.

In general, exposures from various sources ( routes) are aggregated only when the toxic effects, determined by the endpoint selected for that route, are the same. In the present risk assessment no residential exposures need to be considered, since there are no registered residential uses for acetochlor. Thus the aggregate risks assessments include the contribution of risk from dietary ( food + drinking water) sources only. The results and specifics of these assessments are presented in Sections 6.1.2 and 6.2 reported in Table 6.1. Only the results of the assessments are reported in Sections 7.1  7.3 7.1 Acute Aggregate Risk This assessment concludes that for all supported registered commodities, the acute dietary risk estimates do not exceed HED's level of concern ( less than 100% of the aPAD) at the 99.9th exposure percentile for the U. S. population at 2% of the aPAD and all population subgroups, with the highest exposed population subgroup being infants less than 1 year old at 6% of the aPAD.

7.2 Short Term Aggregate Risk This scenario is not expected, since there are no residential uses.

7.3 Long Term Aggregate Risk This assessment concludes that for all supported registered commodities, the chronic dietary ( food + water) risk estimates do not exceed HED's level of concern ( less than 100% of the cPAD) for the U. S. population and all population subgroups ( all were less than 1% of the cPAD).

7.5 Cancer Risk The cancer dietary exposure assessment incorporated tolerance level residues for all crops and percent crop treated data provided by the ARP in MRID 45322101. Processing data were available for all commodities and incorporated into the assessment. The assessment also included the overall multi year time weighted annualized mean water concentration generated from the ARP acetochlor water monitoring program. The estimated exposure of the general U. S. population to acetochlor is 0.000026 mg/ kg/ day. Applying the Q 1 * of 3.27 x 10 2 ( mg/ kg/ day) 1 to the exposure value results in a cancer risk estimate of 8.40 x 10 7. Therefore, the cancer dietary risk estimate does not exceed HED's level of concern of 1.0 x 10 6. Page 83 of 118 8.0 Cumulative Risk Characterization/ Assessment Acetochlor is part of a Common Mechanism Group with the related chloroacetanilides butachlor and alachlor. See: Implementation of the Determination of a Common Mechanism of Toxicity for N Methyl Carbamate Pesticides and for Certain Chloroacetanilide Pesticides. Memorandum from M. M. Mulkey, Director, EPA/ OPP, dated July 12, 2001. A cumulative risk assessment is currently underway for acetochlor and alachlor. Butachlor is excluded because it is not registered in the US.

9.0 Occupational Exposure/ Risk Pathway This assessment supports the Tolerance Reassessment Eligibility Decision ( TRED) document for acetochlor and addresses exposures resulting from dietary ( food + drinking water) intakes only. Non occupational ( residential/ recreational) exposures do not need to be addressed in this document because acetochlor is not registered for residential/ recreational uses. Occupational exposures/ risks will not be addressed in this assessment.

10.0 Data Needs, Regulatory Recommendations, and/ or Label Requirements 10.1 Toxicology 1. A Developmental Neurotoxicity study is required. 2. Validation studies ( positive controls) should be submitted for the rat neurotoxicity studies.

10.2 Residue Chemistry 1. It has been determined that a permanent tolerance of 2.0 ppm be set for wheat hay based on the maximum residues of 0.457 ppm in wheat forage corrected for moisture content.

2. As the tolerances on field corn commodities are for the direct application to a primary crop, these general tolerances on corn should be reassigned to 40 CFR § 180.470( a). Likewise, tolerances on sorghum, soybeans, and wheat commodities are for inadvertent residues on rotational crops; therefore, these tolerances should be reassigned to 40 CFR § 180.470( d).

3. The available field trial data indicate that the current tolerances on corn grain and stover are adequate, but the tolerance on corn forage should be increased to 3.0 ppm based on data from the early post emergence use.

4. Labels allowing direct application to pop corn should be amended to prevent such application until the registrant formally petitions for the use. Page 84 of 118 References: RESIDUE CHEMISTRY Study Citations 00064797 Wilson, G. R.; Baszis, S. R.; Steinmetz, J. R.; et al. ( 1980) Residues of Acetochlor in Soybean and Corn Grain following Preemergent Treatment with Acetochlor Alone or in Tank mix Combinations with Atrazine, Linuron and Metribuzin: Report No. MSL 1242. Final rept. ( Unpublished study received Dec 12, 1980 under 524 EX 56; submitted by Monsanto Co., Washington, D. C.; CDL: 099813 A). 00085062 Malik, J. M. ( 1981) Acetochlor Crop Metabolism in Soybeans and Corn: Special Report MSL 1873. ( Unpublished study received Oct 27, 1981 under 524 EX 56; submitted by Monsanto Co., Washington, D. C.; CDL: 070434 A).

