EPA REGISTRATION DIVISION - COMPANY NOTICE OF FILING OF PESTICIDE 

PETITION

EPA Registration Division contact: Sidney Jackson (703) 305-7610

Interregional Research Project Number 4 (IR-4)

Pesticide Petition Number: 4E8239

EPA has received a pesticide petition (4E8239) from the Interregional Research Project 4 

(IR-4), IR-4 Headquarters, Rutgers, The State University of NJ, 500 College Road East, Suite 

201 W, Princeton, NJ 08540 requesting, 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 to establish 

tolerances for combined residues of the herbicide sethoxydim, 2-[1-(ethoxyimino)butyl]-5-[2-

(ethylthio)propyl]-3-hydroxy-2-cyclohexen-1-one (CAS Reg. No. 74051–80–2), and its 

metabolites containing the 2-cyclohexen-1-one moiety (calculated as the herbicide)] in or on the 

following raw agricultural commodities: Berry, low growing, subgroup 13-07H, except 

strawberry at 2.5 parts per million (ppm), Bushberry, subgroup 13-07B at 5.0 ppm; Caneberry

subgroup 13-07A at 5.0 ppm, Fescue, forage at 6.0 ppm; Fescue, hay at 4.0 ppm; Fruit, citrus, 

group 10-10 at 0.5 ppm; Fruit, pome, group 11-10 at 0.2 ppm; Fruit, small, vine climbing, 

subgroup 13-07F, except fuzzy kiwifruit at 1.0 ppm; Rapeseed subgroup 20A at 35 ppm; 

Sunflower subgroup 20B, except safflower, seed at 7.0 ppm; Cottonseed subgroup 20C at 5.0;

Vegetable, bulb, group 3-07 at 1.0 ppm; and Vegetable, fruiting, group 8-10 at 4.0 ppm. In

addition, IR-4 is proposing that upon approval of the above petitioned-for tolerances, established 

sethoxydim tolerances in or on the following commodities are removed, including: Blueberry at 

4.0 ppm; Borage, seed at 6.0 ppm; Caneberry subgroup 13A at 5.0 ppm; Canola, seed at 35.0 

ppm; Cotton, undelinted seed at 5.0 ppm; Crambe, seed at 35.0 ppm; Cranberry at 2.5 ppm; 

Cuphea, seed at 35.0 ppm; Echium, seed at 35.0 ppm; Flax, seed at 5.0 ppm; Fruit, citrus, group 

10 at 0.5 ppm; Fruit, pome, group 11 at 0.2 ppm; Gold of pleasure, seed at 35.0 ppm; Grape at 

1.0 ppm; Hare’s ear mustard, seed at 35.0 ppm; Juneberry at 5.0 ppm; Lesquerella, seed at 35.0 

ppm; Lingonberry at 5.0 ppm; Lunaria, seed at 35.0 ppm; Meadowfoam, seed at 35.0 ppm; 

Milkweed, seed at 35.0 ppm; Mustard, seed at 35.0 ppm; Oil radish, seed at 35.0 ppm; Poppy, 

seed at 35.0 ppm; Rapeseed, seed at 35.0 ppm; Salal at 5.0 ppm; Sesame, seed at 35.0 ppm; 

Sunflower, seed at 7.0 ppm; Sweet rocket, seed at 35.0 ppm; Vegetable, bulb, group 3 at 1.0 

ppm; and Vegetable, fruiting, group 8 at 4.0 ppm.

EPA has determined that the petition contains data or information regarding the elements 

set forth in section 408 (d)(2) of FDDCA; 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 qualitative nature of the residues in plants and animals 
is adequately understood for the purposes of registration.

2. Analytical method. Analytical methods for detecting levels of sethoxydim and 

its metabolites in or on food with a limit of detection that allows monitoring of food with 

residues at or above the level in these tolerances were submitted to EPA. The proposed 

analytical method involves extraction, partition, and clean-up. Samples are then analyzed by gas 

chromatography with sulfur-specific flame photometric detection. The limit of quantitation is 

0.05 ppm.

