Page 2 of 21

In support of the request, Landis submitted the following information/data: MRID 471798-01,-02,-

03,-04,-05,-06,-07 and -08. The Agency has considered the information provided and has 

conducted a search of the open literature to identify additional relevant information. 

Acetone is currently permitted for use as an inert ingredient in pesticide formulations applied pre 

and post harvest under 40 CFR 180.910. It is used as a solvent/co-solvent in a variety of pesticide 

products, including outdoor yard, garden, and turf products, and agricultural crop products. 

Acetone occurs or is found in a variety of foods and consumer products. It is primarily used in the 

manufacture of other chemicals, and secondarily in the manufacture of a variety of consumer 

products. Acetone has been approved by FDA as a secondary direct food additive (Title 21 Code 

of Federal Regulations § 173.210).

The toxicity data base for acetone includes data relative to acetone per se as well as to isopropanol. 

Since isopropanol readily metabolizes to acetone in the body, the Agency has concluded that the 

data regarding isopropanol may be used in conjunction with the data regarding acetone to 

characterize the toxicity of acetone for this assessment. The toxicity studies on isopropanol that are 

used to bridge data gaps for acetone are summarized in this document. 

Acetone has low acute toxicity. It is not a skin irritant or sensitizer but is a defatting agent to the 

skin. Acetone is an eye irritant. The effects of a single exposure to acetone vapor in animals are 

generally similar to the signs of central nervous system (CNS) depression seen in cases of human 

intoxication. 

The toxicity of acetone was evaluated in several subchronic toxicity studies in mice and rats via 

drinking water, gavage and inhalation. The most notable findings in subchronic studies were 

increased liver and kidney weights, and decreased spleen weights. In mice administered acetone 

via drinking water, adverse effects (liver and kidney toxicity) were observed at doses ≥ 1,600 

mg/kg/day. Rats treated with acetone via gavage for 90 days exhibited decreased body weight 

and increased relative kidney and liver weights, hemosiderosis of the spleen and an increased 

incidence and severity of nephropathy at 1,700 mg/kg/day. The NOAEL in rats was 900 

mg/kg/day. In a subchronic toxicity study in rats via gavage, acetone resulted in kidney weight 

changes and lesions at 500 mg/kg/day. The NOAEL in this study was 100 mg/kg/day. Male 

Sprague-Dawley rats were exposed to acetone via inhalation at a concentration of 19,000 ppm 

(45,106 mg/m3) for 3 hours/day, 5 days/week, for 8 weeks. Groups were sacrificed after 2, 4, and 

8 weeks and 2 weeks post-exposure. No treatment related effects were observed in this study at 

exposure concentrations of 19,000 ppm (equal to 11,703mg/kg/day). No dermal toxicity studies 

were available.

Acetone was evaluated in a reproduction screening test with mice via gavage at doses of 0 or 3,500 

mg/kg bw/day (EHRT, 1987). Toxicity was manifested as decreased reproductive index, increased 

gestation length, reduced birth weights, decreased neonatal survival and increased neonatal weight 

gain at 3,500 mg/kg/day. In a 2-generation reproduction study conducted in rats with isopropanol, 

the maternal NOAEL was 500 mg/kg/day and was based on increased in liver and kidney weights 

(absolute and relative) seen at the LOAEL of 1,000 mg/kg/day. The offspring toxicity NOAEL 
Page 3 of 21

was 500 mg/kg/day based on reduced pup body weights and a slight increase in pup mortality seen 

at the LOAEL of 1,000 mg/kg/day. No reproductive parameters were altered at doses up to 1,000 

mg/kg/day. Two developmental toxicity studies in rodents via the inhalation route of exposure 

were also available for review. In mice, maternal (increased incidence of late resorptions) and 

fetal (reduced weight) toxicities were observed at the same dose, 6,600 ppm (approximately 4,066

mg/kg/day). No teratogenic effects were observed in mice. The NOAEL was 2,200 ppm 

(equivalent to 1,348 mg/kg/day). In rats, maternal (reduction in body weight, uterine weight and 

extra-gestational weight gain) and fetal (malformations) toxicities were observed at the same dose, 

11,000 ppm (approximately 6,773 mg/kg/day). The NOAEL was 2,200 ppm (equivalent to 1,348

mg/kg/day). In a developmental toxicity study in rats via gavage with isopropanol, the NOAELs 

for maternal and developmental toxicities were 400 mg/kg/day based on slightly increased 

mortality at 800 mg/kg/day and reduced gestational body weight and reduced gravid uterine 

weights at 1,200 mg/kg/day. Reduced fetal body weights were observed at 800 and 1,200 

mg/kg/day. There was also a developmental toxicity study in rabbits treated with isopropanol via 

gavage. Maternal toxicity was manifested as reduced body weight and food consumption at 480 

mg/kg/day. The NOAEL was 240 mg/kg/day. There were no treatment related effects observed in 

fetuses up to the highest dose tested (480 mg/kg/day). In a developmental neurotoxicity study in 

rats with isopropanol, no developmental neurotoxicity was observed at doses up to 1,200 

mg/kg/day.

Subchronic neurotoxicity studies were available in rats administered acetone via the inhalation or 

dietary routes of exposure. Repeated daily exposures up to 14,240 mg/m3 of acetone produced an 

inhibition of avoidance behavior but did not produce any signs of motor imbalance. Following 

acetone administered via inhalation, rats exhibited transient ataxia at > 28,480 ppm (approximately 

17,544 mg/kg/day).. When acetone was administered in the diet for 14 weeks, neurotoxicity was 

not observed at concentrations up to 1.0 % (approximately 5,000 mg/kg/day). 

Information on the carcinogenicity of acetone is available from dermal studies performed with

acetone used as a vehicle. An increased incidence of tumor formation was not observed up to 0.2 

ml of acetone in mice. Carcinogenicity studies in rodents administered isopropanol via inhalation, 

did not exhibit an increased incidence of tumor formation up to 5,000 ppm (approximately 3,086

mg/kg/day).

Acetone is normally eliminated mainly by enzymatic metabolism (70-80% of the total body 

burden) or excreted via urine or exhaled following inhalation exposure (human volunteer study). 

The first step includes the oxidation to acetol by acetone monooxygenase, associated with 

cytochrome P450IIE1. This step is followed by two different pathways that both lead to the 

formation of pyruvate which –as a key product of intermediary metabolism- can enter various 

pathways, e.g. gluconeogenesis or the citric acid cycle. Acetone is excreted mainly via the lung 

both unchanged and, following metabolism, as carbon dioxide. 

