Monsanto Company, member and managing agent of The Acetochlor Registration

Partnership, authorizes the EPA to publish the following summary of the petition to comply with the Food Quality Protection Act of 1996. An electronic copy on computer disc is provi ded with the cover letter for this submission. Ac etochlor; Notice of Filing a Pesticide Petition to Establish a Tolerance for Inadvertent Residues in or on Peanut Pesticide Petition: PP 0F7703 Registration Division Contact : James A. Tompkins (PM 25), R egistration Division (750C), Office of pesticide programs, Environmental Protection Agency , 1200 Pennsy lvania Ave., NW, Washington, DC 20450

- 0001; telephone number: (703) 308

- 9364; e

- mail address: Tompkins.Jim@ep a.gov . * * * * * * * * * * * * * * Summary

of Petition A summary

of the pesticide petition is printed below as required by section 408(d)(3) of the FFDCA. The petition summary was prepared by

the Petitioner and represents the views of the Petitioner. The summary announces the need to establish a rotational crop tolerance for acetochlor in peanuts

. Monsanto Company Pesticide Petition (PP) 0F7703 EPA has received a pesticide petition ( PP 0F7703 ) from Monsanto Company , 1300 I Street NW, Suite 450 Eas t, Washington DC 2005, a member of the Acetochlor Registration Partnership, ARP) proposing pursuant to section 408(d) of the Federal Food, Drug and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR Part 180.470 (d) ( Indirect or inadvertent residues ) by establishing a new tolerance for the residues of acetochlor (2

- chloro

- 2'

- methyl

- 6'

- ethy l

-N

- ethox ym ethy lacetanilide) and its metabolites containing either the 2

- ethy l

- 6

- methy laniline (EMA) or the 2

- (1

- hy drox ye thyl)

- 6

- methy l

- aniline (HEMA) moiety , to be expressed as acetochlor equivalents, in or on the follow ing raw agricultural commodity when present therein as a result of the application of acetochlor to the growing crops in paragraph (a) of 40 CFR Part 180.470 : peanut at 0 .0 3 ppm. EPA has determined that the petition contains data or information regarding the elements set forth in section 408(d)(2) of the FFDCA; however, EPA has not full y evaluated the sufficiency

of the submitted data at this time or whether the data supports granting of the petitio n. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry1. Plant Metabolism . The metabolism of acetochlor has been studied in cotton, corn,

soy beans , sorghum and peanuts . Acetochlor metabolizes extensively to yield a comp lex array

of polar metabolites. The major metabolic pathway s are: (i) uptake of soil metabolites and subsequent metabolism, (ii) uptake of acetochlor followed by oxidative metabolism and conjugation, and (iii) uptake of acetochlor, conjugation with glutath ione and subsequent catabolism. EPA has determined that the tolerance expression contain parent and metabolites hy drol yz ed to EMA and HEMA. 2. Analytical method . An adequate enforcement method for residues of acetochlor in crops has been approved. Ace tochlor and its metabolites are hy drol yz ed to either EMA or HEMA, which are determined by HPLC

- OCED and expressed as acetochlor equivalents. 3. Magnitude of the residues . Residue trials with applications to corn and with peanuts as a rotational crop in the following season show that the proposed tolerance will not be exceeded when acetochlor is used as directed

. B. Toxicological Profile 1. Acute toxicity . The EPA has classified technical acetochlor as toxicity category III for acute oral, dermal and inhalation toxicity , and ey e irritation. Two dermal irritation studies are available. Severe irritation resulting in a classification of Toxicity Category I I was observed in a study conducted with an obsolete source of technical acetochlor while onl y mi nimal irritation resulting in a Toxicity