00106078 Monsanto Co. ( 1982) ? Residues of Acetochlor in Soybeans and Other Crops|. ( Compilation; unpublished study received Jul 14, 1982 under 2G2726; CDL: 070984 A).

00116632 Wilson, G.; Dubelman, S. ( 1982) Residue Determination of Acetochlor Metabolites in Hog Tissue: Report No. MSL 2286. Final rept. ( Unpublished study received Oct 21, 1982 under 524 EX 56; submitted by Monsanto Co., Washington, DC; CDL: 248621 A; 248622).

00116633 Wilson, G.; Dubelman, S. ( 1982) Residue Determination of Acetochlor Metabolites in Milk and Beef Tissues: Report No. MSL 2285. Final rept. ( Unpublished study received Oct 21, 1982 under 524 EX 56; prepared in corporation with Hazleton Raltech, Inc., submitted by Monsanto Co., Washington, DC; CDL: 248623 A; 248624).

00116634 Wilson, G.; Dubelman, S. ( 1982) Residue Determination of Acetochlor Metabolites in Eggs and Chicken Tissues: Report No. MSL 2287. Final rept. ( Unpublished study received Oct 21, 1982 under 524 EX 56; prepared in cooperation with Hazleton Raltech, Inc., submitted by Monsanto Co., Washington, DC; CDL: 248625 A; 248626).

00118950 Monsanto Co. ( 1982) ? Acetochlor: Residues in Goats|. ( Compilation; unpublished study received Nov 18, 1982 under 524 EX 56; CDL: 071246 A).

40365601 Oppenhuizen, M.; Wilson, G. ( 1987) Residues of Acetochlor from Two Metabolite Classes in Corn Forage, Corn Grain and Corn Fodder: Laboratory Project No. MSL 6843: R. D. No. 817. Unpublished study prepared by Monsanto Agricultural Co. 294 p.

40365602 Letendre, L.; Hooblen, M.; Wratten, S. ( 1987) Metabolism of Synthetic Plant Metabolites of Acetochlor in the Laying Hens: Laboratory Project No. MSL 6941: R. D. No. 818. Unpublished study pre pared by Monsanto Agricultural Co. 171 p.

40383401 Mueth, M. ( 1987) Acetochlor Residues from Two Metabolite Classes in Defeated Corn Page 85 of 118 Meal: Laboratory Project No. MSL 6835: R. D. No. 824. Unpublished study prepared by Monsanto Agricultural Co. 171 p.

40383402 Wilson, G. ( 1987) An Acetochlor Analytical Method Interference Study: Laboratory Project No. MSL 6900: R. D. No. 825. Unpublished study prepared by Monsanto Agricultural Co. 188 p.

40879201 Oppenhuizen, M. ( 1988) Additional Chromatograms Requested by the Agency in Support of Monsanto Report No. MSL 6843, " Residues of Acetochlor from Two Metabolite Classes in Corn Forage, Corn Grain and Corn Fodder", Volume Corn Grain: RD 895. Unpublished study prepared by Monsanto Agricultural Co. 212 p.

40879202 Oppenhuizen, M. ( 1988) Additional Chromatograms Requested by the Agency in Support of Monsanto Report No. MSL 6843, " Residues of Acetochlor from Two Metabolite Classes in Corn Forage, Corn Grain and Corn Fodder", Volume II Corn Forage: RD 895. Unpublished study prepared by Monsanto Agricultural Co. 207 p.

40879203 Oppenhuizen, M. ( 1988) Additional Chromatograms Requested by the Agency in Support of Monsanto Report No. MSL 6843, " Residues of Acetochlor from Two Metabolite Classes in Corn Forage, Corn Grain and Corn Fodder", Volume III Corn Fodder: RD 895. Unpublished study prepared by Monsanto Agricultural Co. 186 p.

40879204 Mueth, M. ( 1988) Additional Chromatograms Requested by the Agency in Support of Monsanto Report No. MSL 6835, " Acetochlor Residues from Two Metabolite Classes in Defeated Corn Meal": RD 895. Un published study prepared by Monsanto Agricultural Co. 170 p.

40965101 Oppenhuizen, M. ( 1989) Regulatory Enforcement Method for the Determination of Acetochlor Residues in Raw Agricultural Commodities: Laboratory Project No. MSL 8453: R. D. No. 908. Unpublished study prepared by Monsanto Agricultural Co. in cooperation with Craven Laboratories, Inc. 51 p.