Acetone is currently permitted for use as an inert ingredient in pesticide formulations 

applied pre and post harvest under 40 CFR 180.910. Acetone occurs or is found in a variety of 

foods and consumer products. Acetone has been approved by FDA as a secondary direct food 

additive (Title 21 Code of Federal Regulations § 173.210). The available toxicity studies indicate 

that acetone has very low toxicity. The NOAELs were 900 mg/kg/day and above except one 90-
Page 4 of 21

day toxicity study in rats via gavage in which the NOAEL of 100 mg/kg/day was based on kidney 

toxicity seen at the LOAEL of 500 mg/kg/day. Differences in the observed effect level between 

the drinking water/dietary study and the gavage study may relate to the metabolism of acetone. 

EPA’s Integrated Risk Information System (IRIS) concluded that the drinking water route is 

considered to more closely mimic potential long-term human exposure scenarios. For this reason, 

EPA concluded that the results of gavage study in the case of acetone may not be appropriate for 

the long term risk assessments. As indicated above, the lowest NOAEL identified in the database 

is 900 mg/kg bw/day. For all practical purposes, that is the Agency’s identified limit dose. For 

materials that show no signs of toxicity at or above the limit dose, quantitative risk assessment is 

not necessary. Since no endpoint of concern was identified for the acute and chronic dietary 

exposure assessment and short and intermediate dermal and inhalation exposure, a quantitative risk 

assessment for acetone is not necessary.

Taking into consideration the available information on acetone, there is a reasonable certainty that 

no harm to any population subgroup will result from aggregate exposure when considering dietary 

exposure (including crops, meats and fish) and all other non-occupational sources of pesticide 

exposure for which there is reliable information. Therefore, it is recommended that an exemption 

from the requirements of a tolerance be granted for acetone when used as an inert ingredient in 

pesticide products applied to animals raised for food under 40 CFR § 180.930 and it may be 

considered as safe under § 408(q) of the FFDCA. 

BACKGROUND

The firm Landis International (3185 Madison Highway, PO Box 5126, Valdosta, GA 31601) on 

behalf of Whitmire Micro-Gen (now affiliated with BASF Corp.; 3568 Tree Court Industrial Blvd., 

St. Louis, MO 63122) has submitted a petition (PP#7E7239) which proposed to establish an 

exemption from the requirement of a tolerance. The petition regards the proposed use of acetone, 

as an inert ingredient which serves as a solvent or co-solvent in pesticide formulations. 

The EPA (the Agency) published a Notice of Filing for PP#7E7239 in the Federal Register on 6 

February 2008 (73 FR 6964). No comments were received in response to this Notice.

In 2005, the Agency evaluated acetone (CASRN 67-64-1) as part of the reassessment of tolerance 

exemption for residues of acetone under 40 CFR §180.910, as required under the Food Quality 

Protection Act (FQPA) §408. The reassessment may be found at 

http://www.epa.gov.opprd001/inerts/decisiondoca2k.html. In the 2005 reassessment, the Agency 

concluded that the tolerance exemption for acetone under 40 CFR §180.910 was found to be safe 

under the safety standards described in FFDCA §408.

Pesticide Uses: Acetone is permitted for use as an inert ingredient in pesticide formulations applied 

pre and post harvest under 40 CFR §180.910. It is used as a solvent/co-solvent in a variety of 

pesticide products, including outdoor yard, garden, and turf products, and agricultural crop 

products. 

Other Uses: Acetone is in a variety of foods and consumer products. It is primarily used in the 

manufacture of other chemicals, and secondarily in the manufacture of a variety of consumer 
Page 5 of 21

products (e.g., paints, varnishes, automotive care products, and personal care products). In 

addition, acetone has been approved by FDA as a secondary direct food additive (see 21 CFR 

§173.210 for more information). 

PHYSICAL/CHEMICAL PROPERTIES OF ACETONE (Mallinckrodt 2009)

Structural Formula www.chem.purdue.edu/gchelp/molecules/acetoneb.html

Chemical Formula 

(CH3)CO2

Molecular weight

58.08

Appearance:

Clear, colorless, volatile liquid. 

Odor:

Fragrant, mint-like 

Solubility:

Miscible in all proportions in water. 

Specific Gravity:

0.79 @ 20oC/4oC 

pH:

No information found. 

% Volatiles by volume @ 21oC (70oF):

100 

Boiling Point:

56.5oC (133oF) @ 760 mm Hg 

Melting Point:

-95oC (-139oF) 

Vapor Density (Air=1):

2.0 

Vapor Pressure (mm Hg):

400 @ 39.5oC (104oF) 

Evaporation Rate (BuAc=1):

ca. 7.7 
Page 6 of 21

HUMAN HEALTH RISK ASSESSMENT

The toxicity data base for acetone includes data regarding acetone as well as isopropanol. Since

isopropanol readily metabolizes to acetone in the body, the Agency has concluded that the data on 

isopropanol can be used in conjunction with the data on acetone to characterize the toxicity of 

acetone for this assessment. The toxicity studies on isopropanol that are used to bridge the data 

gaps for acetone are discussed in this document. 

The toxicity of acetone has been extensively studied. A summary of the toxicity of acetone is 

presented in this document. This assessment is based on information and data submitted by the 

petitioner, as well as, information and data found in the public literature including various peer 

reviewed articles and documents such as EPA’s 2005 Reassessment Document on Acetone for the 

Tolerance Exemption Under 40 CFR 180.910 (EPA, 2005); EPA’s Integrated Risk Information 

System (IRIS; 2003); the National Toxicology Program 1991 Toxicity Studies of Acetone in 

F344/N Rats and B6C3F1 Mice in Drinking Water Studies (NTP, 1991); the U.S. Agency for 

Toxic Substances and Disease Registry (ATSDR; 1994); U.S. EPA SIDS Initial Assessment 

Report (SIAR) for the 9th SIAM on acetone (SIAR, 1999); the International Program on Chemical 

Safety (IPCS), INCHEM document on acetone, (INCHEM, 1998); as well as, the Hazardous 

Substance Database (HSDB, 2009). 

Acute Toxicity

Acetone has low acute toxicity. It is not a skin irritant or sensitizer but is a defatting agent to the 

skin. Acetone is an eye irritant. The effects of a single exposure to acetone vapor in animals are 

generally similar to the signs of central nervous system (CNS) depression seen in cases of human 

intoxication. Vapor concentrations in excess of 24,000 mg/m3 (24 mg/L) are generally required to 

elicit any sign of acute acetone intoxication in animals. (EPA, 2005). 