3. Magnitude of residues. IR-4 received a request from the Agricultural 

Experiment Stations of Oregon and Idaho for the minor use of sethoxydim on fine fescue 

(Creeping Red (Festuca rubra), Chewings (Festuca nigrescens), and Hard Fescue (Festuca 

ovina)) for the control of annual and perennial grasses in fine fescue grass grown for seed. The 

nature of the residues of sethoxydim is adequately understood and an acceptable analytical 

method is available for enforcement purposes. The registration of this use would provide the 

growers with a safe and effective herbicide for the control of annual and perennial grasses, yet 

would not expose human beings or the environment to unreasonable adverse effects. Therefore, 

tolerances are proposed for fescue, forage at 6.0 ppm and fescue, hay at 4.0 ppm based on the 

OECD tolerance calculator.

IR-4 received a request from the Agricultural Experiment Station of Oregon and North Carolina 

for the minor use of sethoxydim on blueberry (highbush and lowbush) for the control of grass 

weeds and to reduce the pre-harvest interval from 30 days to 1 day. The nature of the residues of 

sethoxydim is adequately understood and an acceptable analytical method is available for 

enforcement purposes. The registration of this use would provide the growers with a safe and 

effective herbicide for the control of grasses, yet would not expose human beings or the 

environment to unreasonable adverse effects. There is an existing blueberry tolerance of 4.0 

ppm for sethoxydim with a 30 day PHI. Based on the results of that study, IR-4 proposes the 

removal of the tolerance for blueberry (representative crop for the Bushberry subgroup 13-07B), 

Juneberry, Lingonberry and Salal and the establishment of a subgroup tolerance for the 

Bushberry subgroup 13-07B at 5.0 ppm. IR-4 proposes to change the pre-harvest interval for 

highbush blueberry to 1 day, while leaving the lowbush pre-harvest interval at 30 days.

In addition, IR-4 proposes the establishment of tolerances for the following revised crop groups 

based on existing tolerances that are shown in brackets:

 Caneberry subgroup 13-07A [Caneberry subgroup 13A at 5.0 ppm];

 Berry, low growing, subgroup 13-07G [Strawberry at 10 ppm];

 Berry, low growing, subgroup 13-07H, except strawberry [Cranberry at 2.5 ppm];

 Fruit, citrus, group 10-10 [Fruit, citrus, group 10 at 0.5 ppm];

 Fruit, pome, group 11-10 [Fruit, pome, group 11 at 0.2 ppm];

 Fruit, small, vine climbing, subgroup 13-07F, except fuzzy kiwifruit [Grape at 1.0 ppm];

 Rapeseed subgroup 20A [Borage, seed at 6.0 ppm; Canola, seed at 35.0 ppm; Crambe, 

seed at 35.0 ppm; Cuphea, seed at 35.0 ppm; Echium, seed at 35.0 ppm; Flax, seed at 5.0 
ppm; Gold of pleasure, seed at 35.0 ppm; Hare’s ear mustard, seed at 35.0 ppm; 

Lesquerella, seed at 35.0 ppm; Lunaria, seed at 35.0 ppm; Meadowfoam, seed at 35.0 

ppm; Milkweed, seed at 35.0 ppm; Mustard, seed at 35.0 ppm; Oil radish, seed at 35.0 

ppm; Poppy, seed at 35.0 ppm; Rapeseed, seed at 35.0 ppm; Sesame, seed at 35.0 ppm; 

and Sweet rocket, seed at 35.0 ppm];

 Sunflower subgroup 20B, except safflower [Sunflower, seed at 7.0 ppm];

 Cottonseed subgroup 20C [Cotton, undelinted seed at 5.0];

 Vegetable, bulb, group 3-07 [Vegetable, bulb, group 3 at 1.0 ppm]; and

 Vegetable, fruiting, group 8-10 [Vegetable, fruiting, group 8 at 4.0 ppm].]

B. Toxicological Profile

1. Acute toxicity. Sethoxydim has favorable acute toxicity. The acute toxicity

studies place technical sethoxydim in toxicity category III for acute oral, dermal and inhalation 

toxicity. Sethoxydim is category IV for both eye and skin irritation, and it is not a dermal 

sensitizer.