Category I V classification was noted with a higher purity test material that is more representative of current technical material. Acetochlor is known to be a skin sensitizer. 2. Genotoxicity . Acetochlor has bee n evaluated in an extensive battery of in vitro and in vivo genotoxicity

studies. Acetochlor was not mutagenic in the Ames Salmonella assay but exhibited a weakly

positive response in a mouse ly mphoma gene mutation assay . Acetochlor also exhibited a weak ly

positive response in the first of two Chinese hamster ovary hy poxanthine

- guanine phosphoribosy ltransferase (CHO/HGPRT) gene mutation assay s but was clearl y negative in a subsequent CHO/HGPRT assay . Acetochlor was clastogenic at cy totoxic dose levels in an in vitro cy togenetics assay

in human ly

mphocy tes. However, no evidence of clastogenicity

or other genotoxic effect was observed in a number of in vivo assay s, including a rat bone marrow chromosomal aberration assay , two mouse micronucleus assay s and dominant lethal mutation assay s in rats and mice. No evidence of DNA damage was noted in an in vitro unscheduled DNA sy

nthesis (UDS) assay

in rat hepatocy

tes. A weakl y positive response was noted in an in vivo rat hepatocy te UDS assay , but only

at an exc essively

high dose level associated with marked hepatotoxicity and mortality . Furthermore, no evidence of DNA damage was observed in rat nasal olfactory cells (the primary

oncogenic target site for acetochlor) using gel electrophoresis following 1 or 18 w eeks of dietary exposure to acetochlor. The clastogenic effect observed with acetochlor in vitro has been shown to be a result of the reactive chloroacet yl moiety and is most evident under test conditions where glutathione concentrations are low. This ef fect has not been observed under in vivo conditions where higher glutathione levels result in the protective binding of acetochlor to glutathione instead of the SH

groups of chromatin and other critical cellular proteins. Thus, the overall weight of evide nce indicates that the positive responses observed with acetochlor in some in vitro studies are notrelevant in vivo and that acetochlor would not pose a significant risk of genotoxicity to humans under anticipated conditions of exposure. 3. Sub

- chronic toxicity . Two 90

- day rat feeding studies have been conducted, at dietary concentrations ranging from 20 to 6000 ppm. The primary effects observed in these studies were decreased weight gain and food consumption. Minor changes were noted in several clin ical pathology parameters and in liver and kidney weights but these were not associated with an y histopathological changes. The overall No Observable Adverse Effect Level (NOAEL) for both studies combined was 200 ppm (approximately 18 mg/kg/day). Two sub

- chronic dog studies were conducted in which acetochlor was administered via capsule at dose levels ranging from 2 to 200 mg/kg/day . In a 119

- day study , excessive toxicity , including emaciation, decreased bod y weight and a high rate of mortality, was noted at 200 mg/kg/day . Changes in several clinical pathology parameters, increased organ weights and histopathological lesions of the liver, kidney and bone marrow were observed at 200 and 75 mg/kg/day . Slightl y increased serum ALT activity in males and slightl y increased relative liver weights in females were also noted at 25 mg/kg/day , the lowest dose tested. However, due to lack of corroborative clinical pathology and/or histopathological findings, these were not considered to be indicative of a treatment

- related adverse effect. In a 90

- day study , decreased body weight gain, clinical signs of toxicity , clinical pathology changes and increases in relative liver weight were noted at 60 mg/kg/day , the highest dose tested (HDT). No effects were observed at 1 0 mg/kg/day , the next lowest dose level. Thus, based on the results of both studies combined, 25 mg/kg/day

is considered to be the overall NOAEL for sub

- chronic toxicity of acetochlor in dogs. Sub

- chronic (21

- day) dermal toxicity studies have been conduc ted with both rats and rabbits. The NOAEL for sy stemic effects in rabbits was 400 mg/kg/day based on mortality

and decreased bod y weight at 1,200 mg/kg/day . No signs of sy stemic toxicity were noted in rats at dose levels up to 100 mg/kg/day (HDT). 4. Chronic toxicity and oncogenicity . Two one

