Page 2 of 20

of a tolerance under 40 CFR § 180.920. A search of the internet revealed a DRAFT Interim REL 

(Reference Exposure Level) dated March 2010 (California Office of Environmental Health Hazard 

Assessment). No additional “new” information has been identified. 

Non-pesticidal uses of 2-methyl-2,4-pentandediol include use as a chemical intermediate, a 

selective solvent in petroleum refining, a component of hydraulic fluids, a solvent for inks, as an 

additive to cement, use in cosmetics and hair care products, textile dye vehicles, as a lubricant and 

fuel additive. The Food and Drug Administration (FDA) has approved of the use of hexylene 

glycol as an indirect food additive such as in adhesives in contact with food 

(www.cosmeticsinfo.org). 

Hexylene glycol is not acutely toxic to rats via the oral route of exposure. An OECD-SIDS (2001) 

report indicates LD50 ranges from 2 – 4.47 g/kg. A TSCA §8(e) submission indicates the oral 

LD50 in rats ranges from > 500 mg/kg to < 5000 mg/kg. No deaths were reported at 500 mg/kg. 

Acute dermal toxicity is low with dermal doses up to 2000 mg/kg that did not cause death 

(Gardner, 1996 cited in OECD). 

Acute inhalation studies indicate hexylene glycol has low acute inhalation toxicity. Rats exposed 

to 0.31 mg/L hexylene glycol vapor for 1 hour survived and no LC50 was determined (Biofax, 

1970, cited in BIBRA). 

Rabbits treated with 0.1mL undiluted hexylene glycol experienced conjunctival redness and slight 

corneal opacity (Gardner, 1996b, cited in OECD-SIDS). A TSCA §8(e) (1992) submission 

reported severe eye irritation when 0.1mL of hexylene glycol was administered to the conjunctival 

sacs of rabbits. 

Rabbits treated with 0.5mL of undiluted hexylene glycol showed slight, but reversible erythema 

after 72 hours in a 4-hour semi-occlusive dermal irritation study (Parcel, 1995, cited in OECDSIDS). 

A 1992 TSCA § 8(e) submission, a 24 hour covered application of 0.5 mL hexylene glycol to 

rabbit skin, produced slight to moderate erythema and severe erythema at 24 hours. At 72 hours, 

both the erythema and edema were slight to moderate in intensity. 

Garner (1966d cited in OECD-SIDS) noted no positive sensitization responses in a guinea pig 

assay using undiluted hexylene glycol. 

Ward (2005) reported a 90-day subchronic toxicity study with hexylene glycol administered by 

gavage to rats. Doses ranged from 50 – 450 mg/kg bw/day. A functional observational battery 

test gave no indication of neurotoxicity. The NOAEL in this study was 450 mg/kg/day, the highest 

dose tested. 

Hexylene glycol at ≥ 99 % was non-mutagenic in an Ames test with S. typhiumurium as well as E. 

coli (Meyer et al, 1985 and Brooks et al., 1988 – cited in OECD-SIDS). 
Page 3 of 20

There was no reported evidence of cytotoxicity or clastogenicity when hexylene glycol was 

administered to a hamster ovary cell assay at 5000μg/mL. 

Hexylene glycol has low potential for reproductive or developmental toxicity (Ward, 2005; 

Fabreguettes, 199a; Clode, 1997 – cited in OECD-SIDS). In a developmental toxicity study in rats, 

no fetal toxicity was observed at doses up to 300 mg/kg/day. 

No carcinogenicity studies have been identified for hexylene glycol. 

Based upon the available toxicological information the Agency believes there is no concern, at this 

time, for increased sensitivity to infants and children to hexylene glycol when used as an inert 

ingredient in pesticide formulations. Thus, an additional safety factor to protect infants and 

children is not needed. 

No residue data were provided for hexylene glycol. In the absence of data, the Agency has 

developed an approach that uses surrogate information to derive upper bound exposure estimates 

for the subject inert ingredient. There was no hazard attributable to a single exposure seen in the 

toxicity database for hexylene glycol. Therefore, an acute dietary risk assessment was not 

conducted. 

 A chronic dietary risk assessment was conducted using the Dietary Exposure Evaluation 

Model software with the Food Commodity Intake Database (DEEM-FCIDTM, Version 2.03. The 

chronic analysis assumed 100% crop treated, default processing factors and tolerance-level 

residues for all foods and use limitations of not more than 50% by weight in pesticide 

formulations. Drinking water (100 ppb) was incorporated directly into the dietary assessment. 

The chronic dietary risk assessment shows that the chronic dietary risk estimates are not of 

concern (i.e., <100% cPAD). For the U.S. population, the exposure for food and water utilized 

3.8% of the cPAD. The chronic dietary risk estimate for the highest exposed population subgroup, 

children 1-2 years old is 12.5% of the cPAD. RD has not identified any concerns for 

carcinogenicity relating to hexylene glycol, therefore, a cancer dietary exposure assessment was 

not performed. 