40965102 Meuth, M. ( 1989) Regulatory Enforcement Method for the Determination of Acetochlor Residues in Beef Tissues and Milk: Laboratory Project No. MSL 8567: R. D. No. 908. Unpublished study prepared by Monsanto Agricultural Co. 36 p.

41304201 Lauer, R.; Mayonado, N. ( 1989) Acetochlor Residues from Two Metabolite Classes in Corn, Dry milled and Wet milled Processed Corn Fractions: Lab Project Number: MSL 8512: 965. Unpublished study prepared by Monsanto Agricultural Co. 301 p.

41304202 Oppenhuizen, M. ( 1989) Storage Stability of Two Classes of Acetochlor Metabolites in Corn Grain, Forage and Fodder: Lab Project Number: MSL 9043: 965. Unpublished study prepared by Monsanto Agricultural Co. 128 p. Page 86 of 118 41304203 Arras, D. ( 1989) Regulatory Enforcement Method for the Determination of Acetochlor Residues in Milk, Beef Tissues and Raw Agricultural Commodities: Lab Project Number: MSL 9572: 965. Unpublished study prepared by Monsanto Agricultural Co. 32 p.

41565156 Corden, M.; Skidmore, M. ( 1990) Acetochlor: Metabolism in Maize: Lab Project Number: 88JH439. Unpublished study prepared by ICI Agrochemicals. 127 p.

41565157 Hawkins, D.; Kirkpatrick, D.; Dean, G.; et al. ( 1989) Biokinetics and Metabolism of [ 14C] Acetochlor in the Goat: Lab Project Number: HRC/ STR 25/ 89412. Unpublished study prepared by Huntingdon Research Centre Ltd. 78 p.

41565158 Hawkins, D.; Kirkpatrick, D.; Dean, G.; et al. ( 1990) Biokinetics and Metabolism of ( 14C) Acetochlor in the Laying Hen: Lab Project Number: HRC/ STR 26/ 90147. Unpublished study prepared by Huntingdon Research Centre Ltd. 54 p.

41565159 Hand, L.; Skidmore, M. ( 1990) Acetochlor: Metabolism and Bio transformation in Hens: Lab Project Number: RJ0854B. Unpublished study prepared by ICI Agrochemicals. 87 p.

41565160 Zilka, S.; Simmons, N. ( 1990) Acetochlor: Residue Analytical Method Report for the Determination of 2 Chloro N( Ethoxymethyl) N 2 Ethyl 6 Methylphenyl) Acetamide in Field Corn: Grain, Cob, Fodder, Forage & Silage, Processed Corn and other Crops: Lab Project Number: RJ 0819B. Unpublished study prepared by ICI Agrochemicals. 30 p.

41565161 Crook, S.; Simmons, N. ( 1990) Acetochlor: Residue Analytical Method Report for the Determination: Lab Project Number: 5676 88 MR 01. Unpublished study prepared by ICI Agrochemicals. 26 p.

41565162 Simmons, N.; O'Brien, M. ( 1989) Acetochlor and R25788: Residues in Processed Corn Fractions from Trials Carried Out in the USA during 1988: Lab Project Number: 5676 88 PR 01. Unpublished study prepared by ICI Agrochemicals. 45 p.

41565163 Pay, J.; Gaunt, N.; Simmons, N. ( 1990) Acetochlor: Residues in Field Corn from Trials Carried Out in the USA during 1988: Lab Project Number: 5676 88 MR 01. Unpublished study prepared by ICI Agrochemicals. 116 p.

41592014 Crook, S.; Zilka, S.; Simmons, N. ( 1990) Acetochlor: Residues of 2 Ethyl 6 methylaniline ( E. M. A) Metabolites in Field Corn from Trials Carried Out in the USA during 1988: Lab Project Number: 5676 88 MR 01. Unpublished study prepared by ICI Agrochemicals. 116 p.

41633501 Arras, D. ( 1990) Regulatory Enforcement Method for the Determination of Acetochlor Residues in Milk, Beef Tissues, and Raw Agricultural Commodities: Lab Project Number: MSL 10380: 1008. Un published study prepared by Monsanto Agricultural Co., and Hazleton Page 87 of 118 Laboratories America, Inc. 148 p.

41633601 Cheng, T. ( 1990) Nature/ Magnitude of the Residue in Lactating Goats Preliminary and Definitive Phases: Lab Project Number: HLA 6103 116: 1009. Unpublished study prepared by Hazleton Laboratories America, Inc. 221 p.

41961201 Corden, M.; Skidmore, M. ( 1990) Acetochlor: Metabolism in Maize: Amendment/ Addendum: Lab Project Number: 88JH439. Unpublished study prepared by ICI Agrochemicals, Jeallott's Hill Research Station. 41 p.

