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 provided with the cover letter for this submission. 

Acetochlor; 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), Registration Division (750C), 

Office of pesticide programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW, 

Washington, DC 20450-0001; telephone number: (703) 308-9364; e-mail address: 

Tompkins.Jim@epa.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 East, 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'-

ethyl-N-ethoxymethylacetanilide) and its metabolites containing either the 2-ethyl-6-

methylaniline (EMA) or the 2-(1-hydroxyethyl)-6- methyl-aniline (HEMA) moiety, to be

expressed as acetochlor equivalents, in or on the following 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 0.03 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 fully evaluated the 

sufficiency of the submitted data at this time or whether the data supports granting of the 

petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry
1. Plant Metabolism. The metabolism of acetochlor has been studied in cotton, corn, 

soybeans, sorghum and peanuts. Acetochlor metabolizes extensively to yield a complex array of 

polar metabolites. The major metabolic pathways 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 glutathione and subsequent 

catabolism. EPA has determined that the tolerance expression contain parent and metabolites 

hydrolyzed to EMA and HEMA. 

2. Analytical method. An adequate enforcement method for residues of acetochlor in 

crops has been approved. Acetochlor and its metabolites are hydrolyzed 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 eye irritation. Two dermal irritation studies are 

available. Severe irritation resulting in a classification of Toxicity Category II was observed in a 

study conducted with an obsolete source of technical acetochlor while only minimal irritation 

resulting in a Toxicity Category IV 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 been 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 lymphoma gene mutation assay. Acetochlor 

also exhibited a weakly positive response in the first of two Chinese hamster ovary

hypoxanthine-guanine phosphoribosyltransferase (CHO/HGPRT) gene mutation assays but was 

clearly negative in a subsequent CHO/HGPRT assay. Acetochlor was clastogenic at cytotoxic 

dose levels in an in vitro cytogenetics assay in human lymphocytes. However, no evidence of 

clastogenicity or other genotoxic effect was observed in a number of in vivo assays, including a 

rat bone marrow chromosomal aberration assay, two mouse micronucleus assays and dominant 

lethal mutation assays in rats and mice. No evidence of DNA damage was noted in an in vitro

unscheduled DNA synthesis (UDS) assay in rat hepatocytes. A weakly positive response was 

noted in an in vivo rat hepatocyte UDS assay, but only at an excessively 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 weeks of dietary exposure to acetochlor.

The clastogenic effect observed with acetochlor in vitro has been shown to be a result of 

the reactive chloroacetyl moiety and is most evident under test conditions where glutathione 

concentrations are low. This effect has not been observed under in vivo conditions where higher 

glutathione levels result in the protective binding of acetochlor to glutathione instead of the SHgroups of chromatin and other critical cellular proteins. Thus, the overall weight of evidence 

indicates that the positive responses observed with acetochlor in some in vitro studies are not 
relevant 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 clinical 

pathology parameters and in liver and kidney weights but these were not associated with any 

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 body 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. Slightly increased serum ALT activity in males and slightly 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 10 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 conducted with both rats and 

rabbits. The NOAEL for systemic effects in rabbits was 400 mg/kg/day based on mortality and 

decreased body weight at 1,200 mg/kg/day. No signs of systemic toxicity were noted in rats at 

dose levels up to 100 mg/kg/day (HDT). 

4. Chronic toxicity and oncogenicity. Two one-year 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. Slightly decreased food consumption, markedly decreased body 

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 any 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 parameters, macroscopic lesions in a number of organs, and histopathological 

changes in the brain, kidneys 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. 

Histopathological changes in the kidneys were also observed at 10 mg/kg/day. No treatmentrelated 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.

Three 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 Tolerated Dose 

(MTD) for acetochlor in rats is approximately 1000 ppm (54 mg/kg/day). The primary
indications 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 thyroid 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 only at 

5000 ppm, a dose level which greatly exceeded the MTD, and is thus not considered relevant for 

human risk 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 thyroid and nasal tumors observed in the chronic rat feeding studies with acetochlor. 

These studies have demonstrated that both tumors are produced non-genotoxic, thresholdmediated mechanisms to which the rat is especially sensitive. The thyroid tumors are caused by

induction of a liver enzyme, UDP-glucuronyltransferase (UDPGT), that results in decreased 

levels of thyroid hormone and a compensatory increase in thyroid stimulating hormone (TSH), 

which acts upon the rat thyroid to induce hyperplasia and ultimately neoplasia. This is a wellknown mechanism in rats that is widely believed to have little or no relevance to humans. The 

nasal tumors result from the formation of reactive iminoquinone metabolites by the rat olfactory

tissue. These metabolites bind to the cysteine residues in nasal proteins and cause oxidative 

stress. The resulting cytotoxicity and regenerative cell proliferation, if sustained, eventually 

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, particularly at anticipated levels of exposure. 