- ye ar dog studies have been conducted with acetochlor. In the first study , dogs were administered acetochlor via capsule at dose levels of 0, 4, 12, and 40 mg/kg/day . Slightl y decreased food consumption, marked ly decreased bod y weight gain, testicular atrophy and some indications of liver toxicity were observed at 40 mg/kg/day . A possible indication of liver toxicity was also noted in one animal at 12 mg/kg/day but no effects on an y parameter were noted at 4 mg/kg/day . In a second study , dogs were administered acetochlor via capsule at dose levels of 0, 2, 10, and 50 mg/kg/day . Excessive toxicity (including weight loss, emaciation, clinical signs of toxicity , alterations in a number of clinical pathology

param eters, macroscopic lesions in a number of organs, and histopathological changes in the brain, kidney s and testes) was evident at 50 mg/kg/day and resulted in the premature sacrifice (post week 39) of a number of high

- dose animals for humane reasons. Histo pathological changes in the kidney s were also observed at 10 mg/kg/day . No treatment

related effects were noted at 2 mg/kg/day . Thus, based on both studies, the overall NOAEL for chronic toxicity

of acetochlor in dogs is considered to be 4 mg/kg/day

. Thre e chronic rat feeding studies have been conducted with acetochlor, at dietary concentrations ranging from 18 to 5000 ppm (approximately 0.8 to 297 mg/kg/day

for both sexes combined). The overall results from the three studies indicate that the Maximum Tol erated Dose (MTD) for acetochlor in rats is approximately 1000 ppm (54 mg/kg/day). The primaryindications of toxicity at this level were decreased body weights, mild liver effects (as evidenced by increased liver weights and clinical pathology changes) and kidney

lesions. Increased incidences of nasal olfactory and thy roid follicular tumors were observed at dose levels greater than or equal to 1000 ppm. The EPA also considered a single nasal tumor at 500 ppm in one study to be treatment related, although a single nasal tumor was also observed in a control animal from a subsequent acetochlor study . An increased incidence of liver tumors occurred onl y at 5000 ppm, a dose level which greatl y exceeded the MTD, and is thus not considered relevant for human r isk assessment. Based on all 3 studies, the overall NOAEL for chronic toxicity in the rat was considered to be 200 ppm (approximately 10 mg/kg/day). This dose level was also considered to be the unequivocal NOEL for oncogenicity

. A number of mechanistic studies have been conducted to determine the mode of action for the th yroid and nasal tumors observed in the chronic rat feeding studies with acetochlor. These studies have demonstrated that both tumors are produced non

- genotoxic, threshold

mediated mechanisms to which the rat is especially sensitive. The thy

roid tumors are caused by induction of a liver enz yme, UDP

- glucuron yl transferase (UDPGT ) , that results in decreased levels of thy

roid hormone and a compensatory increase in th yroid stimulating hormone (TSH), which acts upon the rat thy roid to induce h yp erplasia and ultimately neoplasia. This is a well

known mechanism in rats that is widely believed to have little or no relevance to humans. The nasal tumors result from the formation of reactive iminoq uinone metabolites by

the rat olfactory tissue. These metabolites bind to the cy steine residues in nasal proteins and cause oxidative stress. The resulting cy

totoxicity and regenerative cell proliferation, if sustained, eventuall y results in formation of olfactory tumors. However, large species differences at several steps in the production of the reactive quinoneimine metabolites indicate that this mode of action would be unlikely

to occur in humans, particularl y at anticipated levels of exposure. Tw o mouse oncogenicity studies have been conducted with acetochlor, at dietary concentrations ranging from 10 to 5000 ppm (approximately 1.2 to 973 mg/kg/day). Increased mortality , decreased weight gain, anemia and signs of kidney and liver toxicity

were no ted at 1500 and 5000 ppm. Renal toxicity and anemia were also noted at 1000 ppm (approximately 126 mg/kg/day), which was considered to be the MTD. Some minor differences from controls were noted at 100 ppm but were not considered to be toxicologically si gnificant. Thus, the ARP concluded that 100 ppm (approximately 12 mg/kg/day) was the NOAEL for mice. The EPA, however, considered the slight differences at 100 ppm to be indicative of a treatment

- related adverse effect and concluded that 10 ppm (approxim ately 1.1 mg/kg/day) was the NOAEL. A treatment