Summary of Acute Toxicity Data for Acetone

Parameter Toxicity Value Reference

Acute Oral toxicity

Rat LD50: 8400 mg/kg 

Mouse LD50: 5250 mg/kg

Rabbit LD50: 5300 mg/kg

(SIAR, 1999)

Acute Dermal Toxicity Rabbit LD50: >15,700 mg/kg

Acute Inhalation 

Toxicity Rat LC50: 50,000 mg/m3

Eye Irritation, rabbit Draize

Highly irritating

Skin Irritation, rabbit Not irritating

Acetone

Subchronic Toxicity Oral

Groups of five male and five female F344/N rats were administered acetone in drinking water at 

concentrations of 0, 5,000, 10,000, 20,000, 50,000, or 100,000 ppm for 14 days. Time- weighted 
Page 7 of 21

average doses for males were 0, 700, 1,600, 2,600, 4,300, and 6,900 mg/kg/day, respectively, and 

for females 0, 750, 1,500, 2,300, 4,350, and 8,600 mg/kg/day, respectively. All animals survived 

to termination. Water consumption was reduced in both sexes at 50,000 and 100,000 ppm. Final 

body weights of males given 50,000 and 100,000 ppm were 87 and 63%, respectively, of controls, 

and final body weights of females given 100,000 ppm was 87% of controls. Increases in relative 

liver and kidney weights were observed in both sexes at ≥20,000 ppm, relative testes weights were 

increased at ≥50,000 ppm, and thymus weights were decreased in animals in the 20,000 and 

50,000 ppm dosed groups. Bone marrow hypoplasia was noted in all high-dose males, but in none 

of the controls. The LOAEL was 2,600 mg/kg/day based on increased relative liver and kidney 

weights, and decreased thymus weights. The NOAELwas 1,500 mg/kg/day (NTP, 1991 as cited in 

IRIS, 2003).

Groups of 10 male and 10 female F344/N rats were administered acetone in drinking water at 

concentrations of 0, 500, 5,000, 10,000, 20,000, or 50,000 ppm for 13 weeks. Time-weighted 

average doses for males were 0, 200, 400, 900, 1,700, and 3,400 mg/kg/day respectively, and for 

females 0, 300, 600, 1,200, 1,600, and 3,100 mg/kg/day, respectively. In rats, signs of possible 

toxic effects occurred mainly at 20,000 and 50,000 ppm. The toxic effects at 20,000 ppm included 

decreases in body weight and increase in relative organ weights (kidney and liver), mild 

macrocytic anemia (decreases in hemoglobin, erythrocytes, reticulocytes, and platelets, and 

increases in mean corpuscular hemoglobin, mean cell volume, leukocytes, and lymphocytes), 

hemosiderosis of the spleen, and an increased incidence and severity of nephropathy. The 

hematological changes observed in this study were statistically significant but not considered to be 

biologically relevant because the changes in the parameters were small in magnitude and may 

represent normal individual variability. At 50,000 ppm effects in the testes were also observed

(including decreases in caudal and right epididymal weight and sperm motility and an increase in 

abnormal sperm). Male rats appeared to be the most sensitive species with the kidney and liver 

identified as target organs, with a LOAEL of 1,700 mg/kg/day (20,000 ppm) and a NOAEL of 900 

mg/kg/day (10,000 ppm). (NTP, 1991 as cited in IRIS, 2003)

Groups of 30 male and female Sprague-Dawley rats were administered acetone by oral gavage at 

doses of 0, 100, 500, and 2,500 mg/kg/day for 90 days. The critical effect noted was kidney 

pathology. The LOAEL for this study is 500 mg/kg/day based on organ weight changes and kidney 

lesions and the NOAEL is 100 mg/kg/day. Differences in the observed effect level between the 

above drinking water study and this gavage study may relate to the method of administration. In 

gavage or bolus experiments, more acetone appears to be shunted to the kidney, producing higher 

concentrations in the urine and higher rates of metabolism through the propanediol pathway 

compared with the more gradual administration through drinking water. This could account for 

differences in the nephropathy severity levels observed with drinking water compared with gavage 

administration. The drinking water route is considered to more closely mimic potential long-term 

human exposure scenarios. (IRIS, 2003)

Male Sprague-Dawley rats were exposed to acetone via inhalation at a concentration of 19,000 

ppm (45,106 mg/m3

) for 3 hours/day, 5 days/week, for 8 weeks. Groups were sacrificed after 2, 4, 

and 8 weeks and 2 weeks post-exposure. Clinical chemistry indices (i.e., SGOT, LDH, BUN, liver 

Rats-Inhalation Toxicity
Page 8 of 21

triglyceride content, lung fluid content) and histopathological examination of tissues (i.e., lung, 

liver, brain, kidney, and heart) failed to reveal manifestations of acute injury or residual organ 

damage at any sacrifice time. There was slight decrease in body weight gain, however, the 

differences between treated and control groups were not considered to be statistically significant. 

The NOAC is considered to be 19,000 ppm (approximately 11,704 mg/kg/day). (Bruckner and 

Peterson, 1981)

Rats-Inhalation Developmental and Reproductive Toxicity

In an inhalation developmental toxicity study, Sprague-Dawley Rats were exposed to 0, 440, 

2,200, and 11,000 ppm (0, 1,045, 5,200, or 26,100 mg/m3) acetone for 6 hrs/day on gestation days 

6-19. There were no maternal deaths. Pregnant females in the 11,000 ppm group exhibited a 

significant reduction in body weight, uterine weight and extra-gestational weight gain (maternal 

body weight at sacrifice minus gravid uterine weight minus day 0 maternal body weight). No 

other symptoms of maternal toxicity were evident. The incidence of fetal malformations was not 

significantly increased in the acetone exposed groups compared to controls. However the percent 

of litters with at least one pup with malformations was greater at 11,000 ppm than for control (11.5 

vs 3.8%). None of the major malformations observed at 11,000 ppm (cleft sternum, ectopic heart, 

major vessel malformations, edema, unilateral arhinia, and microstomia, vertebral agenesis, or a 

missing tail) were observed in control litters. Several fetuses at 11,000 ppm had multiple 

malformations. It was concluded that the 2,200 ppm (approximately 1,355 mg/kg/day) acetone 

level was the no observed effect level (NOAEL) in the Sprague Dawley rat for developmental 

toxicity. The developmental LOAELwas 11,000 ppm (approximately 11,000 mg/kg/day) based on 

major malformations. The LOAEL for maternal toxicity was 11,000 ppm (approximately 6,766

mg/kg/day) based on reduced body weight, uterine weight and extra-gestational weight gain. 