An occupational exposure assessment was conducted. In a hypothetical, high-acreage (i.e., high 

volume) situation (1200 acres treated per day), a mixer/loader would have a Margin of Exposure 

(MOE) of approximately 8,000 provided protective gloves were worn with a single layer of work 

clothing (long pants, long-sleeved shirt, shoes plus socks). The estimated MOEs for various 

methods of commercial, agricultural applications ranged from 16,000 to 78,000. 

Post-application exposure was not evaluated quantitativly. In view of a very short environmental 

half life and the restricted entry intervals associated with most pesticide products, post-application 

exposure is considered negligible. 

Hexylene glycol is infinitely soluble in water. It has a low potential to sorb to soils. It is readily 

biodegradable. It is slightly volatile. If released to the atmosphere, the calculated half-life is 9 

hours due to photo-oxidation. OEHHA cites the OECD (2001) as believing hexylene glycol is 

unlikely to persist in the environment. 
Page 4 of 20

Taking into consideration all available information on hexylene glycol, 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 the one exemption from the requirement of a tolerance established for residues 

of hexylene glycol when used as a solvent in pesticide formulations applied to pre- and post 

harvest under 40 CFR 180.910 and direct application to animals under 40 CFR 180.930 can be 

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

INTRODUCTION 

Under provisions in Section 408(d) of the Federal Food, Drug and Cosmetic Act (FFDCA), 21 

U.S.C. 346a(d), the FBSciences, Inc., 153 N. Main Street, Suite 100, Collierville, TN 38017 has 

requested approval by the Environmental Protection Agency (EPA or the Agency) for the 

exemption from the requirements of a tolerance for residues of 2-methyl-2, 4-pentanediol (CAS 

No. 107-41-5) when used as an inert ingredient in pesticide formulations. The request is filed 

under petition number PP0E7693 and docket number EPA-HQ-OPP-2010-0330. The request is to 

amend 40 CFR § 180.910 and § 180.930 to include 2-methyl-2,4-pentanediol (hereafter hexylene 

glycol), without restrictions, as an inert ingredient as a solvent in pesticide formulations. 

The Agency has previously assessed the human health and environmental risks of hexylene glycol 

(Memorandum, 8 November 2005, R. Ward, “Reassessment of the One Exemption from the 

Requirement of a Tolerance for 2-Methyl-2,4-pentanediol (Hexylene glycol)”. The Agency’s 

assessment was in regards to the use of hexylene glycol applied to growing crops prior to crop 

emergence from the soil – exemption from the requirements of a tolerance under 40 CFR § 180-

920. A search of the internet revealed a DRAFT Interim REL (Reference Exposure Level) dated 

March 2010 (California Office of Environmental Health Hazard Assessment). With that 

exception, no new or additional risk assessments have been identified. In support of its request, 

FBSciences relies principally upon the Agency’s 2005 assessment. 

Non-pesticidal uses of hexylene glycol include use as a chemical intermediate, a selective solvent 

in petroleum refining, a component of hydraulic fluids, a solvent for inks, as an additive to cement, 

use in cosmetics and hair care products, textile dye vehicles, as a lubricant and fuel additive. The 

Food and Drug Administration (FDA) has approved of the use of hexylene glycol as an indirect 

food additive such as in adhesives in contact with food (www.cosmeticsinfo.org). 

In 2005, the Agency concluded: “Taking into account all available information on hexylene 

glycol, it has been determined that there is reasonable certainty that no harm to any population 

subgroup will result from aggregate exposure to this chemical when considering dietary exposure, 

and all other non-occupational sources of pesticide exposure for which there is reliable 

information.” 

 
Page 5 of 20

PHYSICAL/CHEMICAL PROPERTIES 

The physical-chemical properties described below are abstracted from NIH (2004). 

Structure

Common Names 2-methyl-2,4-pentanediol; 

 diolane; 

 1,1,3-trimethyltrimethylene-diol; 

 2,4-dihydroxy-2-methylpentane; 

 4-methyl-2,4-pentanediol 

CAS No. 107-41-5 

Formula C6H14O2

Physical state colorless liquid with mild, sweetish odor 

Molecular weight 118.175 

Water solubility 1.00 x 106 mg/L at 25◦ - very water soluble 

Melting point -50◦

 C 

Henry’s Law Constant 4.06 x 10-7 atm-m3/mole @ 25◦ C 

Vapor Pressure 0.013 mm Hg @ 25◦

 C 

Octanol/Water Partition 

 Coefficient Log P = 0.580 

HAZARD ASSESSMENT 

The majority of the remaining discussion in this document is taken directly and primarily from the 

Agency’s 2005 assessment (cited earlier). Exceptions are noted. The Agency’s assessment was 

derived largely from an OECD-SIDS submission (2001), a BIBRA report (1991), a review by 

Cavender and Sowinski in Patty’s Toxicology (2001), and a TSCA submission (1995). As the 

original assessment is available for review, for purposes of the document herein, the discussion is 

abstracted. 