- related increased incidence of liver tumors was noted in male mice at 5000 ppm. However, these tumors were not considered relevant for human risk assessment since they occurred onl y at a dose level that gre atly exceeded the MTD. Slightly increased incidences of lung tumors and histiocy

tic sarcomas were also noted. However, these tumors were considered unrelated to treatment by panels of independent expert pathologists and of only equivocal relationship to treatment by the EPA. 5. Reproductive and developmental toxicity . Studies in rats and rabbits indicate that acetochlor has onl y minimal potential to induce reproductive or developmental toxicity , and such effects occur only

in the presence of signifi cant maternal toxicity . No evidence of increased sensitivity

to offspring was noted in either species. Two rat developmental toxicity studies have been conducted, at dose levels ranging from 40 to 600 mg/kg/day . In the first study , rats were administered acetochlor by gavage at doselevels of 0, 50, 200, and 400 mg/kg/day . Decreased maternal weight gain and clinical signs of

toxicity were observed at 400 mg/kg/day . A slight decrease in mean fetal weights was also noted at 400 mg/kg/day . However, this w as not considered to be treatment

- related because the difference was not statistically significant and the mean value was well within the historical control range. EPA, however, disagreed and has concluded that this was evidence of developmental toxicity

. In a second stud y, rats were administered acetochlor at dose levels of 0, 40, 150, and 600 mg/kg/day . Both maternal and fetal toxicity were observed at 600 mg/kg/day , as evidenced b y animals sacrificed moribund, clinical observations, decreased maternal weight gain, increased post

- implantation loss and decreased fetal weight. No maternal or developmental effects were noted at 150 mg/kg/day . Thus, based on the results from both studies combined, the ARP considers 200 mg/kg/day to be the overall NOAEL fo r maternal toxicity and 400 mg/kg/day

to be the overall NOAEL for developmental toxicity

. Two rabbit developmental toxicity studies have been conducted, at dose levels ranging from 15 to 300 mg/kg/day. No developmental toxicity was noted at an y dose level . The overall NOAEL for maternal toxicity was 100 mg/kg/day

based on decreased weight gain at 190 mg/kg/day , and decreased weight gain and mortality at 300 mg/kg/day

. Three multi

- generation rat reproduction studies have been completed, at dietary concentrations ranging from 18 to 5000 ppm. In the first study , acetochlor was administered at dietary concentrations of 0, 500, 1500 and 5000 ppm. Decreased numbers of live pups at birth and decreased pup weights (particularl y during the latter portion of lact ation) were observed at 5000 ppm. However, this level also induced excessive parental toxicity as indicated by substantially

decreased body

weights (up to 33% in females) and kidney lesions. Decreased parental bod y weights and a slight decrease in pup we ights were also noted at 1500 ppm. Based on these results, 500 ppm (approximately 30 to 46 mg/kg/day) was considered to be the NOAEL for both parental and offspring toxicity . In a second study , acetochlor was administered at dose levels of 0, 18, 175 and 1750 ppm. No effect on reproductive performance was noted at an y dose level. Decreased body weights, slightly

reduced food consumption and increased relative organ weights in parents, and decreased pup weight gain during lactation, were noted at 1750 pp m. Thus, 175 ppm (approximately 13 to 18 mg/kg/day) was considered to be the NOAEL for both parental and offspring toxicity . In the most recent study , acetochlor was administered to rats at dietary

concentrations of 0, 200, 600 and 1750 ppm. Effects obs erved in adult animals at 1750 and 600 ppm included decreased bod y weights; increased liver, kidney and/or th yr oid weights; and histopathological changes (including benign tumors) of the nasal olfactory epithelium. Decreased pup weights were noted at both 600 and 1750 ppm. Decreased numbers of uterine implantations and a delay in vaginal opening in F1 pups were also noted at 1750 ppm. However, the delay ed vaginal opening was attributed to the delay in reaching critical body weight, and not a specific dev elopmental effect, since the body weight of the 1750 ppm pups at time of vaginal opening was comparable to that of controls. Based on these results, 600 ppm (approximately