41961202 Crook, S.; Simmons, N. ( 1990) Acetochlor: Residue Analytical Method Report for the Determination of 2 Ethyl 6 Methylaniline ( E. M. A) in Field Corn, Grain, Fodder and Forage Addendum: Lab Project Number: RJ0840B. Unpublished study prepared by ICI Agrochemicals, Jealott's Hill Research Station. 9 p.

41961203 Zilka, S.; Simmons, N. ( 1991) Acetochlor: Residue Analytical Method Report for the Determination of 2 Chloro N( Ethoxymethyl) N ( 2 Methyl 6 Methylphenyl) Acetamide in Field Corn: Grain, Cob, Fodder, Forage & Silage, Processed Corn and other Crops Addendum: Lab Project Number: RJ0819B. Unpublished study prepared by Agrochemicals, Jealott's Hill Research Station. 9 p.

41961204 Zilka, S.; Simmons, N. ( 1990) Acetochlor: Residue Analytical Method Report for the Determination of 2 Chloro N( Ethoxymethyl) N ( 2 Ethyl 6 Methylphenyl) Acetamide in Field Corn: Grain, Cob, Fodder, Forage & Silage, Processed Corn and Other Crops Amendment: Lab Project Number: RJ0819B. Unpublished study prepared by Agrochemicals, Jealott's Hill Research Station. 7 p.

41961205 Simmons, N.; O'Brien, M. ( 1989) Acetochlor and R25788: Residue in Processed Corn Fractions from Trials Carried Out in the USA During 1988: Addendum: Lab Project Number: 5676 88 PR 01: RJ0786B. Unpublished study prepared by ICI Agrochemicals, Jealott's Hill Research Station. 10 p.

41963322 Corden, M.; Mathis, S.; Skidmore, M. ( 1991) Acetochlor: Metabolism in Maize: Final Report: Lab Project Number: 88JH439. Unpublished study prepared by ICI Agrochemicals. 137 p.

41963323 Crook, S.; Downey, C.; Skidmore, M. ( 1991) Acetochlor: Accumulation and Biotransformation of Carbon 14 Acetochlor Plant Metabolites in Ruminants: Lab Project Number: 90JH345. Unpublished study prepared by ICI Agrochemicals. 189 p.

41963324 Crook, S.; Khundker, S.; Skidmore, M. ( 1991) Acetochlor: Accumulation and Biotransformation of [ 14C] Metabolites in Poultry: Lab Project Number: 91JH142. Unpublished study prepared by ICI Agrochemicals. 131 p. Page 88 of 118 41963325 Crook, S.; Simmons, N. ( 1991) Acetochlor: Residue Analytical Method Report for the Determination of 2 Ethyl 6 Methylaniline ( E. M. A.) and 2( 1 Hydroxyethyl) 6 Methylalanine ( H. E. M. A) in Field Corn; Grain; Fodder; Forage and Process Fractions. Unpublished study prepared by ICI Agrochemicals. 33 p.

41963326 Zilka, S.; Simmons, N. ( 1991) Acetochlor: Tolerance Enforcement Method Report for the Determination of 2 Chloro N( Ethoxymethyl) N( 2 Ethyl 6 Methylphenyl) Acetamide in Field Corn: Grain, Cob, Fodder, Forage and Processed Corn: Lab Project Number: 5676 88 MR 01. Unpublished study prepared by ICI Agrochemicals. 68 p.

41963327 Gillard, D. ( 1991) Analysis of Acetochlor by Multiresidue Methods FDA Pesticide Analytical Manuel Volume I: Lab Project Number: A030. 007D: 0021 CL ML 01. Unpublished study prepared by Huntingdon Analytical Services. 118 p.

41963328 Crook, S.; Wilson, B.; Simmons, N. ( 1991) Acetochlor: Residues of 2( 1 Hydroxyethyl) 6 Methylaniline ( H. E. M. A) Metabolites in Field Corn From Trials Carried Out in the U. S. A. During 1988: Lab Project Number: 5676 88 MR 01. Unpublished study prepared by ICI Agrochemicals. 129 p.

42549903 Powell, S.; Skidmore, M. ( 1991) Acetochlor: Quantification and Characterisation of Radioactive Residues in Tissues, Milk and Excreta of Goats after Oral Dosing with [ 14C] Acetochlor: Lab Project Number: 90JH195: RJ1019B. Unpublished study prepared by ICI Agrochemicals. 185 p.

42549904 Downey, C.; Skidmore, M. ( 1992) ICIA5676/ 57: Metabolism in Hens following Dosing at 10 ppm in the Diet: Lab Project Number: 91JH253: RJ1179B. Unpublished study prepared by ICI Agrochemicals. 111 p.