2. Genotoxicty. Sethoxydim was negative for inducing mutations in both an in 

vitro Ames test and an in vitro mammalian cell mutation assay. Sethoxydim also demonstrated 

no chromosomal effects in an in vivo sister chromatid exchange (Chinese hamster bone marrow) 

assay. An additional in vitro study investigating unscheduled DNA synthesis showed no effects. 

In total, sethoxydim has been tested in five genetic toxicology assays consisting of in vitro and in 

vivo studies. It can be stated that sethoxydim did not show any mutagenic, clastogenic or other

genotoxic activity when tested under the conditions of the studies mentioned above. Therefore, 

sethoxydim does not pose a genotoxic hazard to humans.

3. Reproductive and developmental toxicity. The reproductive and developmental 

toxicity of sethoxydim was investigated in a 2-generation rat reproduction study as well as in rat 

and rabbit developmental toxicity studies. In the reproduction study, a decreased pup body 

weight and tail abnormalities were observed at the highest dose tested. There were no effects on 

reproduction or evidence of parental toxicity. The NOAEL is >150 mg/kg bw/day for 

reproductive toxicity and 30 mg/kg bw/day for developmental toxicity.

In the rat study, maternal toxicity observed at the two highest doses consisted of some clinical 

signs including irregular gait and decreased activity. Developmental changes were also noted at 

the two highest doses and consisted of decreased fetal weights, tail abnormalities and skeletal 

variations. The maternal and developmental NOAEL’s were 180 mg/kg bw/day.

In the rabbit teratology study, maternal toxicity observed at high dose consisted of decreased 

food consumption and body weight gain. An increased incidence of incompletely ossified 6th

sternebrae was the only sign of developmental toxicity. The NOAEL for both maternal and 

developmental toxicity was 320 mg/kg bw.
4. Subchronic toxicity. The subchronic toxicity of sethoxydim was investigated in 

90-day feeding studies with rats and mice, a six-month feeding study in dogs and a 21-day

dermal administration study in rats and a 4-week inhalation study in rats. Generally, mild 

toxicity was observed. At high dose levels in feeding studies, general findings were decreased 

food consumption and body weight gain and liver changes indicative of an adaptive response to 

treatment. In addition, hemosiderosis of the spleen was observed at the highest dose tested in 

dogs. The lowest NOAEL in the subchronic feeding studies was 20 mg/kg bw/day in the 90-day

dog study.

In the 21-day repeat dose dermal study, no systemic effects were noted up to the highest dose 

tested of 1000 mg/kg bw/day. The 4-week inhalation toxicity study had a NOEC of 0.3 mg/l 

based on increased liver weight, clinical chemistry and liver histopathology at 2.4 mg/l.

5. Chronic toxicity. The NOAEL in the chronic dog study was 17.5 mg/kg 

bw/day based on effects observed at the high dose consisting of increased hemosiderosis in the 

spleen and depressed myeloid erythropoiesis in the sternal bone marrow, increased absolute and 

relative liver weights and increased serum liver enzymes.

In a rat chronic/oncogenicity study, sethoxydim was administered at doses up to 143 mg/kg 

bw/day in males and 204 mg/kg bw/day in females. Body weight gain decreases and liver 

toxicity in the form of hepatocellular hypertrophy were observed at the higher doses tested. The 

NOAEL’s for the chronic/oncogenicity study in rats were 12 mg/kg bw/day in males and 66 

mg/kg bw/day in females. There was no evidence of carcinogenicity in rats.

Sethoxydim was also tested for oncogenic potential in mice. Body weight gains were decreased 

in both sexes at the high dose. In addition, liver toxicity occurred at the two highest doses tested 

in males. This included an early onset of liver effects including hepatocellular hypertrophy and 

fatty degeneration. The NOAEL’s are 13.8 mg/kg bw/day for males and 44 mg/kg bw/day for 

females. There was no evidence that sethoxydim produced a carcinogenic effect in mice.

6. Animal metabolism. In a rat metabolism study with sethoxydim, excretion was 

shown to be extremely rapid and tissue accumulation was negligible. Of the administered dose, 

78% was excreted in urine and 20.1% in feces. Sethoxydim is extensively metabolized with very

little excretion of parent.