(NTP, 1988 as cited in SIAR, 1999)

Rats- Oral Neurotoxicity

In a neurotoxicity assessment study with acetone, young rats were fed aqueous solutions 

containing 0.5 and 1% (approximately 5,000 mg/kg/day) acetone for 14 weeks. The study 

demonstrated that there were no pathological findings in the nervous system of rats exposed to 

acetone. (Spencer et al.,1978).

Rats-Inhalation Neurotoxicity

Mild neurobehavioral changes have been observed in rats repeatedly exposed to high vapor 

concentrations of acetone. Female rats exposed 4 hr/day for 2 weeks to acetone concentrations of 

7,120, 14,240, 28,480, and 37,975 mg/m3 were examined for their response to avoidance and 

escape stimuli before and after each exposure (Goldberg et al., 1964). Repeated daily exposures to 

14,240 mg/m3 of acetone produced an inhibition of avoidance behavior but did not produce any 

signs of motor imbalance. Acetone concentrations of 28,480 and 37,975 mg/m3 produced ataxia in

several animals after a single exposure, however, a rapid tolerance developed and ataxia was not 

seen on subsequent days. In a recent schedule controlled operant performance study, acetone did 

not cause any permanent effects in rats exposed to the vapor for 13 weeks at 2,375, 4,750, and 
Page 9 of 21

9,495 mg/m3. The LOAEL was not established. The NOAEL was 9,495 mg/m3 (approximately

2,713 mg/kg/day) (Christoph and Stadler, 1997 as cited in SAIR, 1999).

Groups of adult male rats (10/group) were used to assess whether subchronic inhalation exposure 

to 0, 1,000, 2,000, or 4,000 ppm of acetone vapor altered schedule-controlled operant performance. 

Rats were exposed to acetone vapor for 6 hr/day, 5 d/wk, for a 13-wk period. Extensive training 

prior to the exposure series established a stable baseline of lever-pressing on a multiple fixed-ratiofixed-interval (FR 20-FI 120 s) schedule of food presentation. Operant sessions occurred prior to 

each daily exposure to avoid confounding the detection of enduring behavioral effects with 

transient acute effects. FI response rate, FI index of curvature, and FR running rate of response 

were not affected during or after the 13-wk exposure series. FR post-reinforcement pause duration 

for the control group increased during the course of the study more than that of the 2,000 ppm and 

4,000 ppm groups, which changed only slightly relative to pretreatment baseline. Based on the 

performance of historical controls that had FR pause durations similar to those of acetone-treated 

groups, the differences of FR pause duration were probably due to drift of the concurrent control 

group and were not related to acetone treatment. Prolonged exposure to up to 4,000 ppm acetone 

vapor does not appear to have enduring effects on nervous system functions that mediate the 

performance of a complex, learned task.” The LOAEL was not established. The NOAEL was 

4,000 ppm (approximately 2,464 mg/kg/day; Christoph et al., 2003).

Mice-Oral Subchronic Toxicity

Groups of five male and five female B6C3F1 mice were administered acetone in drinking water at 

concentrations of 0, 5,000, 10,000, 20,000, 50,000, or 100,000 ppm for 14 days. Time-weighted 

average doses for males were 0, 960, 1,600, 3,900, 6,300, and 10,000 mg/kg/day respectively, and 

for females 0, 1,600, 3,000, 5,500, 8,800, and 13,000 mg/kg/day respectively. Kidney weights 

were increased at ≥ 50,000 ppm in males and females, and liver weights were increased at ≥ 5,000 

ppm in males and ≥ 20,000 ppm in females. The effect on the liver weight up to 10,000 ppm in 

males and 20,000 ppm in females was considered to be an adaptive response rather than an adverse 

effect since no histopathology was reported at that dose level. Dose-related increases in the 

incidence and severity of centrilobular hepatocellular hypertrophy were observed in males at ≥

20,000 ppm and in females at ≥ 50,000 ppm. The NOAEL is considered to be 1,600 mg/kg/day in 

males based on liver toxicity at 3,900 mg/kg/day. The NOAEL is considered to be 5,500 

mg/kg/day in females based on liver toxicity at the LOAEL of 8,800 mg/kg/day (NTP, 1991).

Groups of 10 male and 10 female B6C3F1 mice were administered acetone in drinking water at 

concentrations of 0, 1,250 (male only), 2,500, 5,000, 10,000, 20,000, or 50,000 (females only) ppm 

for 13 weeks. Time-weighted average doses for males were 0, 380, 600, 1,400, 2,300, and 4,900 

mg/kg/day, respectively, and for females 0, 900, 2,000, 4,200, 5,900, and 11,000 mg/kg/day, 

respectively. No deaths occurred and no clinical signs of toxicity were observed in any group. The 

only significant effects seen were increases in absolute and relative liver weights and a minimal 

degree of centrilobular hepatocellular hypertrophy in two of five females receiving drinking water 

with 50,000 ppm acetone (equivalent to 11,298 mg/kg/day). Mild hepatic changes were observed 

in males at 20,000 ppm or higher doses for 14 days in a preliminary range-finding study, but these 

changes did not persist after 13 weeks, suggesting the development of tolerance to acetone. The 

liver was identified as the target organ in male and female mice. The LOAELs for males and 
Page 10 of 21

females were 4,900 and 11,000 mg/kg/day respectively, and the NOAELs were 2,300 and 5,900 

mg/kg/day respectively. The NOAEL and LOAEL for male mice were based on transient effects 

observed in the 14 day study (NTP, 1991).

Mice-Oral Developmental Toxicity 

“Environmental Health Research Testing (EHRT; 1987) evaluated acetone in a reproduction 

screening test using mice. Acetone in distilled water was administered by gavage to groups of 50 

mated CD-1 mice on days 6-15 of gestation at doses of 0 or 3,500 mg/kg per day. Parameters of 

toxicity evaluated included maternal toxicity (mortality, body weight and clinical signs), number 

of live and dead offspring, pup body weight at birth, survival and litter weight at postpartum day 3. 

Although two treated dams exhibited clinical signs and eventually died, the authors did not 

consider that maternal mortality had been increased by treatment with acetone. Survivors 

exhibited no clinical signs or effects on body weight. Effects attributed to acetone included 

decreased reproductive index, increased gestation length, reduced birth weights, decreased 

neonatal survival and increased neonatal weight gain.” (EHRT, 1987 as cited in INCHEM, 1998).

The LOAEL for developmental effects in mice is 3,500 mg/kg/day. The NOAEL was not 

established in this study. (ATSDR, 1994). 