42549905 Corden, M.; Renwick, R.; Mathis, S.; et. al ( 1992) ICIA5676/ 57: Metabolism in Lactating Cow following Oral Dosing at 25 ppm in the Diet: Lab Project Number: 91JH220: RJ1228B. Unpublished study prepared by ICI Agrochemicals. 79 p.

42549908 Mannion, R.; Steinmetz, J. ( 1992) Storage Stability of Acetochlor Metabolites in Soybean, Wheat, and Sorghum Raw Agricultural Commodities: Lab Project Number: MSL 12139. Unpublished study prepared by Monsanto Company. 162 p.

42549909 Wilson, B.; Simmons, N. ( 1992) Acetochlor: Storage Stability of Residue in Deep Frozen Processed Corn Fractions: Lab Project Number: 89JH352: RJ1096B. Unpublished study prepared by ICI Agrochemicals. 60 p.

42549910 Simmons, N.; Crook, S. ( 1991) Acetochlor: Storage Stability of the EMA Acetochlor Metabolite Class in Deep Frozen Field Corn Fractions: Interim Report: Lab Project Number: 91JH307: RJ1060B. Unpublished study prepared by ICI Agrochemicals. 24 p. Page 89 of 118 42549911 Simmons, N.; Crook, S. ( 1991) Acetochlor: Storage Stability of the HEMA Acetochlor Metabolite Class in Deep Frozen Field Corn Fractions: Lab Project Number: 5676 88 MR 01: RJ1067B. Unpublished study prepared by ICI Agrochemicals. 23 p.

42549914 Kerregan, R.; Lau, P. ( 1992) Acetochlor Metabolite Residues in Processed Fractions from Soybeans as a Rotation Crop: Lab Project Number: MSL 12091: SARS 89 NC 92TP: SARS 89 NE 92P. Unpublished study prepared by Monsanto Company. 309 p.

42549919 O'Neal, S.; Johnson, T. ( 1992) A Confined Rotational Crop Study with [ 14C] Acetochlor using Radishes ( Raphanus sativus), Lettuce ( Lactuca sativa) and Wheat ( Triticum aestivum): Lab Project Number: MSL 12105: 474. Unpublished study prepared by PTRL East, Inc., Pharmacology & Toxicology Research Lab, and Plant Sciences, Inc. 377 p.

42591501 Sidhu, R. ( 1992) Acetochlor Metabolite Residues in Rotational Crops Following Preemergent Application of Acetochlor to Corn: Lab Project Number: MSL 11963 ( MONSANTO): 39084 ( ABC LABS): 40104 ( ABC LABS). Unpublished study prepared by Monsanto Co., ABC Laboratories, and Stewart Agricultural Research Services, Inc. 2845 p.

42713111 Lauer, R. ( 1991) Interference Determination of Metolachlor in Corn Forage, Fodder and Grain Following Preemergent Treatment with Acetochlor: Lab Project Number: MSL 10452: 1033. Unpublished study prepared by Monsanto Agricultural Company and ChemAlysis. 153 p.

42713112 Nash, R. ( 1991) Multiresidue Methodology Testing of CP 95200, CP 92429, CP 97290, CP 108669, CP 106070, and CP 106077 ( Acetochlor Metabolites): Lab Project Number: 11520: 115 008: 1033. Unpublished study prepared by EPL Bio Analytical Services, Inc. 170 p.

42713113 Ralph, C.; Veal, P.; French, D. ( 1992) Acetochlor: Residues of N( 6 Ethyl 3 Hydroxy 2 Methylphenyl) Oxamic Acid in Filed Corn from Trials Carried Out in the USA During 1991: Lab Project Number: ACET 91 MR 01: RJ1337B. Unpublished study prepared by ICI Agrochemicals. 40 p.

42713114 Johnson, T.; French, D.; Bathke, P.; et al. ( 1992) Acetochlor: Residues in Field Corn from Trials Carried Out in the USA During 1991: Lab Project Number: ACET 91 MR 01: RJ1321B. Unpublished study prepared by ICI Agrochemicals. 78 p.

42713115 Veal, P.; French, D. ( 1992) Acetochlor: Residues of 2 Ethyl 6 Methylaniline ( EMA) and 2( 1 Hydroxyethyl) 6 Methylaniline ( HEMA) in Field Corn from Trials Carried Out in the USA During 1991: Lab Project Number: ACET 91 MR 01: RJ1235B. Unpublished study prepared by ICI Agrochemicals. 241 p.