 
Page 6 of 20

Acute Toxicity 

Acute Oral Toxicity - Based on information in the OECD-SIDS report (2001), hexylene glycol 

has low acute oral toxicity. Acute oral toxicity studies with the rat indicate the oral LD50 ranges 

from 2 g/kg to 4.47 g/kg (Gardner 1996a and BIBRA, 1991 as cited in OECD-SIDS). According 

to Gardner, there were no deaths at 2 g/kg and no macroscopic lesions noted at necropsy in the 

majority of rats in the study. 

A TSCA §8(e) submission (1992) indicates the acute oral LD50 in rats is > 500 mg/kg but < 5000 

mg/kg. No deaths were reported at 500 mg/kg but rats did exhibit increased salivation, retching, 

dyspnea and a decrease in activity and limb tone. At 5000 mg/kg, all rats died in the first day after 

exhibiting the same symptoms as the lower dose in addition to marked ataxia, prostration and 

alterations in placing, pinna and corneal reflexes. 

Acute Dermal Toxicity - In a study by Gardner (1996 cited in OECD) hexylene glycol did not 

cause death in rats up to 2000 mg/kg with no macroscopic lesions at necropsy. In a 1992 study 

(TSCA §8(e), there were no deaths in rabbits treated with 200 – 2000 mg/kg. Slight to moderate 

edema and erythema were seen at both doses in the first 24 hours. Throughout the 14-day dosing 

period, both doses induced varying degrees of necrosis, blanching and pus between skin layers. At 

the end, slight to moderate desquamation, leathery skin texture and fissuring were noted in all test 

subjects. 

Acute Inhalation Toxicity – Some older studies suggest the hexylene glycol has low inhalation 

toxicity. Rats exposed to 0.31 mg/L hexylene glycol vapor for 1 hour survived, no LC50 was 

determined (Biofax, 1970 cited in BIBRA). There were no deaths in rats exposed to saturated 

hexylene glycol vapor at a concentration of approximately 160 ppm (0.772 mg/L) (Union Carbide, 

1949, Shell Chemical, 1958, Smyth and Carpenter, 1948 cited in Patty’s Toxicology). No LC50

was determined. 

Eye Irritation – Conjunctival redness and slight corneal opacity occurred in rabbits treated with 

0.1mL undiluted hexylene glycol (Gardner, 1996b cited in OECD-SIDS). Symptoms resolved 

within 3-8 days. The TSCA §8(e) submission (1992) reported severe eye irritation when 0.1mL of 

hexylene glycol was administered to the conjunctival sacs of rabbits. All rabbits had complete 

corneal opacity after 72 hours as well as purulent discharge and marked extreme iridal and 

conjunctival irritation. 

Skin Irritation – Rabbits treated with 0.5 mL of undiluted hexylene glycol showed slight, but 

reversible erythema after 72 hours in a 4-hours semi-occlusive dermal irritation study (Parcel, 

1995 cited in OECD-SIDS). There was no irritation observed following a 24 hour covered 

application of 2000 mg/kg undiluted hexylene glycol (Gardner, 1996b cited in OECD-SIDS). 

In the 1992 TSCA §8(e) submission, a 24 hour covered application of 0.5 mL hexylene glycol to 

rabbit skin, produced slight to moderate erythema and severe edema at 24 hours. At 72 hours, both 

the erythema and edema were slight to moderate in intensity. 
Page 7 of 20

Skin sensitization – Gardner (1966d cited in OECD-SIDS) noted no positive sensitization 

responses in a guinea pig assay using undiluted hexylene glycol with topical induction and 

challenge applications. A challenge was also conducted using a 50 % aqueous solution. 

The summary table is taken from Ward , 2005. Similar findings with regards to acute toxicity are 

found in databases of the United States National Library of Medicine 

(www.chem2.sis.nlm.nih.gov). 

Subacute/Subchronic Toxicity 

As noted and cited by Ward (2005), in a 90-day subchronic toxicity study, hexylene glycol was 

administered by oral gavage to rats at dose levels of 50, 150, or 450 mg/kg bw/day (Fabreguettes, 

1999b, as cited in OECD-SIDS). A functional observational battery test gave no indication of 

Summary of Acute Toxicity Data for Hexylene Glycol

Parameter Toxicity Value Toxicity 

Category 

Comments Reference 

Oral LD50, Rat >2 but <5 g/kg bw III No deaths at 2 g/kg and no macroscopic 

lesions at this dose at necropsy. No other 

information given. 