Mice-Inhalation Developmental and Reproductive Toxicity

In an inhalation developmental toxicity study, mice were exposed to 0, 440, 2,200, and 6,600 ppm 

(0, 1,045, 5,200, or 15,670 mg/m3) acetone for 6 hrs/day on gestation days 6-17. Exposure to 

6,600 ppm acetone resulted in a statistically significant reduction in fetal weight and a slight but 

statistically significant increase in the percent incidence of late resorptions. The incidence of 

malformations was not increased at any exposure level. It was concluded that the 2,200 ppm 

acetone level was the no observed effect level in the Swiss (CD-1) mouse for developmental 

toxicity. The developmental LOAEL was 6,600 ppm based on reduced fetal weight. The maternal 

LOAEL was 6,600 ppm based on an increase in the percent incidence of late resorptions. The 

NOAEL for maternal toxicity was also 2,200 ppm. Acetone did not produce any teratogenic 

effects at any of the exposure concentrations tested. (NTP, 1988; as cited in SIAR, 1999).

Rodents- Dermal Carcinogenicity/Chronic Toxicity

“Information on the carcinogenicity of acetone is available from dermal studies performed with

mice. In each of these studies, acetone was used as the vehicle to evaluate the effects of a test 

chemical. The test design therefore included untreated and vehicle-treated study groups. The 

carcinogenicity of acetone was evaluated in a group of 29 female ICR/Ha Swiss mice treated 

topically with 0.1 mL of acetone or 0.1 mL of acetone-water mixture (9:1) three times per week 

for up to 424 days (Van Duuren et al., 1978). Histopathological analysis of all major organs 

revealed a total of 14 lung tumors, one liver tumor, one forestomach tumor, and no skin tumors in 

the acetone and acetone/water treatment groups. Lung papillary tumors were seen in 37% of the 

untreated mice and 24% of the acetone or acetone-water treated mice. The incidence of 

forestomach tumors in acetone or acetone-water treated mice was comparable to untreated mice. 

Except for one undifferentiated malignant liver tumor, which was not cited as a remarkable 

finding, the incidence of systemic tumors in the acetone and acetone-water treated mice was not 
Page 11 of 21

different from the background incidence in untreated mice. In another study, the application of 0.2 

mL of acetone to the shaved dorsal skin of male and female CF1 mice once per week for two years 

had no effect on the survival of the 300 animals tested (Zakova et al., 1985). Dermal inflammatory 

reactions (focal acanthosis, dermal fibrosis) were seen in 6% of the animals and a fibrosarcoma 

was seen in one male mouse. An historical analysis of the organ pathology observed in two 

previous dermal carcinogenicity studies showed no evidence of a treatment-related increase in 

tumors or organ lesions from acetone (Ward et al., 1986). Sixty female SENCAR mice received 

0.2 mL of acetone once or twice per week for up to 92 weeks (dermal route of exposure). The 

major organs and tissues from all of the animals were examined both macroscopically and 

microscopically following necropsy. Fifty percent of the animals survived past 96 weeks of age 

with 15 of the mice dying due to neoplastic lesions and 27 due to non-neoplastic lesions.” (SIAR, 

1999).

The Agency (EPA, 2005) noted the IRIS (2003) conclusion that the cancer data on acetone are 

inadequate because of limited testing in long-term cancer bioassays. Nevertheless, IRIS states that 

“Acetone has a long history of industrial use as a solvent. To date there are no epidemiological 

studies demonstrating an association between exposure to acetone and increased risk of cancer”. 

Both IRIS and the SIAR reported that genetic toxicology studies, which used acetone as the test 

material rather than the solvent, have been uniformly negative. The SIAR concluded that acetone 

is not carcinogenic via the dermal route of exposure. 

Mutagenicity

“Acetone has been repeatedly tested in a variety of prokaryotic and eukaryotic test systems without 

causing genotoxic effects. Studies in the Salmonella assay have shown acetone to be nonmutagenic. Acetone was not geno-toxic to Schizosaccharomyces pombe either with or without 

metabolic activation. Acetone did not produce genotoxic effects in an embryo cell transformation 

assay performed in rats and mice, and was also negative in a micronucleus assay using hamsters. 

Acetone did not cause chromosomal aberrations or sister chromatid exchanges in Chinese hamster 

ovary cells treated at concentrations up to 5 mg/mL. Acetone concentrations ranging from 10.5 to 

20.9 mM (0.6 to 1.2 mg/mL) also did not cause chromosomal aberrations or sister chromatid 

exchanges in cultured human lymphocytes. Acetone did not cause point mutations at the 

thymidine kinase locus in L5178Y mouse lymphoma cells treated at a level of 10 mg/mL.” 

(SIAR, 1999).

Mice-Oral Immunotoxicity

A study was conducted “to investigate the immunotoxicity potential of acetone in mice following a 

more direct systemic route of dosing via drinking water for 28 days. CD-1 male mice consumed 

average daily acetone doses of 121, 621, or 1,144 mg/kg/day. The antibody, plaque-forming cell 

(AFC) assay was performed to measure the T cell-dependent, anti-sheep red blood cell 

immunoglobulin M (IgM) response, and hematology and thymus weights were evaluated to 

provide additional insight into the potential effects to the immune system. Body weights, white 

blood cell (WBC), numbers, red blood cell (RBC) counts, and hemoglobin and hematocrit levels 

showed no treatment-related effects at any dose of acetone. Eosinophil percentages were variable 

but also showed no dose-related trends. Spleen and thymus weights were not statistically different 
Page 12 of 21

from controls and there were no effects on spleen cellularity or AFC response as a result of 

acetone administration. The AFC responses ranged from 1,088 to 1,401 AFCs/10+6 splenocytes 

and were not statistically different from controls (1,277 AFCs/10+6 cells). Mice treated with 

cyclophosphamide (20 mg/kg) on days 25 to 28 demonstrated a 94% reduction in AFC/10+6 cells. 

Thus, the direct systemic administration of acetone did not produce evidence for immunotoxicity 

in CD-1 mice and the no observed adverse effect level (NOAEL) in this study was determined to 

be 1,144 mg/kg/day”;the highest dose tested. (Woolhiser et al., 2006).

Rats-Metabolism and Pharmacokinetics

“Acetone is normally eliminated mainly by enzymatic metabolism (70-80% of the total body 

burden) or excreted via urine or exhaled following inhalation exposure (human volunteer study) . 

The metabolic pathways of acetone seem to be similar in humans and laboratory animals. The 

primary site of metabolism of acetone is the liver. The first step includes the oxidation to acetol by 

acetone monooxygenase, associated with cytochrome P450IIE1. This step is followed by two 

different pathways that both lead to the formation of pyruvate which –as a key product of 

intermediary metabolism- can enter various pathways, e.g. gluconeogenesis or the citric acid cycle. 