7. Metabolite toxicology. The most abundant plant metabolites for sethoxydim are 

hydroxy derivatives. Additional toxicology studies were conducted on 5-OH-MSO2, as a 

surrogate for all hydroxy metabolites. Based on these data, it was concluded that the 

toxicological potency of the plant hydroxy metabolites is likely to be equal to or less than that of 

the parent compound.

8. Endocrine disruption. No specific tests have been conducted with sethoxydim 

to determine whether the chemical may have an effect in humans that is similar to an effect 

produced by a naturally occurring estrogen or other endocrine effects. However, there were no 
significant findings in other relevant toxicity studies (i.e., subchronic and chronic toxicity, 

teratology and multi-generation reproductive studies) which would suggest that sethoxydim 

produces endocrine-related effects.

C. Aggregate Exposure

1. Dietary exposure. A dietary assessment was conducted to evaluate the 

potential risk due to acute and chronic exposure. The sethoxydim chronic reference dose (cRfD) 

is 0.14 mg/kg bw/day based on the NOAEL of 14 mg/kg bw/day and a 100X safety factor. The 

acute reference dose (aRfD) is 1.8 mg/kg bw/day for all populations including females of child 

bearing age, based on a NOAEL of 180 mg/kg bw/day and a 100X safety factor.

The analysis included all current tolerance values for sethoxydim listed in U.S. 40 CFR § 

180.412 with the proposed changes in this notification.

The proposed new tolerances are for Fescue, forage at 6.0 ppm and Fescue, hay.

The proposed revised crop group tolerances based on existing tolerances are:

1) Bushberry subgroup 13-07B at 5.0 ppm to replace blueberry, juneberry, lingonberry, and 

salal

2) Caneberry subgroup 13-07A at 5.0 ppm to replace Caneberry subgroup 13A

3) Berry, low growing, subgroup 13-07G at 10 ppm to replace strawberry

4) Berry, low growing, subgroup 13-07H, except strawberry, at 2.5 ppm to replace 

Cranberry

5) Fruit, citrus, group 10-10 at 0.5 ppm to replace Fruit, citrus, group 10

6) Fruit, pome, group 11-10 at 0.2 ppm to replace Fruit, pome, group 11

7) Fruit, small, vine climbing, subgroup 13-07F, except fuzzy kiwifruit, at 1.0 ppm to 

replace Grape

8) Rapeseed subgroup 20A at 35 ppm to replace Borage, seed; Canola, seed; Crambe, seed; 

Cuphea, seed; Echium, seed; Flax, seed; Gold of pleasure, seed; Hare’s ear mustard, seed; 

Lesquerella, seed; Lunaria, seed; Meadowfoam, seed; Milkweed, seed; Mustard, seed; 

Oil radish, seed; Poppy, seed; Rapeseed, seed; Sesame, seed; and Sweet rocket, seed 

9) Sunflower subgroup 20B, except safflower, seed at 7.0 ppm to replace Sunflower, seed

10) Cottonseed subgroup 20C at 5.0 ppm to replace Cotton, undelinted seed

11) Vegetable, bulb, group 3-07 at 1.0 ppm to replace Vegetable, bulb, group 3

12) Vegetable, fruiting, group 8-10 at 4.0 ppm to replace vegetable, fruiting, group 8.

i. Food. Acute Dietary Exposure Assessment

An acute dietary assessment was conducted using tolerance level residues, 100% crop treatment 

factors, and default processing factors for all commodities.

Using the exposure assumptions discussed above, the acute dietary exposure from food is 6.4% 

aPAD for the US population. The most highly exposed sub-population was children 1-2 years 
olds which utilized 14.4% of the aPAD. The results of the acute dietary assessment are 

presented in Table 1.

Table 1. Results for Sethoxydim Acute Dietary Exposure 

Analysis Including both Food and Drinking Water.