Gardner, 1996a; 

BIBRA, 1991; 

Industrial Biotest, 

1970; and German 

MAK Commission, 

1997, as cited in 

OECD-SIDS 

Oral LD50, Rat > 0.5 but <5.0 

g/kg bw 

III There were no deaths at 0.5 mg/kg, but all 

rats died at 5 g/kg dose level. 

TSCA 8(e) CP, 1992 

Dermal LD50, Rat > 2 g/kg bw III/IV No deaths at this dose and no macroscopic 

lesions as this dose at necropsy. 

Gardner, 1996b, as 

cited in OECD-SIDS 

Dermal LD50, 

Rabbit 

> 2 g/kg bw III/IV Slight to moderate edema and erythema 

starting at 200 mg/kg, but no deaths. 

TSCA 8(e) CP, 1992 

Inhalation LC50, 

Rat (1 hour) 

> 64 ppm, or 

> 0.31 mg/L 

II/III Rats exposed to this concentration survived. Bio-fax, 1970, as 

cited in BIBRA 

Inhalation LC50, 

Rat (8 hours) 

> 160 ppm, or 

> 0.772 mg/L 

III/IV Rats exposed to saturated vapor survived. Union Carbide, 1949; 

Shell Chemical Co., 

1958; and Smyth, 

and Carpenter, 1948; 

as cited in Patty’s 

Toxicology 

Eye Irritation, 

Rabbit 

0.1 mL II The undiluted material caused irritation of 

conjunctiva and cornea that healed within 8 

days. 

Gardener, 1996b, as 

cited in OECD-SIDS 

Eye Irritation, 

Rabbit 

0.1 mL II The chemical produced severe eye irritation 

and complete corneal opacity after 72 hours. 

TSCA 8(e) CP, 1992 

Dermal Irritation, 

Rat (24 hours) 

2000 mg/kg bw IV Covered application of undiluted chemical for 

24 hours produced no irritation. 

Gardener, 1996b, as 

cited in OECD-SIDS 

Dermal Irritation, 

Rabbit (4 hours) 

0.5 mL III Semi-occlusive exposure to pure chemical 

produced slight to moderate erythema that 

was reversible, and no edema. 

Parcel, 1995, as cited 

in OECD-SIDS 

Dermal Irritation, 

Rabbit (24 hours) 

0.5 mL III Covered application of the chemical produced 

slight to moderate edema and erythema at 72 

hours. 

TSCA 8(e) CP, 1992 
Page 8 of 20

neurotoxicity. In both sexes, hyperplasia, hyperkeratosis, inflammatory cell infiltration and edema 

of the mucosa and submucosa of the stomach were observed starting at 150 mg/kg/day. These 

changes were indicative of a local irritative effect resulting from the oral gavage procedure. 

Hepatocellular hypertrophy with increased liver weight was observed at 450 mg/kg/ day in both 

sexes, and in males at 150 mg/kg/day. In the absence of degenerative or necrotic changes these 

findings were considered to be adaptive responses. At 150 and 450 mg/kg/day, increased kidney 

weights and increased incidence of acidophilic globules in the tubular epithelium in males were 

suggestive of male rat specific alpha-2-microglobulin nephropathy, which is not considered as an 

effect relevant to humans. Observed changes were either fully or partially reversible over the 4-

week recovery period. There were no adverse effects on the reproductive organs. No effects were 

observed at 50 mg/kg/day. A NOAEL of 450 mg/kg/day was determined for systemic toxicity 

because the effects described were either produced by irritation from the oral gavage procedure, or 

were considered adaptive responses. A range-finding 14-day study (Fabreguettes, 1999a, as cited 

in OECD-SIDS) gave similar results. 

 Ten rats and a rabbit exposed to an aerosol of hexylene glycol at a concentration of 0.7 

mg/L (about 145 ppm) for 7 hr/day for 9 days survived with mild upper respiratory irritation. No 

histopathological effects were reported (Union Carbide, 1976, as cited in OECD-SIDS). No 

controls were used and no other details were given in the report. 

 Genotoxicity 

Mammalian and nonmammalian in vitro toxicity studies were reported by Meyer et al, 1985 and 

Brooks et al, 1988 (cited in OECD-SIDS). Hexylene glycol at ≥ 99 % was non-mutagenic in an 

Ames assay in Salmonella typhimurium strains as well as with Escherichia coli. At concentrations 

up to 4000 μg/plate in the presence or absence of metabolic activation, there was no evidence of 

cytotoxicity at any dose level. There was no increase in reverse mutation rate with any of the 

bacterial strains. 

Mitotic gene conversion in Saccharomyces cerevisiae JD1 was measured in a liquid suspension 

assay at concentrations up to 5.0 mg hexylene glycol/mL in the presence or absence of rat liver S9 

fractions. There was no significant effect on cell viability and no increase in the rate of mitotic 

gene conversion according to Meyer et al, 1985 and Brooks et al, 1988 (cited in OECD-SIDS). 

