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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: PV Shah, (703) 308-1846

Huntsman Corporation.

IN-10748

EPA has received a pesticide petition ([IN-10748) Huntsman

Corporation, 8600 Gosling Road, The Woodlands, TX, 77381 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 an exemption from the requirement of a 

tolerance for benzyl acetate, CAS No.: 140-11-4, when used in pesticide formulations 

applied to growing crops under 40 CFR 180.920. 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 NA Remove.

1. Plant metabolism.NA Remove

2. Analytical method. NA Remove

3. Magnitude of residues. NA Remove

B. Toxicological Profile

1. Acute toxicity. Benzyl acetate is low in acute toxicity following exposure of 

rats by the oral route. The acute oral LD50 is 2,490 to 3,690 mg/kg. Benzyl acetate is 

also low in toxicity by the dermal route. The acute dermal LD50 in rabbits is > 5,000 

mg/kg. Rats exposed by the inhalation route to the maximum attainable vapor 

concentration of 766 μg/L benzyl acetate for 4 hours exhibited no clinical signs of 

toxicity on the day of exposure or during the two week follow-up period. The LC50 was 

greater than 766 μg/L. Well-defined erythema was seen following a four-hour dermal 

exposure of rabbits to 0.5 ml of benzyl acetate that cleared by the end of the 7-day study. 

Benzyl acetate is minimally irritating to the eyes. The potential for benzyl acetate to 

cause skin sensitization was evaluated in guinea pigs using a variety of test methods, and 

was determined not to be a sensitizer. 

2. Genotoxicty. Benzyl acetate has been studied in a variety of bacterial and 
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mammalian cell genotoxicity studies as well as in vivo genotoxicity studies. Most of the 

genotoxicity studies on benzyl acetate have been negative, though a few positive results 

have been observed. Negative in vivo studies include two micronucleus assays, a sister 

chromatid exchange assay, and an unscheduled DNA synthesis assay. The weight of the 

evidence from all of the available genotoxicity studies indicates that benzyl acetate is not 

a genotoxic agent. 

3. Reproductive and developmental toxicity. The potential for developmental 

toxicity from exposure to benzyl acetate was evaluated in rat dams. Groups of dams 

received doses of 0, 10, 100, 500 or 1000 mg/kg/day benzyl acetate by gavage days 6 

through 15 of gestation. The data show a decrease in body weight gain of 9.9% occurred 

in the high dose dams compared to vehicle controls throughout exposure from gestation 

day 6 through 20. There were no effects of treatment on corpora lutea, live fetuses, preor post-implantation loss, resorptions, sex ratio, or the mean number of fetuses per dam. 

Fetal body weights were significantly reduced in the high dose group compared to 

controls. The authors concluded that benzyl acetate is not a teratogen, and increased 

incidences of skeletal and internal variations were due to reduced growth and reflected 

the decreased fetal body weight. The maternal and fetal NOAELs for this study were 

both 500 mg/kg/day based on a decrease in body weight in dams and offspring at 1000 

mg/kg/day.

4. Subchronic toxicity. Ten male and ten female rats per dose were fed benzyl 

acetate in the diet at concentrations that corresponded to 0, 230, 460, 900, 1750, or 3900

mg/kg/day for male rats or 0, 240, 480, 930, 1870, or 4500 mg/kg/day for female rats for 

13 weeks. Eighteen of the 20 rats in the high dose groups died between weeks 2 and 8 of 

the study. There was a significant decrease in body weight and food consumption

compared to controls in the 1750 mg/kg/day group males and the high dose males and 

females. There was a benzyl acetate associated decrease in cholesterol level in female 

rats in the 1870 and 930 mg/kg/day groups compared to controls. Testicular seminiferous 

tubular atrophy of mild severity was reported in one male rat in the 900 mg/kg/day group 

and with greater severity in two males the 1750 group. 

5. Chronic toxicity. Benzyl acetate has been evaluated for carcinogenicity by 

IARC and was found to be “not classifiable as to its carcinogenicity to humans (Group 

3).” The evaluation was largely based on the results of bioassays conducted by the 

National Toxicology program (NTP). The NTP conducted two 2-year studies on benzyl 

acetate in both rats and mice. The first study was a gavage exposure study and the 

second was a dietary exposure study. In the second NTP bioassay of benzyl acetate, 

groups of 60 male and female F344/N rats received benzyl acetate in the diet at 

concentrations that provided doses of 0, 130, 260 and 510 mg/kg/day for males and 0, 

145, 290, and 575 mg/kg/day for females. After the chronic exposures, the average body 

weights of the high dose males and females were approximately 5% below the controls, 

and there were no clinical signs of toxicity in any of the groups. There were no 

significant neoplastic or non-neoplastic lesions associated with test article treatment in 

any dose group. A similar chronic dietary exposure study was conducted in B6C3F1 

mice that received 0, 35, 110 or 345 mg/kg/day benzyl acetate for males and 0, 40, 130, 

and 375 mg/kg/day for females. Throughout the study the high dose male and female 
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mouse body weights were 10 to 16% lower than controls, but subjects exhibited no 

clinical signs of toxicity. There were no significant neoplastic or non-neoplastic lesions 

associated with test article treatment in any dose group. 