Population

Subgroups

95th Percentile 

Exposure Estimate

(mg/kg bw/day)

%aPAD

US Population 0.115813 6.4

All infants (< 1 year) 0.207434 11.5

Children 1-2 0.258563 14.4

Children 3-5 0.223652 12.4

Children 6-12 0.140949 7.8

Youth 13-19 0.085054 4.7

Adults 20-49 0.082702 4.6

Adults 50+ yrs 0.078437 4.4

Females 13 - 49 yrs 0.082104 4.6

Chronic Dietary Exposure Assessment

The chronic population adjusted dose (cPAD) used for US and all sub-populations is 0.14 mg/kg 

bw/day. Using the exposure assumptions discussed above, sethoxydim chronic dietary exposure 

from food for the US population was 31.9% of the cPAD. The most highly exposure 

subpopulation was children 1 - 2 years old which utilized 94.4% cPAD. The results of the 

chronic dietary assessment are presented in Table 2.

Table 2. Summary of Chronic Dietary Exposure 

Assessment Considering Crops with Established and 

Proposed Tolerances for Sethoxydim and Drinking Water.

Population

Subgroups

Exposure Estimate

(mg/kg bw/day) %cPAD

US Population 0.044671 31.9

All infants (< 1 year) 0.093969 67.1

Children 1-2 0.132143 94.4

Children 3-5 0.105162 75.1

Children 6-12 0.063504 45.4

Youth 13-19 0.036358 26.0

Adults 20-49 0.035444 25.3

Adults 50+ yrs 0.035608 25.4

Females 13 - 49 yrs 0.035204 25.1

]
ii. Drinking water. The drinking water values used in this assessment were based 

on the EPA document “Sethoxydim Drinking Water Assessment (Tier 1) for Reregistration 

Eligibility Decision” February 7, 2005. The estimated drinking water concentrations (EDWCs) 

for total sethoxydim residues are 1.5 ppb for ground water and 130 ppb (acute) and 16 ppb 

(chronic) for surface water. These water concentration where included in the dietary assessment 

conducted above.

Acute Aggregate Exposure and Risk (Food and water)

The aggregate acute risk includes residues of sethoxydim from food and water. Exposures from 

residential uses are not included in the acute aggregate assessment. Table 1 above shows the 

aggregate assessment for sethoxydim.

Chronic Aggregate Exposure and Risk (food and water)

The aggregate chronic risk includes residues of sethoxydim from food and water. Exposures 

from residential uses are not included in the chronic aggregate assessment. Table 2 above shows 

the aggregate exposure from food and water.

Short- and Intermediate Term Aggregate Exposure and Risk (Food, Water and Residential 

Exposure)

Short- and intermediate-term aggregate exposure takes into account residential exposure plus 

chronic exposure from food and water. Sethoxydim is only used for spot treatment in residential 

environments. The EPA has stated that exposure from spot treatment is negligible and a 

exposure risk assessment is not required. Therefore, the aggregate risk is the sum from chronic 

food and water. The chronic aggregate risk assessment has shown that there is no concern. 

Therefore, it is concluded with reasonable certainty that no harm will occur from short-term 

aggregate exposure of sethoxydim.

2. Non-dietary exposure. Sethoxydim is only used for spot treatment in gardens, 

flower beds, recreational areas, and around building and structures. The EPA has determined 

that for sethoxydim, the quantification of dermal exposure risk assessment is not required 

because of lack of dermal and prenatal toxicity in rabbits, and the low dermal absorption of 

sethoxydim. The EPA has also stated that the residential post-application exposure from spot 

treatment is negligible. Therefore based on the lack of dermal toxicity and negligible exposure 

potential, a non-dietary exposure assessment was not conducted.

D. Cumulative Effects

The EPA is currently developing methodology to perform cumulative risk 

assessments. At this time, there is no available data to determine whether sethoxydim has a 

common mechanism of toxicity with other substances or how to include this pesticide in a 

cumulative risk assessment. Unlike other pesticides for which EPA has followed a cumulative 

risk approach based on a common mechanism of toxicity, sethoxydim does not appear to 

produce a toxic metabolite common to other substances.

E. Safety Determination
1. U.S. population. Based on this risk assessment, BASF concludes that there is a 

reasonable certainty that no harm will result to the general population from the aggregate 

exposure to sethoxydim residues.

2. Infants and children. Based on this risk assessment, BASF concludes that there 

is a reasonable certainty that no harm will result to infants or children from the aggregate 

exposure to sethoxydim residues.

F. International Tolerances

There are no CODEX maximum residue levels established or proposed for 

residues of sethoxydim.