In a hamster ovary cell assay, cultures were treated with hexylene glycol at concentrations up to 

5000μg/mL in the presence or absence of metabolic activation. There was no reported evidence of 

cytotoxicity at any dose level and no increase in the number of chromosome aberrations (ibid). 

 Reproductive/Developmental Toxicity 

According to Ward (2005), no guideline reproduction studies were available for assessment, 

however, no adverse effects on reproductive organs (including testes, prostate, seminal vesicles, 

epididymis, ovaries, vagina, and uterus) were observed in the 90-day gavage study in which rats 

were administered hexylene glycol at doses up to 450 mg/kg/day (Fabreguettes, 1999a, as cited in 

OECD-SIDS). Therefore, OECD SIDS concluded that no additional studies are required under 

the SIDS program regarding fertility. 
Page 9 of 20

In a range finding developmental toxicity study, pregnant rats were administered 30, 300, 

or 1000 mg/kg bw/day of hexylene glycol by gavage in 5 mL/kg of vehicle on gestation days (GD) 

6-15 (Clode, 1997, as cited in OECD-SIDS). The NOAEL for maternal toxicity was 300 

mg/kg/day based on a statistically significant reduction in group mean body weight gain and food 

consumption at 1000 mg/kg/day. There was a marginal, non-statistically significant reduction in 

fetal body weight at 1000 mg/kg/day. Marginally higher incidences of fetal variations, some of 

which were statistically significant (occipitals incompletely ossified, 21.6%; extra thoracolumbar 

ribs, 18.7%; and hyoid arch not ossified, 18%), occurred at 1000 mg/kg/day. A delay in the 

normal ossification process was also observed in fetuses, but this was considered by the authors to 

be related to reduced maternal body weight gain at this dose level. The NOAEL and LOAEL for 

maternal and fetal developmental toxicity were determined to be 300 and 1000 mg/kg/day, 

respectively. 

In another developmental toxicity study, pregnant rats received 500, 1200, or 1600 mg/kg 

bw/day of hexylene glycol by gavage in 10 mL/kg of vehicle on GD 6-17 (TSCA §8(e), 1995). At 

1200 and 1600 mg/kg/day, dams had ataxia and reductions in mean weight gain and food 

consumption. At the 1600 mg/kg/day, pregnant rats had mean weight loss, and one female aborted 

prior to the end of the study. Maternal toxicity at these levels corresponds to decreased fetal body 

weights and gravid uterine weights. Additionally, at 1600 mg/kg/day, there was one abortion and 

one whole litter resorption. However, the number of fetal malformations, such as increased 

incidence of skeletal variations (delayed ossification, extra ribs), was not significantly different 

from controls. A maternal NOAEL of 500 mg/kg/day was determined by the Agency, and the 

same NOAEL was determined in the study for fetal toxicity. These results support the results of 

Clode’s (1997) study described above and indicate that hexylene glycol has low potential for 

developmental toxicity. 

 Carcinogenicity – No carcinogenicity studies have been identified for hexylene glycol. There 

is no evidence that hexylene glycol is carcinogenic. The Agency used a qualitative structure 

activity relationship (SAR) database, DEREK Version 11, to determine if there were structural 

alerts. No structural alerts were identified. In addition, it is negative for mutagenicity in 

mammalian and non-mammalian mutagenicity assays. Hexylene glycol is rapidly metabolized and 

excreted as glucuronates. Based on the above mentioned weight-of-evidence and low toxicity, 2-

methyl-2,4-pentanediol is not expected to be carcinogenic. 

Metabolism: Larsen (1958 cited in OECD-SIDS 2001) reported that male rats receiving 200 

mg/day excreted 40% of the administered dose in the urine, of this about 4% was in the form of 

free glycol. Diechmann & Dierker, (1946 cited in OECD-SIDS 2001), reported a substantial 

increase in the levels of glucuronates in the plasma and urine of rats and rabbits fed hexylene 

glycol. Gessner et al, (1960 cited in OECD-SIDS 2001) also reported excretion of glucuronate in 

the urine of rabbits administered about 118 mg/kg by stomach tube. 67% of the dose was 

recovered from the urine in conjugated form. They were unable to characterize the conjugate. 