6. Animal metabolism. Benzyl acetate is readily absorbed from the gastrointestinal 

tract, lungs, and skin, in experimental animals and is rapidly hydrolyzed to benzyl alcohol 

and acetate. Benzyl alcohol is further oxidized to benzoic acid and after conjugation with 

glycine is excreted in the urine as hippuric acid. Minor amounts of benzyl alcohol and 

benzyl mercapturic acid (N-acetyl-S-benzyl-L-cysteine) have been detected in the urine, 

but more than 90% of the urinary metabolite is hippuric acid. Approximately 1 to 1.5 % 

of benzyl acetate is eliminated in the feces. No parent compound is detected in 

experimental animals after exposure. Since metabolism of the primary hydrolysis 

product of benzyl acetate, benzyl alcohol, is very similar in humans and rodents it is 

expected that the metabolism of benzyl acetate in humans is very similar to that in 

rodents

7. Metabolite toxicology. N/A Remove

8. Endocrine disruption. In the available toxicity studies on benzyl acetate, there 

was no toxicologically significant evidence of endocrine disruptor effects. In the 13-

week NTP study, mild to moderate aspermatogenesis was identified in two male rats of 

the 3,900 mg/kg group. Atrophy of the seminiferous tubules was reported in two of ten 

1,750 mg/kg/day males and mild atrophy occurred in one of the 900 mg/kg/day dose 

males. These effects occurred at high doses and decreased in incidence and severity with 

decreasing dose.

C. Aggregate Exposure

1. Dietary exposure. The estimated dietary exposure to benzyl acetate and its salts 

was determined using methods to estimate chronic dietary exposure for a generic inert 

ingredient. This assessment considers drinking water and crop-specific residues from 

pre-harvest applications of agricultural insecticides, herbicides and fungicides, assuming 

the highest established tolerance level residue for each commodity. The assessment 

assumes that the inert ingredient is used on all crops, and that 100% of all crops are 

treated with the inert. The inert ingredient is assumed to be present in all commodities 

treated with 57 of the most significant active ingredients at the maximum tolerance level 

as identified by the U.S. EPA for the default assessment. Chronic dietary exposure 

estimates were derived for the general US population and sub-groups of the population 

using the Dietary Exposure Evaluation Model, DEEMTM. The I-DEEM residue data set 

developed by EPA was used for the analysis. The estimated chronic exposure for the total 

US population is 0.189 mg/kg/day, 3.8% of the chronic Population Adjusted Dose 

(cPAD). Children age 1 to 2 years old have the highest estimated exposure at 0.706

mg/kg/day, 14.1% of the cPAD.

i. Food. Benzyl acetate is a direct food additive approved by the U.S Food and 

Drug Administration (21 CFR 172.515), and it is a naturally-occurring component of a 

variety of fruits and vegetables and other foods. Dietary exposure may occur from use as 
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direct food additive and from consumption of foods that contain naturally-occurring 

benzyl acetate. The maximum likely ingestion from use as a direct food additive is 14 

μg/kg/day (0.014 mg/kg/day). 

ii. Drinking water. Benzyl acetate exposure via drinking water from use as an 

inert ingredient is not expected to be significant. Based on the physical chemical 

characteristics of benzyl acetate, the compound is expected to partition primarily to the 

soil, and the comparatively small amounts that enter the water will readily biodegrade. 

Exposure via the drinking water was estimated in the DEEM dietary exposure assessment 

assuming a concentration of 100 ppb. 

2. Non-dietary exposure. Dermal exposure to consumers is common as a result of 

use of benzyl acetate in cosmetic products, particularly in perfumes, lotions, and soaps. 

Benzyl acetate is generally added as a fragrance ingredient. Most cosmetic products 

contain only a very small amount of benzyl acetate as a fragrance. 

D. Cumulative Effects

Section 408(b)(2)(D) (9v) of the FFDCA 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.” EPA has not made a common 

mechanism of toxicity finding as to benzyl acetate and other compounds. Benzyl acetate 

does not appear to produce toxic metabolites in common with other substances. For the 

purpose of the tolerance exemption actions proposed, it is assumed that benzyl acetate 

does not share a common mechanism of toxicity with other substances.

E. Safety Determination

1. U.S. population. There is a reasonable certainty that no harm to humans will 

result from the use of benzyl acetate as an inert ingredient in pesticide products. A 

NOAEL of 500 mg/kg/day in a developmental toxicity study of rats exposed to benzyl 

acetate was used to derive the chronic population adjusted dose (cPAD). Intraspecies and 

interspecies uncertainty factors were combined for a total uncertainty factor of 100. The 

resulting benzyl acetate cPAD is 5 mg/kg/day. For the total US population, the estimated 

chronic dietary exposure from food and drinking water for benzyl acetate, calculated as 

50% of all agricultural formulations, is 3.8 % of cPAD. This estimated exposure to 

benzyl acetate is well below any level of potential concern. 

2. Infants and children. There is a reasonable certainty that no harm to infants and 

children will result from the use of benzyl acetate as an inert ingredient in pesticide 

products. A developmental toxicity study in rats demonstrated that developmental delay

secondary to decreased fetal body weight occurred only at a maternally toxic dose. A 

cPAD of 5 mg/kg/day derived for benzyl acetate was based on this endpoint that is 

protective of infants and children. The estimated chronic dietary exposure from food and 

drinking water was highest (14% of cPAD) for children aged 1 to 2 years old. Estimated 
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exposure of all infants to benzyl acetate, assuming that benzyl acetate makes up 50% of 

all agricultural formulations, is 7.9% of the cPAD. These estimated exposures to benzyl 

acetate are well below any level of potential concern. 

F. International Tolerances

N/A Remove