57 to 71 mg/kg/day) was considered to be the NOAEL for reproductive effects while 2 00 ppm (approximately 19 to 22 mg/kg/day) was the NOAEL for overall toxicity

. 6. Neurotoxicity. No evidence of a direct or specific effect on the nervous sy stem was observed in acute and sub

- chronic neurotoxicity studies conducted in the rat. In the acute study , acetochlor produced general signs of toxicity , including mortality and transient changes in motor activity , following a single oral dose of 1500 mg/kg. A statisticall y significant decrease in motor activity was also noted one day

after dosin g in females at 500 mg/kg. However, this was notconsidered to be treatment related because the activity level of these animals was higher than prior to dosing and there was no change in habituation. Therefore, 500 mg/kg/day was considered b y the ARP to be the NOAEL. EPA, however, has concluded that the NOAEL for this study was 150 mg/kg/day

. In the sub

- chronic study , acetochlor was administered to rats for 13 weeks at dietary concentrations of 0, 200, 600 and 1750 ppm. Decreased weight gain and food c onsumption were observed at 1750 ppm but no evidence of neurotoxicity was observed at an y dose level. The NOAEL for this stud y was 600 ppm (approximately 52 mg/kg/day). 7. Animal metabolism . Numerous in vivo studies have been conducted to evaluate th e absorption, distribution, metabolism and/or excretion of acetochlor in rats, mice, monkey s, goats and hens. In addition, the metabolism of acetochlor has also been evaluated in vitro using liver and nasal tissues from rats, mice and monkey s, and nasal t issues in humans. These studies have shown that acetochlor is well absorbed following oral administration and is extensively metabolized and rapidly

excreted. No major sex differences were noted. However, significant species differences were observed, p articularl y with respect to the formation and distribution of the metabolite(s) believed responsible for the occurrence of nasal tumors in the rat. 8. Metabolite toxicology . A number of studies have been conducted to evaluate the potential effects that may be associated with the t

- ethane sulfonic (ESA) and t

- oxanilic (OXA) acid metabolites of acetochlor. These are environmental degradates that are formed b y soil microbes and have been detected in ground and surface water. These metabolites are highly polar and water soluble, and lack the reactive chlorine of parent acetochlor. The results from the toxicology

studies indicate that acetochlor ESA and OXA are more poorly absorbed, more rapidly excreted and exhibit a lower degree of toxicity than parent a cetochlor. Furthermore, they do not produce the preneoplastic changes responsible for the rat nasal and thy roid tumors that occur with parent acetochlor, and thus are unlikely to be carcinogenic. Consequently , the EPA has concluded that the ESA and OXA m etabolites should not be included in the acute, chronic or cancer risk assessments for acetochlor. 9. Endocrine disruption . No evidence of a direct effect of acetochlor on the endocrine sy stem has been observed. As previously noted, acetochlor did pro duce a secondary effect on thy roid hormone homeostasis at high dose levels in rats as a result of induction of the hepatic enzy me UDPGT. However, this is a relativel y common finding in rats that is generall y thought to have little to no relevance to human risk assessment, particularl y at the low doses to which humans are likel y to be exposed. Similarly , the observation of delay ed vaginal opening at the high

- dose level in the most recent reproduction study is also considered to be a secondary effect result ing from decreased body weight gain in the pups. Neither of these findings is considered to pose a significant concern for human risk assessment. C. Aggregate Exposure 1. Dietary exposure