Acetone is excreted mainly via the lung both unchanged and, following metabolism, as carbon 

dioxide. The fraction of unchanged acetone found in expired breath increases with elevated 

exposure concentrations due to the saturation of metabolic pathways. ... At higher blood levels the 

metabolic elimination approaches zero order kinetics and the respiratory tract is the main route of 

elimination via exhalation of unchanged acetone. Excretion via urine is only a minor route of 

elimination” (AEGL, 2005).

Isopropanol

Rats-Oral Developmental and Reproductive Toxicity

A two-generation reproduction toxicity study was conducted in rats with isopropanol. Thirty rats 

of each sex per group (P1) were dosed once daily by oral gavage with 0, 100, 500, or 1,000 

mg/kg/day for 10 weeks prior to mating and throughout the mating period for the F1(P2) animals 

and until the day prior to euthanasia. F1(P2) animals were dosed daily for 10 weeks prior to 

mating and throughout the mating period for F2 animals and until the day prior to euthanasia. 

F1(P2) litters were dosed beginning on day 21 postpartum. P1 and P2 females were dosed during 

gestation, lactation, and through weaning on Day 21 postpartum of the F1 and F2 litters. It was 

concluded that a dose of 1000 mg/kg/day of isopropanol produced evidence of parental effects as 

indicated by increases in absolute and/or relative liver and/or kidney weights compared to controls. 

In addition, increased absolute or relative liver weights were observed in parental animals dosed at 

500 mg/kg/day. These effects were not considered to be an adverse effect. Centrilobular 

hepatocyte hypertrophy was observed in a few high dose P2 male rats. Increased mortality was 

observed in high dose F1 offspring compared to controls. In addition high dose offspring of both 

generations were lighter than controls at several intervals. Therefore the parental NOAEL was 

established at 500 mg/kg/day. The parental LOAEL was 1,000 mg/kg/day based on increased 

absolute and/or relative liver and/or kidney weights. The reproductive NOAEL was 1000 

mg/kg/day; the LOAEL was not established. The offspring toxicity NOAEL was 500 mg/kg/day 
Page 13 of 21

based on reduced offspring body weights and increased mortality observed at 1,000 mg/kg/day. 

(Bevan, 1995; as cited in VCCEP, 2003).

In a developmental toxicity study, timed-pregnant CD (Sprague-Dawley) rats, 25/group, were 

dosed orally by gavage with aqueous isopropanol (IPA) solutions at 0, 400, 800, or 1,200 

mg/kg/day, once daily on Gestational Days (GD) 6 through 15 at a dosing volume of 5 ml/kg. The 

pregnancy rate was high and equivalent across all groups; no dams aborted, delivered early, or 

were removed from the study. In rats, two dams (8%) died at 1,200 mg/kg/day and one dam (4%) 

died at 800 mg/kg/day. Maternal body weights and weight gain were equivalent across all groups, 

except for statistically significantly reduced gestational weight gain (GD- 20; 89.9% of control 

value), associated with statistically significantly reduced gravid uterine weight at 1200 mg/kg/day

(89.2% of control value). There were no treatment-related clinical signs or effects on maternal 

food consumption. All gestational parameters evaluated were equivalent across groups, including 

pre-and post-implantation loss, fetal sex ratios, and litter size. Twenty-two to 25 litters were 

examined per group. Fetal body weights per litter were statistically significantly reduced at the 

two highest doses (97.3 (n.s.), 94.7, and 94.3% of controls at 800 mg/kg/day and 92.1, 91.9, and 

95.4% of controls at 1200 mg/kg/day for all fetuses and males and females separately). No 

evidence of increased teratogenicity was observed at any dose tested in rats. Therefore, IPA was 

not teratogenic to CD rats. The NOAELS for both maternal and developmental toxicity were 400 

mg/kg/day in rats. The maternal NOAEL was 800 mg/kg/day; the LOAEL was 1,200 mg/kg/day 

based on reduced gestational weight gain and gravid uterine weight). The developmental NOAEL 

was 400; the LOAEL was 800 mg/kg/day based on reduced fetal body weights per litter. (Tyl 

R.W. et al; 1994).

Rabbits

In a developmental toxicity study, artificially inseminated New Zealand white rabbits, 15/group, 

were dosed orally with isopropanol (IPA) at 0, 120, 240, or 480 mg/kg/day once daily on GD 6 

through 18 at 2 ml/kg. The pregnancy rate was high and equivalent across all groups. No does 

aborted, delivered early, or were removed from the study. Four does (26.7% ) died at 480 

mg/kg/day. Maternal body weights were statistically significantly reduced during treatment (GD 

6-18) at 480 mg/kg/day (45.4% of control value) with a nonsignificant reduction in gestational 

weight change (GD 0-30; 77.3% of control value) at this dose. Profound clinical signs of toxicity 

and statistically significantly reduced maternal food consumption were observed at 480 mg/kg/day. 

All gestational parameters were equivalent across all doses administered. Thirteen to 15 litters 

were evaluated per group except for the 480 mg/kg/day group with 11 litters (due to maternal 

deaths). There were no treatment-related effects on pre- or postimplantation loss, fetal sex ratio, 

litter size, or fetal body weight/litter. Moreover, no evidence was found of increased teratogenicity 

at any dose tested in rabbits. Therefore, IPA was not teratogenic to NZW rabbits. The NOAELS 

for maternal and developmental toxicity were 240 and 480 mg/kg/day, respectively. (Tyl R.W. et 

al; 1994).
Page 14 of 21

Rats-Developmental Neurotoxicity

Isopropanol was administered by gavage to timed-mated rats from Gestation Day (GD) 6 through 

Postnatal Day (PND) 21. Doses administered were 0, 200, 700, or 1,200 mg/kg/day in a volume of 

5 ml/kg. The dams were allowed to deliver and body weights and food consumption were 

recorded during gestation and lactation. Pups were counted, examined, sexed, and weighed on 

PND 0, 4, 7, 13, 17, 21, 36, 49, and 68. Litters were culled to eight pups (4:4 or 5:3 sex ratio) on 

PND 4 and litters without acceptable numbers of male and female pups were eliminated from the 

study. Pups were weaned on PND 22, and two pups from each litter and their dams were killed. 