42713116 Crook, S. ( 1992) Acetochlor: Analytical Method for the Determination of N( 6 Ethil 3 Hydroxy 2 Methylphenyl) Oxamic Acid in Crops and Processed Corn Fractions: Lab Project Number: 92JH078: RJ1257B. Unpublished study prepared by ICI Agrochemicals. 25 p. Page 90 of 118 42713117 Crook, S. ( 1992) Acetochlor: Storage Stability of the N( 6 Ethil 3 Hydroxy 2 Methylphenyl) Oxamic Acid Metabolite in Deep Frozen Field Corn, Grain, Forage and Fodder: Interim Results: Lab Project Number: 91JH223: RJ1352B. Unpublished study prepared by ICI Agrochemicals. 25 p.

42831607 Lau, P. ( 1992) Residues of Acetochlor from two Metabolite Classes in Field Corn Following Preemergent Application of MON 8422: Lab Project Number: MSL 11794: HWI 6103 129: 0642 90 1. Unpublished study prepared by Monsanto Co., Hazleton Wisconsin, Inc. and Stewart Agricultural Research Services, Inc. 611 p.

42908601 Veal, P.; Bathke, P.; French, D. ( 1993) ACETOCHLOR: Residues of N( 6 ethyl 3 hydroxy 2 methylphenyl) Oxamic Acid in Processed Corn Fractions from a Trial Carried Out in the USA During 1991: ( Interim Report): Lab Project Number: ACET 91 PR 01: RJ1460B. Unpublished study prepared by ICI Agrochemicals. 49 p.

43266501 Veal, P.; French, D.; Johnson, T. et al. ( 1994) Acetochlor and ( inert ingredient) Residue Levels in Field Corn Following Treatment with two New Formulations: Lab Project Number: ACET 93 MR 01: RJ1591B. Unpublished study prepared by Zeneca Agrochemicals, Jealott's Hill Research Station. 128 p.

43470001 Arras, D. ( 1994) Regulatory Enforcement Method for the Determination of Acetochlor Residues in Milk, Beef Tissues, and Raw Agricultural Commodities: Reformatted Method: Lab Project Number: RES 074 93. Unpublished study prepared by Monsanto Environmental Science Dept. 34 p.

43616401 French, D.; Crook, S.; Veal, P.; et al. ( 1994) Acetochlor and ( inert ingredient): Magnitude of Residues in Field Corn Following Post Emergence Application ( USA 1993): Lab Project Number: RJ 1735B: ACET 93 MR 03: 94 IL 93 410. Unpublished study prepared by Zeneca Agrochemicals. 178 p.

43616402 Allan, J. ( 1994) Acetochlor Metabolite Residues in Field Corn Commodities Following Early Post emergent Applications of Acetochlor: Lab Project Number: MSL 13414: 41383: 93 27 R 2. Unpublished study prepared by Monsanto Co.; ABC Labs.; and Stewart Agricultural Research Services, Inc. 319 p. Page 91 of 118 Agency Memoranda Citations Table 9. Agency Memoranda Citations.

Date DP Barcode CB No. From To MRID Nos. Subject 6/ 2/ 81 None None J. Worthington R. Taylor Not listed PP# 1G2454. Acetochlor on Corn and Soybeans.

Evaluation of the Analytical Methods and Residue Data.

1/ 18/ 82 None None J. Worthington R. Taylor and Toxicology Branch Not listed PP# 1G2454. Acetochlor on Corn and Soybeans.

Comments on the amendment of 10/ 23/ 81.

10/ 28/ 82 None None S. Malak R. Taylor Not listed PP# 2G2726. Acetochlor on Corn, Soybeans, and Peanuts. Evaluation of Analytical Method and Residue Data.

6/ 6/ 83 None None S. Malak R. Taylor and Toxicology Branch Not listed PP# 3G2797 and PP# 2G2726. Acetochlor in Milk, Eggs,

and Tissues of Livestock. Evaluation of Analytical Method and Residue Data including Amendment of December 2, 1982 submitted in connection with PP# 2G2726.

7/ 20/ 84 None R. Cook PP# 3F2966. Memo was not available for review.

8/ 3/ 88 None 3894

3899,

3902 F. Griffith R. Taylor and C. Trichilo 40554801 40554804,

40365601, 40365602 PP# 3F2966 and PP# 6G3345  Acetochlor in Corn, Corn Products, Meat, Milk, Poultry, and Eggs. Evaluation of Amendments.

4/ 11/ 89 None M. Flood PP# 3F2966. Memo was not available for review.

8/ 7/ 90 None 6262,

6263 L. Cheng R. Taylor and Toxicology Branch 41304201 41304203,

41013201 41013206,

40994402 PP# 1G2454 & 524 EUP 56. Acetochlor on Field Corn.

Evaluation on Analytical Methods and Residue Data.