- Food. Acetochlor is currently registered for use on field cor n, sweet corn, pop corn , cotton, sorghum , and so yb eans . Tolerances for acetochlor and/or its metabolites containing the EMA or HEMA moieties have been established for field corn, sweet corn, pop corn , cotton, sorghum, and soy beans, and tolerances for indi rect or inadvertent residueshave been established for the rotational crops : wheat; cereal grains, group 16 (except corn, grain

sorghum, rice and wheat); sugar beet; pea and bean, dried shelled, subgroup 6C (except soy bean); potato; sunflower seed; and ani mal feed, nongrass, group 18. No tolerances have been established for livestock commodities because there is no reasonable expectation of finite residues based on the results of exaggerated rate feeding studies. Potential acute and chronic dietary exposur es were estimated by EPA when the Agency established new tolerances for cotton and so yb eans (16 September 2009, 74 FR 47445), acting on tolerance petitions PP 8F7443 and PP 8F7448 submitted by Monsanto Company The acute dietary anal ys is was based on toler ance level residues and 100% crop treated assumptions for all commodities. Experimentally derived processing factors were used for cereal grain commodities. Default values were used for all other processed commodities. The chronic dietary anal ys is incl uded anticipated residues from field trial data and 100% crop treated assumptions for all commodities. Experimentally derived processing factors were used for cereal grain commodities. Default values were used for al l other processed commodities. The pr esent analy sis incorporated these same assumptions. 2. Dietary exposure

- Water. The ARP has conducted extensive monitoring of surface and ground water for residues of acetochlor and has included the results of these studies in the overall dietary

expos ure assessment using the DEEM

- FCID software. These monitoring data were collected in corn

- growing areas during a period of high use of acetochlor. Therefore, these monitoring data are appropriate for characterizing potential ground and surface water resi dues from the proposed use of acetochlor as described in this petition. The drinking water values used in the dietary

risk assessment were based on information provided by the ARP water monitoring program. Exposure to acetochlor parent was significantly higher in the surface water monitoring sites than in the ground water monitoring sites; therefore, the concentration used in the acute dietary assessment was from a surface water monitoring site that produced the highest concentration of 0.01821 ppm. The concentration used in the chronic dietary assessment was from a surface water monitoring site that produced the highest time

- weighted annualized mean (TWAM) concentration for a single year of 0.00143 ppm. Water residues were incorporated in the D EEM

- FCIDTM analy sis into the food categories “water, direct, all sources” and “water, indirect, all sources”. 3. Non

-Dietary Exposure . There are no residential or non

- agricultural uses of acetochlor. Therefore, non

- dietary , non - occupational exposure to acetochlor is expected to be negligible. In addition, 21

- day dermal toxicity

studies with acetochlor indicate a very low potential for sy stemic toxicity , even after repeated dermal exposures. Thus, potential risks from non - occupational, non

- dietary expos ure to acetochlor are considered to be negligible and were not included within the aggregate risk assessment. D. Cumulative Effects Acetochlor is a close structural analog of alachlor, another member of the chloroacetanilide famil y of herbicides that al so produces nasal olfactory and thy roid follicular tumors in rats. Mechanistic studies indicate that these two chemicals share common modes of action for both the nasal and thy roid tumors. However, the EPA and FIFRA Scientific Advisory Panel have conclu ded that the thy roid tumors are not an appropriate endpoint for cumulative riskassessment for acetanilides because increased incidences of these tumors were marginal and/or

occurred onl y at high dose levels, and were produced via a well

- known, non

- genotox ic mechanism to which the rat is especiall y sensitive. Therefore, a cumulative risk assessment for combined residues of alachlor and acetochlor should be based onl y on the potential for formation of nasal olfactory

tumors. E. Safety Determination 1. Endpoint Selection . Potential acute and chronic risks from exposure to acetochlor were determined using the toxicology endpoints utilized by

EPA in the March 2006 Tolerance Reassessment Eligibility

Decision (TRED) document. Acute risks for all populati on subgroups were assessed using an acute RfD of 0.15 mg/kg. This was based on a NOAELof 150 mg/kg from the acute rat neurotoxicity study and a 1000

- fold uncertaint y factor. Although no evidence of increased sensitivity

to offspring was noted in rats or rabbits following in utero and/or postnatal exposure, the EPA applied an additional 10X database uncertainty factor due to the lack of a developmental neurotoxicity (DNT) study . Chronic (non