Six of these pups from each dose group were perfused in situ for histopathological examination of 

the central and peripheral nervous system. Brains of the remaining pups were divided into four 

regions and weighed. Maternal liver and kidney weights were recorded. Weaned pups were 

assessed for day of testes descent or vaginal opening and for motor activity on PNDs 13, 17, 21, 

47, and 58; auditory startle on PNDs 22 and 60; and active avoidance on PNDs 60-64. These pups 

were euthanized and examined on PND 68. One high-dose dam died on PND 15, but there were 

no other clinical observations or effects on maternal weight, food consumption, or gestation length 

suggesting that the death could have been due to gavage error. Pup survival, weight, sex ratio, and 

sexual maturation were unaffected. There were no biologically significant findings in the 

behavioral tests, no changes in organ weight, and no pathological findings that could be attributed 

to isopropanol exposure. In conclusion, there was no evidence of developmental neurotoxicity 

associated with isopropanol exposure as high as 1,200 mg/kg/day. The NOAEL was 1,200 

mg/kg/day. The LOAEL was not established. (Bates et al., 1994).

Rodents- Inhalation Carcinogenicity/Chronic Toxicity

Four groups of animals, each consisting of 75 CD-1 mice/sex and 75 Fischer 344 rats/sex, were 

exposed to isopropanol vapor at target concentrations of 0, 500, 2,500, or 5,000 ppm. Animals 

assigned to the core group (55 mice/sex/group and 65 rats/sex/group) were exposed for 6 hr/day, 5 

consecutive days/week for at least 78 weeks for the mice or 104 weeks for the rats. Ten 

mice/sex/group and 10 rats/sex/group were assigned to an interim euthanasia group and were 

terminated during weeks 54 and 73, respectively. In addition, 10 mice/sex/group were assigned to 

a recovery group and did not receive any further exposure following week 53 but were retained 

until the core group of animals was euthanized. It was concluded that exposure of rats and mice to 

isopropanol vapor produced clinical signs of toxicity (hypoactivity, lack of startle response or 

narcosis) during exposures at 2,500 and 5,000 ppm as well as increased body weight and body 

weight gain. For rats, a number of nonneoplastic lesions were observed, with the most significant 

lesions being in the kidney. The only neoplastic lesion observed for male rats was an increase in 

interstitial cell adenomas of the testis, which was considered to represent marked hyperplasia and

not autonomous growth. In addition the increased incidence of testicular tumors in the isopropanol 

exposed groups appeared to be reflective of the lower incidence observed in the control group. No 

increased frequencies of neoplastic lesions were noted in the female rats exposed to isopropanol. 

There were no increased frequencies of neoplastic lesions noted for male or female mice from any 

isopropanol exposure groups. Thus, for both rats and mice, the no observed effect level (NOEL) 

for toxic effects was 500 ppm and the NOEL for oncogenicity effects was determined to be greater 

than 5,000 ppm. (H. Burleigh-Flayer, 1997; as cited in VCCEP, 2003).
Page 15 of 21

Toxicity Endpoint Selection:

Acetone is currently permitted for use as an inert ingredient in pesticide formulations 

applied pre and post harvest under 40 CFR 180.910. Acetone occurs or is found in a variety of 

foods and consumer products. Acetone has been approved by FDA as a secondary direct food 

additive (Title 21 Code of Federal Regulations § 173.210). The available toxicity studies indicate 

that acetone has very low toxicity. The NOAELs were 900 mg/kg/day and above except one 90-

day toxicity study in rats via gavage in which the NOAEL of 100 mg/kg/day was based on kidney 

toxicity seen at the LOAEL of 500 mg/kg/day. Differences in the observed effect level between 

the drinking water/dietary study and the gavage study may relate to the metabolism of acetone. 

EPA’s Integrated Risk Information System (IRIS) concluded that the drinking water route is 

considered to more closely mimic potential long-term human exposure scenarios. For this reason, 

EPA concluded that the results of gavage study in the case of acetone may not be appropriate for 

the long term risk assessments. As indicated above, the lowest NOAEL identified in the database 

is 900 mg/kg bw/day. For all practical purposes, that is the Agency’s identified limit dose. For 

materials that show no signs of toxicity at or above the limit dose, quantitative risk assessment is 

not necessary. Since no endpoint of concern was identified for the acute and chronic dietary 

exposure assessment and short and intermediate dermal and inhalation exposure, a quantitative risk 

assessment for acetone is not necessary.

SPECIAL CONSIDERATION OF INFANTS AND CHILDREN

Section 408 of the FFDCA provides that EPA shall apply an additional margin of safety for infants 

and children in the case of threshold effects to account for prenatal and post natal toxicity and the 

completeness of the database on toxicity and exposure unless EPA determines that a different 

margin of safety will be safe for infants and children. EPA concludes that the FQPA safety factor 

could be reduced to 1X for acetone for the following reasons.

Given the lack of concern for hazard posed by acetone, EPA concludes that there are no dietary or 

aggregate dietary/non-dietary risks of concern as a result of exposure to acetone in food and water 

or from residential exposure. As discussed in this unit, EPA expects aggregate exposure to acetone 

to pose no appreciable dietary risk given that the data show a lack of systemic toxicity at doses ≥ 

900 mg/kg/day a and a lack of any increased susceptibility of infants and children. Taking into 

consideration of all available information on acetone, EPA concludes that there is a reasonable 

certainty that no harm will result to the general population, or to infants and children from 

aggregate exposure to acetone residues.

• The database is considered adequate for FQPA assessment. Since isopropanol readily 

metabolizes to acetone in the body, the Agency has concluded that the data regarding 

isopropanol may be used in conjunction with the data regarding acetone to characterize the 

toxicity of acetone for this assessment. The following acceptable studies are available for 

FQPA assessment: The available studies with acetone included: developmental toxicity 

study in rats and mice (inhalation), and developmental and reproductive screening test in 

mice (gavage), The available studies with isopropanol included: 2-generation reproduction 

study in rats (gavage), oral developmental toxicity study in rats, oral developmental 

toxicity study in rabbits and oral developmental toxicity study in rats. .
Page 16 of 21

• In the reproduction screening test in mice, toxicity was manifested as decreased 

reproductive index, increased gestation length, reduced birth weights, decreased neonatal

survival and increased neonatal weight gain at 3,500 mg/kg/day; the only dose tested. In 

the developmental toxicity studies via the inhalation route in rodents, fetal toxicity was 

observed only in the presence of maternal toxicity, which occurred at > approximately 

4,477 mg/kg/day and 7,457 mg/kg/day in mice and rats, respectively. There was no 

evidence of increased susceptibility in developmental toxicity studies conducted with 

isopropanol since the developmental effects were observed in the presence of maternal 

toxicity or at a dose above the dose produced maternal toxicity. No evidence of increased 

susceptibility was observed in the 2-generation reproduction study in rats conductedwith 

isopropanol. No developmental neurotoxicity was observed in rats at isopropanol doses up 

to 1,200 mg/kg/day.

• Two neurotoxicity studies (oral and inhalation) were available in rats treated with acetone. 

Neurotoxicity was not observed in either study up to 2,713 and 5,000 mg/kg/day in the 

inhalation and oral studies, respectively. 