Two 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 noted 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 significant. 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 (approximately 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 only at a dose level that greatly exceeded the MTD. Slightly increased incidences of 

lung tumors and histiocytic 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 only minimal potential to induce reproductive or developmental toxicity, and such 

effects occur only in the presence of significant 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 dose 
levels 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 was 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 study, 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 by 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 for 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 any 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 (particularly during the latter portion of lactation) 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 body weights and a slight decrease in pup weights 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 any 

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 

ppm. 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 observed in adult animals at 

1750 and 600 ppm included decreased body weights; increased liver, kidney and/or thyroid 

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 delayed vaginal opening was attributed to the delay in reaching critical body

weight, and not a specific developmental 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 200 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 system 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 statistically significant decrease in motor 

activity was also noted one day after dosing in females at 500 mg/kg. However, this was not 
considered 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 by 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 consumption were 

observed at 1750 ppm but no evidence of neurotoxicity was observed at any dose level. The 

NOAEL for this study was 600 ppm (approximately 52 mg/kg/day). 

7. Animal metabolism. Numerous in vivo studies have been conducted to evaluate the 

absorption, distribution, metabolism and/or excretion of acetochlor in rats, mice, monkeys, goats 

and hens. In addition, the metabolism of acetochlor has also been evaluated in vitro using liver 

and nasal tissues from rats, mice and monkeys, and nasal tissues 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, particularly 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 by 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 acetochlor. Furthermore, they

do not produce the preneoplastic changes responsible for the rat nasal and thyroid tumors that 

occur with parent acetochlor, and thus are unlikely to be carcinogenic. Consequently, the EPA 

has concluded that the ESA and OXA metabolites 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 

system has been observed. As previously noted, acetochlor did produce a secondary effect on 

thyroid hormone homeostasis at high dose levels in rats as a result of induction of the hepatic 

enzyme UDPGT. However, this is a relatively common finding in rats that is generally thought 

to have little to no relevance to human risk assessment, particularly at the low doses to which 

humans are likely to be exposed. Similarly, the observation of delayed vaginal opening at the 

high-dose level in the most recent reproduction study is also considered to be a secondary effect 

resulting 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 corn, 

sweet corn, pop corn, cotton, sorghum, and soybeans. 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 soybeans, and tolerances for indirect or inadvertent residues 
have 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 

soybean); potato; sunflower seed; and animal 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 exposures were estimated by EPA when the Agency

established new tolerances for cotton and soybeans (16 September 2009, 74 FR 47445), acting 

on tolerance petitions PP 8F7443 and PP 8F7448 submitted by Monsanto Company The acute 

dietary analysis was based on tolerance 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 analysis included 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 all other processed commodities. The 

present analysis 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 exposure 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 residues 

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 DEEM-FCIDTM analysis 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 systemic toxicity, even after repeated dermal exposures. Thus, potential risks from 

non-occupational, non-dietary exposure 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 family of herbicides that also produces nasal olfactory and thyroid follicular 

tumors in rats. Mechanistic studies indicate that these two chemicals share common modes of 

action for both the nasal and thyroid tumors. However, the EPA and FIFRA Scientific Advisory

Panel have concluded that the thyroid tumors are not an appropriate endpoint for cumulative risk 
assessment for acetanilides because increased incidences of these tumors were marginal and/or 

occurred only at high dose levels, and were produced via a well-known, non-genotoxic 

mechanism to which the rat is especially sensitive. Therefore, a cumulative risk assessment for 

combined residues of alachlor and acetochlor should be based only 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 population subgroups 

were assessed using an acute RfD of 0.15 mg/kg. This was based on a NOAEL of 150 mg/kg 

from the acute rat neurotoxicity study and a 1000-fold uncertainty 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/day which was derived from a NOAEL of 2.0 mg/kg/day

from the second one-year dog study and a 100-fold uncertainty factor. No additional database or 

FQPA uncertainty factor was utilized for the chronic risk assessment since the Agency 

concluded that the NOAEL from a DNT study would be greater than the NOAEL from the oneyear 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” and 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 point 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 cancer 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 tumors from combined exposures to alachlor 

and acetochlor. For the cumulative risk assessment, acetochlor was assumed to have 1/20th the 

relative potency of alachlor based on unequivocal oncogenic NOELs of 10 and 0.5 mg/kg/day, 

respectively. 

2. Acute Exposure and Risk. Based on the above assumptions, the current and proposed 

uses of acetochlor would result in estimated 95th 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/day for 

all infants, the most highly exposed population subgroup. These exposures represent <1% and 

approximately 3.6% of the aPAD, respectively. In general, exposures utilizing less than 100% of 

the aPAD are not of concern. Therefore, there is a reasonable 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 overall US population to acetochlor is estimated to be 1.3 x 10-4
mg/kg/day. This represents <1% of the cPAD. Chronic dietary exposure to all infants (<1 year 

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 certainty that 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 Q1*; 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 quantitative 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 1/20th of alachlor. Acceptable 

MOEs in that analysis, and the lack of any increase in exposure based on this petition result in a 

reasonable certainty that dietary exposures to the combined residues of alachlor and acetochlor 

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 Levels established for residues of acetochlor on 

agricultural commodities.