- cancer) risks were assessed using a chronic RfD of 0.02 mg/kg/d ay which was derived from a NOAEL of 2.0 mg/kg/day from the second one

- ye ar dog stud y and a 100

- fold uncertaint y factor. No additional database or FQPA uncertaint y factor was utilized for the chronic risk assessment since the Agency concluded that the NOA ELfrom a DNT study would be greater than the NOAEL from the one

ye ar dog study

and would thus not impact the risk assessment. In January

2007, the EPA revised the cancer classification of acetochlor to “Suggestive Evidence of Carcinogenic Potential” an d concluded that the potential carcinogenic risks should be evaluated using a non

- linear, margin

- of

- exposure (MOE) approach. A point of departure of 10 mg/kg/day , based on the unequivocal NOEL for rat nasal tumors, was identified as the most sensitive poi nt of departure for evaluating cancer risk. However, the Agency did not conduct a specific aggregate cancer risk assessment for acetochlor since the chronic RfD, which is based on a NOAEL of 2 mg/kg/day , would be protective against both non

- cancer and can cer effects. Nevertheless, a specific aggregate cancer risk assessment for acetochlor based on the 10 mg/kg/day

point of departure is presented here. In addition, a cumulative risk assessment was also conducted to assess the potential risks for nasal tum ors from combined exposures to alachlor and acetochlor. For the cumulative risk assessment, acetochlor was assumed to have 1/20 th the relative potency

of alachlor based on unequivocal oncogenic NOELs of 10 and 0.5 mg/kg/day , respectivel y. 2. Acute E

xposure and Risk. Based on the above assumptions, the current and proposed uses of acetochlor would result in estimated 95 th percentile acute dietary (food and water) exposures of 1.45 x 10 - 3 mg/kg/day for the overall US population and 5.32 x 10 - 3 mg/kg/d ay for all infants, the most highly exposed population subgroup. These exposures represent <1% and approximately

3.6% of the aPAD, respectivel y. In general, exposures utilizing less than 100% of the aPAD are not of concern. Therefore, there is a reason able certainty that acute dietary exposure to acetochlor will not pose a significant risk to human health, including infants and children. 3. Chronic Exposure and Risk. Based on the above assumptions, chronic dietary (food and water) exposure of the ove rall US population to acetochlor is estimated to be 1.3 x 10 - 4mg/kg/day . This represents <1% of the cPAD. Chronic dietary exposure to all infants (<1 y ear old), the most highly

exposed population subgroup, is estimated to be 2.8 x 10 - 4 mg/kg/day , which represents about 1.4% of the cPAD. Both of these values are well below 100% of the cPAD. Therefore, there is a reasonable certaint y t hat dietary (food and water) exposure to acetochlor will not pose a significant risk of chronic toxicity to the US population, including infants and children. 4. Cancer Risk

. (i

) Acetochlor: HED has determined that it is no longer appropriate to regulate cancer risk for acetochlor using a Q 1 *; however, nasal tumors in the rat, for which a mode of action has been identified , remain as a tumor of concern for human exposure. The chronic RfD, which is based on a NOAEL of 2 mg/kg/day , is considered to be protective of the nasal tumors, for which a point of departure of 10 mg/kg/day was identified. Therefore, a separate quantit ative cancer risk assessment is not required. (ii) Cumulative: The current cumulative risk assessment for the chloroacetanilides (Protzel et al., March 8, 2006, EPA Memorandum) notes that alachlor is the index chemical and acetochlor is included in the assessment with a relative potency 1/20 th of alachlor. Acceptable MOEs in that analy sis, and the lack of an y increase in exposure based on this petition result in a reasonable certainty

that dietary

exposures to the combined residues of alachlor and aceto chlor will not pose a significant risk of cancer. 5. Overall Conclusion of Safety. Based on the data summarized herein, there is a reasonable certainty

that no harm will result to the US population, including infants and children, from the current and proposed uses of acetochlor. F. International Tolerance There are no Codex Maximum Residue L evels established for residues of acetochlor on agricultural commodities.