1/ 3/ 91 None 7035,

7131 L. Cheng J. Miller, and Toxicology Branch 41565150, 41565151,

41565155 41565163,

41592014 PP# 0G3888 & 10182 EUP LU. Acetochlor on Field Corn. Evaluation of Analytical Methods and Residue Data. Table 9. Agency Memoranda Citations.

Date DP Barcode CB No. From To MRID Nos. Subject Page 92 of 118 4/ 29/ 91 D156740 7118 7121 N. Dodd R. Taylor, and Toxicology Branch 41633500, 41633501,

41633601 PP# 3F2966/ 1G2454. Acetochlor no Corn, Corn Products, Meat, Milk, Poultry, and Eggs. Amendment dated 9/ 20/ 90.

10/ 28/ 91 D167686,

D167690 8423,

8454 L. Cheng J. Miller, and J. Mayes 41961201 41961205 PP# 0G3888 & 10182 EUP LU. Acetochlor on Field Corn. Response to 1/ 3/ 91 Review. Waiver Request on Feeding Studies.

7/ 12/ 93 D187729, D187731, D187733, D190315, D190317, D190320,

D190322 11330

11332, 11747

11750 M. Flood R. Taylor,

V. Walters,

A. Kocialski, and S. Willett 41963322 41963328,

42549903 42549905,

42549909, 42549912,

42713111 42713117 PP# 3F2966/ PP# 1F4011, Acetochlor Registration Partnership. Acetochlor EC Herbicide for Use on Field Corn.

8/ 23/ 93 D189047, D187729, D187731,

D187733 11330

11332, 11540,

11541 M. Flood R Taylor and V.

Walters 42549908, 42549914,

42549919, 42591501 PP# 3F2966/ PP# 1F4011. Acetochlor Registration Partnership. Acetochlor EC Herbicide for Use on Field Corn. Confined Rotational Crop Study. Field Rotational Crop Studies.

9/ 30/ 93 None None M. Flood Metabolism Committee, HED None The Metabolism Committee Meeting Held on September 15, 1993. Plant and Animal Metabolism of Acetochlor.

11/ 24/ 93 D194327

D194329, D195035, D195036,

D196269 12417

12419, 12539,

12540 M. Flood R. Taylor,

V. Walters,

A. Kocialski, and S. Willett 42908601 PP# 3F2966/ PP# 1F4011. Acetochlor Registration Partnership. Acetochlor EC Herbicide for Use on Field Corn. Response to CBTS Memo Dated 7/ 12/ 93.

1/ 11/ 94 D197597, D197599, D197601

D197605 12974

12980 M. Flood R. Taylor,

V. Walters,

A. Kocialski, and S. Willett None PP# 3F4232   Acetochlor, Rotational Crop Tolerances.

Amendment Dated 12/ 13/ 93 from Acetochlor Registration Partnership ( ARP). Table 9. Agency Memoranda Citations.

Date DP Barcode CB No. From To MRID Nos. Subject Page 93 of 118 8/ 1/ 94 D196581 12774 M. Flood R Taylor and V.

Walters 42831607 Acetochlor   Microencapsulated Formulation.

Evaluation of Residue Data. ID#. 00524 UTR MON

8421.

2/ 6/ 95 D210066 14851 M. Flood R Taylor and V.

Walters 43470001 Acetochlor. ID#: 066478 00002. Reformatted Analytical Method.

4/ 14/ 95 D204673 13896 S. Willet R Taylor and V.

Walters 43266501 ID No. 10182 GOR. ICIA 6576 3.2 CS Herbicide ( a. i.

acetochlor w/ the safener dichlormid). New Formulation of Use on Field Corn and Popcorn.

6/ 25/ 96 D214735,

D214738 None G. Herndon,

W. Dykstra,

and C. Lewis V. Walters and R. Taylor 43616401 PP# 5F4505. Section 3 Registration and Permanent Tolerance Petition to Expand the Use of Acetochlor End

Use Products to Include Postemergence Application to Corn.

10/ 25/ 96 D229611 None S. Willett D. McCall None PP No. 5F4505. Acetochlor ( Chemical No. 121601) on Corn. Revised Label and Section F in Response to 6/ 25/ 96 RCAB/ PIRAT Review. Page 94 of 118 HAZARD CHARACTERIZATION 00050928 Ahmed, F. E., Tegeris, A. S., Underwood, P. C. et al. ( 1980) CP 55097: 119 Day Study in the Dog. Pharmacopathics Research Laboratories, Inc., Laurel, MD. Lab Report No. 7920 ( Sponsor's Report No. 79 114), October 10, 1980. Unpublished report.