• A developmental neurotoxicity study was available for review in rats treated with , 

isopropanol. There was no evidence of developmental neurotoxicity associated with 

ispopropanol exposure as high as 1,200 mg/kg bw/day. 

• An immunotoxicity study was available in mice treated with acetone. Evidence of 

immunotoxicity was not observed up to 1,144 mg/kg/day.

• Residue values used in the dietary risk assessment and exposure values used in the 

residential assessment are unlikely to underestimate risk. The food exposure assessments 

are considered to be highly conservative as they are based on the use of the highest 

tolerance level from the surrogate pesticides for every food and 100% crop treated is 

assumed for all crops. EPA also made conservative (protective) assumptions in the ground 

and surface water modeling used (100 ppb) to assess exposure to acetone in drinking water

Based upon the information available, acetone is not significant as a developmental toxicant. 

Based on overall weight of evidence, the EPA concludes the additional 10X FQPA safety factor 

can be reduced to 1X.

VI. Dietary Exposure Assessment:

Given the lack of concern for hazard posed by acetone, EPA concludes that there are no dietary or 

aggregate dietary/non-dietary risks of concern as a result of exposure to acetone in food and water 

or from residential exposure. As discussed in this unit, EPA expects aggregate exposure to acetone 

to pose no appreciable dietary risk given that the data show a lack of systemic toxicity at doses ≥ 

900 mg/kg/day a and a lack of any increased susceptibility of infants and children. Taking into 

consideration of all available information on acetone, EPA concludes that there is a reasonable 

certainty that no harm will result to the general population, or to infants and children from 

aggregate exposure to acetone residues.
Page 17 of 21

ENVIRONMENTAL FATE CHARACTERIZATION

In the Agency’s 2005 assessment, the Agency stated: Acetone is considered to be very volatile, 

with a vapor pressure of 182 mm Hg at 68o F (20o C). A substantial amount of acetone can be 

found in water, which is consistent with high water solubility and its small, but detectable, 

presence in rain water, sea water, and lake water samples. Very little acetone is expected to reside 

in soil, biota, or suspended solids. Acetone meets the OECD definition of readily biodegradable, 

which requires that the biological oxygen demand is at least 70 % of the theoretical oxygen 

demand within the 28-day test period. Acetone is rapidly biodegraded in water and this is the 

dominant removal process in the environment.” 

“The volatile nature of acetone will limit the amount that will remain on food crops, and any 

residue that enters the body will be metabolized. In addition to volatilization from soil surfaces, 

acetone biodegrades readily in the soil, which indicates that run-off into surface water from 

pesticidal uses is not expected. Therefore, dietary exposures of concern from food (including 

crops, meats, and fish) and drinking water are not likely from the use of acetone as an inert 

ingredient in pesticide products.” 

Ecotoxicity testing shows that acetone exhibits a low order of toxicity. Acetone has been tested in 

a variety of aquatic and terrestrial species. Acute toxicity to fish ranges from an LC50 of 6,070 

mg/L for Brook trout to 15,000 mg/L for Fathead minnow. The lowest LC50 for aquatic 

invertebrates is 2,100 mg/L ranging to 16,700 mg/L. The NOEC’s for toxicity to aquatic plants 

range from 5,400 – 7,500 mg/L. The chronic NOEC for Daphnia is 1,660 mg/L. Tests using 

Ring-neck pheasant and Japanese quail produced no adverse effects at 40,000 mg/kg.

CUMULATIVE EXPOSURE

Section 408(b)(2)(D)(v) of the Federal Food Drug and Cosmetic Act requires that, when 

considering whether to establish, modify, or revoke a tolerance, the Agency consider “available 

information” concerning the cumulative effects of a particular pesticide’s residues and “other 

substances that have a common mechanism of toxicity.” 

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to 

acetone and any other substances, and these materials do not appear to produce a toxic metabolite 

produced by other substances. For the purposes of this tolerance action, therefore, EPA has not 

assumed that acetone has a common mechanism of toxicity with other substances. For information 

reading EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to 

evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s 

Office of Pesticide Programs concerning common mechanism determinations and procedures for 

cumulating effects from substances found to have a common mechanism on EPA’s website at 

http://www.epa.gov/pesticides/cumulative/. 
Page 18 of 21

VIII. Environmental Justice Statement

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf.

As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups 

according to well-established procedures. In line with OPP policy, RD estimates risks to 

population subgroups from pesticide exposures that are based on patterns of that subgroup’s food 

and water consumption, and activities in and around the home that involve pesticide use in a 

residential setting. Extensive data on food consumption patterns are compiled by the USDA under 

CSFII and are used in pesticide risk assessments for all registered food uses of a pesticide. These 

data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and 

region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized 

subgroups and exposure assessments are performed when conditions or circumstances warrant. 

Whenever appropriate, non-dietary exposures based on home use of pesticide products and 

associated risks for adult applicators and for toddlers, youths, and adults entering or playing on 

treated areas postapplication are evaluated. Further considerations are currently in development as 

OPP has committed resources and expertise to the development of specialized software and 

models that consider exposure to bystanders and farm workers as well as lifestyle and traditional 

dietary patterns among specific subgroups 

HUMAN HEALTH RISK CHARACTERIZATION

The U.S. EPA (2005) said: “Acetone has low toxicity via all routes of exposure. It is an eye 

irritant, but it is not a skin irritant and does not induce sensitization. CNS and minimal 

developmental and teratogenic effects can result but at doses much higher than are expected to 

occur from pesticidal uses. Acetone is not considered to be genotoxic or carcinogenic. Acetone is 

very volatile and appreciable dermal exposure from pesticide use is unlikely. Inhalation exposures 

are expected to be below toxicity levels of concern. Acetone is produced naturally in the human 

body as part of the energy production processes. The ability of humans to naturally produce and 

dispose of acetone may to a large degree explain its relatively low toxicity following external 

exposure to moderate amounts of the liquid or vapor. The volatile nature of acetone and its ready 

biodegradation indicates that residues on food (including crops, meats and fish) and in drinking 

water are unlikely.” Taking into consideration the available information on acetone, there is a 

reasonable certainty that no harm to any population subgroup will result from aggregate exposure 

when considering dietary exposure (including crops, meats and fish) and all other nonoccupational sources of pesticide exposure for which there is reliable information. Therefore, it is 

recommended that acetone be granted an exemption from the requirement of a tolerance when 

used as an inert ingredient in pesticide products applied to animals raised for food under 40 CFR § 

180.930 and it may be considered as safe under § 408(q) of the FFDCA. 
Page 19 of 21

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