These studies clearly indicate that orally administered hexylene glycol is rapidly absorbed, 

metabolized in the body and rapidly excreted as glucuronide conjugates. 
Page 10 of 20

TOXICITY ENDPOINT SELECTION: 

No acute endpoint of concern was identified in the available toxicity studies. The endpoint of 

concern for the chronic reference dose (cRfD) was identified from the developmental toxicity 

study in rats (main study). In this study, the NOAEL (500 mg/kg/day) was based on increased 

incidence of clinical signs, reductions in mean body weight gain and food consumption seen at the 

LOAEL of 1200 mg/kg/day and above. This NOAEL was supported by the 90-day gavage 

toxicity study in rats. There was a lower NOAEL ( 300 mg/kg/day) observed in the range finding 

study in rats based on a statistically significant reduction in group mean body weight gain and food 

consumption, and marginally higher incidences of fetal variations seen at the LOAEL of 1000 

mg/kg/day. The differences between the NOAELs of the range finding study and the main 

developmental toxicity study in rats were considered due to artifacts of dose selection. An 

uncertainty factor 100X (10X for intraspecies variability and 10X interspecies extrapolation) was 

applied to the NOAEL. No additional uncertainty factor is necessary for use of the subchronic to 

chronic study because the effects were observed at the limit dose of 1000 mg/kg/day and above. 

The FQPA factor for increased susceptibility of infant and children was reduced to 1X. Therefore, 

the cRfD is equal to population adjusted dose (cPAD). This endpoint and the dose was also used 

for dermal and inhalation exposure assessment for all exposure scenarios. Inhalation and dermal 

absorption was assumed to be 100%. This approach would provide a highly conservative estimate 

of risk via the dermal and inhalation routes of exposures. 

CONSIDERATION FOR INFANTS AND CHILDREN (FQPA SAFETY FACTOR) 

Section 408(b)(2)(c) of FFDCA provides that EPA shall apply an additional tenfold (10X) margin 

of safety for infants and children in the case of threshold effects to account for prenatal and 

postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA 

determines based on reliable data that a different margin of safety will be safe for infants and 

children. This additional margin of safety is commonly referred to as the FQPA safety factor (SF). 

In applying this provision, EPA either retains the default value of 10X, or uses a different 

additional safety factor when reliable data available to EPA support the choice of a different factor. 

The toxicity database for hexylene glycol is adequate for FQPA assessment and the potential 

exposure is adequately characterized given the low toxicity of the chemical. 

The Agency has previously held that hexylene glycol has low subchronic toxicity, with 

developmental NOAELs ranging from 300 to 500 mg/kg/day. In addition, maternal toxicity 

corresponded with fetal toxicity in developmental studies, suggesting that offspring do not have 

greater sensitivity to hexylene glycol than adults. There were no guideline reproduction studies 

available on hexylene glycol, however, no adverse effects on reproductive organs (including testes, 

prostate, seminal vesicles, epididymis, ovaries, vagina, and uterus) were observed at doses up to 

450 mg/kg/day in a 90-day toxicity study in rats. In addition, the reproductive indices were not 

affected in the two available developmental toxicity studies in rats. No evidence of 

neurobehavioral or neuropathology was seen in a 90-day toxicity study in rats. Therefore, a 

developmental toxicity study in rats is not necessary. No evidence of immunotoxicity was 

observed in the available database, therefore, an immunotoxicity study is not required. The dietary 

food exposure assessment utilizes highly conservative default assumptions and would not 

underestimate the dietary risk to all populations. For the purpose of the screening level dietary risk 
Page 11 of 20

assessment to support this request for an exemption from the requirement of a tolerance for 

hexylene glycol, a value of 100 ppb based on screening level modeling was used for the chronic 

dietary risk assessment. The value of 100 ppb is considered to be a high end, conservative 

assumption that is not likely to underestimate drinking water risks. 

Based on the reasoning presented above. EPA has determined that an additional safety factor is 

not needed to protect the safety of infants and children.

 EXPOSURE ASSESSMENT 

Dietary Exposure 

In evaluating dietary exposure to hexylene glycol, EPA considered exposure under the petitioned 

for exemptions from the requirement of a tolerance. EPA assessed dietary exposure from hexylene 

glycol in food as follows: 

Residues of Concern 

Sufficient data were provided on the chemical identity of hexylene glycol, however, limited data 

are available on the metabolism and environmental degradation of this compound. The Agency 

relied collectively on information provided on the representative chemical structures, the submitted 

physicochemical EPI SuiteTMdata, structure activity relationship information, as well as 

chemicals of similar size and functionality to determine the residues of concern for these inert 

ingredients. The residues of concern for risk assessment purposes are for the parent compound 

only. 

Quantification of Dietary Risk 

Acute 

No endpoint of concern attributed to a single dose was identified in the database. Therefore, acute 

dietary exposure assessment was not required. 