00050929 Rodwell, D. E. and McMeekin, S. O. ( 1980) Teratology Study in Rats IR 79 009. International Research and Development Corp., Mattawan, MI. Laboratory Report No. IRDC 401 066. October 15, 1980. Unpublished report.

00050930 Ross, W. D. and Kulik, F. A. ( 1978) Salmonella Mutagenicity Assay of CP 55097, DA 78 186: Monsanto Co. Study Report No. MRC DA 838. Unpublished report.

00050933 Ahmed, F. E., Seely, J. C., Tegeris, A. S. et al. ( 1980) CP 55097: 91 Day Feeding Study in the Rat. Pharmacopathics Research Laboratories, Inc., Laurel, MD. Report No. 7914. October 10, 1980. Unpublished report.

00116631 Ahmed, F. E. ( 1981) A One Year Feeding Study in Dogs with MON 097. Pharmacopathics Research Laboratories, Laurel, MD. Study No. 8006 ( Sponsor Report No. PR 80 008), October 14, 1981. Unpublished report.

00116637 Johnson, D. E. ( 1981) 21 Day Dermal Toxicity Study in Rabbits. International Research and Development Corp., Mattawan, MI. Study no. IR 80 356, December 11, 1981. Unpublished report.

00118944 Branch, D., Stout, L. and Folk, R. ( 1982) Primary Skin Irritation of MON 097 to Rabbits. Environmental Health Laboratory, St. Louis, MO, Study EHL 820031. October 18, 1982. Unpublished report.

00118945 Branch, D. K., Stout, L. D. and Folk, R. M. ( 1982) Acute Dermal Toxicity of MON 097 to Rabbits. Environmental Health Laboratory, St. Louis, MO. Study No. 820032. Unpublished report.

00118946 Branch, D. K., Stout, L. D. and Folk, R. M. ( 1982) Primary Skin Irritation of MON 097 to Rabbits. Environmental Health Laboratory, St. Louis, MO. Study No. 820033, October 18, 1982. Unpublished report.

00118947 Branch, D. K., Stout, L. D. and Folk, R. M. ( 1982) Primary Eye Irritation of MON 097 to Rabbits. Environmental Health Laboratory, St. Louis, MO. Study No. 820034, October 18, 1982. Unpublished report. Page 95 of 118 00130839 Carr, K., Elliott, R., Halasinski, K. et al. ( 1983) The Metabolism of Acetochlor in the Laboratory Rat. Hazleton Raltech Inc., Laboratory Report No. MSL 2824, June 1, 1983. Unpublished report.

00131088 Ahmed, F. E. and Seely, J. C. ( 1983) Acetochlor: Chronic Feeding Toxicity and Oncogenicity Study in the Rat. Pharmacopathics Research Laboratories, Inc., Laurel, MD. Study No. PR 80 006. May 20, 1983. Unpublished report.

00131089 Ahmed, F. E., Tegeris, A. S. and Seely, J. C. ( 1983) MON 097: 24 Month Oncogenicity Study in the Mouse. Pharmacopathics Research Laboratories, Inc., Laurel, MD. Report No. PR 80 007. May 4, 1983. Unpublished report.

00131391 Schardein, J. Marroquin, F and Thorstenson, J. ( 1982) Two Generation Reproduction Study in Rats: MON 097. International Research and Development Corp., Mattawan, MI. Study No. IR 80 053, December 16, 1982. Unpublished report.

00131392 Farrow, M. G. and Cortina, T. ( 1983) In Vivo Bone Marrow Chromosome Study in Rats with Acetochlor ( MON 097). Hazleton Laboratories, Study No. HL83 006 ( Hazleton Project No. 241 143), May 24, 1983. Unpublished report.

00131393 Naismith, R. W. and Mathews, R. ( 1983) Rat Hepatocyte Primary Culture/ DNA Repair Test. Pharmakon Research International, Inc., Waverly, PA. Monsanto Study No. PK 82 151 ( Pharmakon Project No. PH 311 MO 001 82), February 18, 1983. Unpublished report.

00131394 Mitchell, A. D., Rudd, C. and Coleman, R. ( 1983) An Evaluation of Mutagenic Potential of MON 097 Employing the L5178Y Tk +/ Mouse Lymphoma Assay. SRI International, Menlo Park, CA. Study No. SR 81 150 ( Project No. LSC 2575), August 1, 1982. Unpublished report.

00131395 Li, A. P., Rice, T., Folk, R. et al. ( 1983) CHO/ HGPRT Gene Mutation Assay with Mon 097. Monsanto Environmental Health Laboratory. Study No. ML 82 281; Project No. EHL 830013, June 9, 1983. Unpublished report.