Chronic 

In conducting the chronic dietary exposure assessment, EPA used food consumption information 

from the United States Department of Agriculture (USDA) [1994–1996 and 1998] Nationwide 

Continuing Surveys of Food Intake by Individuals (CSFII). As to residue levels in food, no residue 

data were submitted for hexylene glycol. In the absence of specific residue data, EPA has 

developed an approach, which uses surrogate information to derive upper bound exposure 

estimates for the subject inert ingredient. Upper bound exposure estimates are based on the 

highest tolerance for a given commodity from a list of high-use insecticides, herbicides, and 

fungicides. A complete description of the general approach taken to assess inert ingredient risks in 

the absence of residue data is contained in the memorandum entitled “Alkyl Amines 

Polyalkoxylates (Cluster 4): Acute and Chronic Aggregate (Food and Drinking Water) Dietary 

Exposure and Risk Assessments for the Inerts.” (D361707, S. Piper, 2/25/09) and can be found at 

http://www.regulations.gov in docket ID number EPA-HQ-OPP-2008-0738. 
Page 12 of 20

In the dietary exposure assessment, the Agency assumed that the residue level of the inert 

ingredient would be no higher than the highest tolerance for a given commodity. Implicit in this 

assumption is that there would be similar rates of degradation (if any) between the active and inert 

ingredient and that the concentration of inert ingredient in the scenarios leading to these highest of 

tolerances would be no higher than the concentration of the active ingredient. 

The Agency believes the assumptions used to estimate dietary exposures lead to an extremely 

conservative assessment of dietary risk due to a series of compounded conservatisms. First, 

assuming that the level of residue for an inert ingredient is equal to the level of residue for the 

active ingredient will overstate exposure. The concentration of active ingredient in agricultural 

products is generally at least 50 percent of the product and often can be much higher. Further, 

pesticide products rarely have a single inert ingredient; rather there is generally a combination of 

different inert ingredients used which additionally reduces the concentration of any single inert 

ingredient in the pesticide product in relation to that of the active ingredient. 

Second, the conservatism of this methodology is compounded by EPA’s decision to assume that, 

for each commodity, the active ingredient which will serve as a guide to the potential level of inert 

ingredient residues is the active ingredient with the highest tolerance level. This assumption 

overstates residue values because it would be highly unlikely, given the high number of inert 

ingredients, that a single inert ingredient or class of ingredients would be present at the level of the 

active ingredient in the highest tolerance for every commodity. Finally, a third compounding 

conservatism is EPA’s assumption that all foods contain the inert ingredient at the highest 

tolerance level. In other words, EPA assumed 100 percent of all foods are treated with the inert 

ingredient at the rate and manner necessary to produce the highest residue legally possible for an 

active ingredient. In summary, EPA chose a very conservative method for estimating what level 

of inert residue could be on food, then used this methodology to choose the highest possible 

residue that could be found on food and assumed that all food contained this residue. No 

consideration was given to potential degradation between harvest and consumption even though 

monitoring data shows that tolerance level residues are typically one to two orders of magnitude 

higher than actual residues in food when distributed in commerce. For details, see the Attachment: 

“DEEM-F-CID Chronic Analysis for Hexylene Glycol” (i.e., 2-methyl-2,4-pentandediol). 

Accordingly, although sufficient information to quantify actual residue levels in food is not 

available, the compounding of these conservative assumptions will lead to a significant 

exaggeration of actual exposures. EPA does not believe that this approach underestimates 

exposure in the absence of residue data. 

Cancer 

Since the Agency has not identified any concerns for carcinogenicity relating to hexylene glycol a 

cancer dietary exposure assessment was not conducted. 
Page 13 of 20

Drinking Water Residue Profile 

For the purpose of the screening level dietary risk assessment to support this request for an 

exemption from the requirement of a tolerance for hexylene glycol, a conservative drinking water 

concentration value of 100 ppb, based on screening level modeling, was used to assess the 

contribution to drinking water for the chronic dietary risk assessments for parent compound. These 

values were directly entered into the dietary exposure model. 

 NON- DIETARY EXPOSURE. 

Human exposure to hexylene glycol is expected as a result of commercial uses such as formulation 

of hydraulic fluids, selective solvent in petroleum refining, solvent for inks, additive to cement, 

fuel additive and textile dye vehicles. Regulation of these types of exposures are outside the aegis 

of the FIFRA and regulated by other agencies such as OSHA/NIOSH. 

“Consumer” exposure to hexylene glycol can occur via use in cosmetics and personal care items. 

Negligible exposure may occur via its use in food packaging. According to OECD-SIDS (2001), 

consumer exposure to hexylene glycol is expected through its use in cosmetics, antifreezes and 

hydraulic fluids. It is the Agency’s opinion that exposure from use of antifreezes and hydraulic 

fluids is indeed very limited with the vast majority of the general population never being exposed 

from these uses. Use of such materials is typically not even an annual occurrence. Most persons 

rely upon commercial auto servicing establishments to replenish or maintain appropriate levels of 

these fluids. The Agency believes these are not significant sources of exposure. 

The Agency’s past position (Ward, 2005) was that dietary (food and drinking water) and 

residential (inhalation and dermal) exposures of concern are unlikely with hexylene glycol, 

because it is used in pesticide products that are applied infrequently and because the chemical 

readily biodegrades in the environment. IIAB concurs with that opinion. 

However, it is possible that persons may experience exposure as a result of occupational activities 

such as agricultural or commercial pesticide handlers (i.e., mixers, loaders, applicators). There are 

no compound or product specific data available to the Agency with which to assess exposure and 

risk to occupational pesticide handlers. However, a “screening level” assessment was conducted 

by the Agency based upon assumptions drawn from the Agency’s experience with registering and 

regulating pesticide products. 

In this case, no product label information is available thus certain factors regarding application and 

product density are assumed. The assumptions are by intent, designed to be “conservative” i.e., 

protective. The assessment methodology is that developed and utilized by the Health Effects 

Division’s Science Policy Counsel for Exposure (ExpoSAC). 

For purposes of this screening assessment, the Agency assumes: 

The product density is 8.34 lb/gal 

The rate of application is 4 fl oz product/A 

Hexylene glycol = 50 % of the product formulation. 
Page 14 of 20

Thus: 8.34 lb/gal ÷ 128 fl oz/gal = 0.065 lb/fl oz. And, 0.065 lb/fl oz * 0.5 (% hex.glyc) = 

0.0326 lb hexylene glycol/fl oz. 

And 4.0 fl oz/A * 0.0326 lb hex. glyc/fl oz = 0.13 lb hex.gly/A (application rate). 

See Table 2.0 for a summary of estimated exposures and risks to occupational pesticide handlers 

applying a pesticide product containing 50 % hexylene glycol. The estimates assume 100 % 

absorption via the dermal and inhalation routes of exposure. Dermal and inhalation exposures are 

summed prior to use in calculating the Margins of Exposure. A 60 kg bw is used in calculating the 

average daily exposure. These are extremely conservative (protective) assumptions. 

For purposes of risk assessment, the No Observed Adverse Effect Level is 500 mg/kg bw. It is 

identified from the developmental toxicity study in rats (main study). In this study the NOAEL 

was 500 mg/kg/day based on increased incidence of clinical signs, reductions in mean body weight 

gain and food consumption seen at the LOAEL of 1200 mg/kg/day and above. An uncertainty 

factor 100X (10X for intraspecies variability and 10X interspecies extrapolation) was applied to 

the NOAEL. 

1. Unit Exposures are taken from “PHED SURROGATE EXPOSURE GUIDE”, Estimates of Worker Exposure from The Pesticide 

Handler Exposure Database Version 1.1, August 1998. Dermal = Single Layer Work Clothing No Gloves; Single Layer Work 

Clothing With Gloves; Inhal. = Inhalation. Units = mg a.i./pound of active ingredient handled. 

2. Applic. Rate. = assumed 

3. Units Treated are taken from “Standard Values for Daily Acres Treated in Agriculture”; ExpoSAC SOP No. 9.1. Revised 25 

September 2001; 

4. Average Daily Dose = Unit Exposure * Applic. Rate * Units Treated ÷ 60 kg Body Weight 

5. MOE = Margin of Exposure = NOAEL ÷ ADE. Dermal and Inhalation exposures are summed prior to use in calculating MOE. 

NOAEL = 500 mg/kg bw/day. !00 % absorption via the dermal and inhalation routes of exposure. 

Table 2.0 Summary of Exposure & Risk to Occupational Handlers From 

Applying a Hypothetical Pesticide Product Containing 50 % Hexylene Glycol 

Unit Exposure1

mg ai/lb handled 

Applic. Rate2

lb ai/unit 

Units 

Treated3

Avg. Daily Exposure4

mg ai/kg bw/day 

MOE5

Mixer/Loader – Liquid - Open Pour 

Dermal: 

SLNoGlove 2.9 

SLWithGlove 0.023 

Inhal. 0.0012 

0.13 

lb ai/A 

1200 A/day Dermal: 

SLNoGlove 7.54 

SLWithGlove 0.0598 

Inhal. 0.00312

No Glove 

66 

With Glove 

7946 

Applicator – Ground-boom - Open-cab

Dermal: 

SLNoGlove 0.014 

SLWithGlove 0.014 

Inhal. 0.00074 

0.13 

lb ai/A 

200 A/day Dermal: 

SLNoGlove 0.00606 

SLWithGlove 0.00606 

Inhal. 0.000321

No Glove 

78,357With 

Glove 

78,357 

Applicator - Air-blast - Open Cab 

Dermal: 

SLNoGlove 0.36 

SLWithGlove 0.24 

Inhal. 0.0045 

0.13 

lb ai/A 

40 A/day Dermal: 

SLNoGlove 0.0312 

SLWithGlove 0.0208 

Inhal. 0.00039

No Glove 

15,827With 

Glove 

23,596 

Aerial Applicator (Pilots not required to wear gloves) 

Dermal: 

SLNoGlove 0.005 

Inhal. 0.000068 

0.13 

lb ai/A 

1200 A/day Dermal: 

SLNoGlove 0.013 

Inhal. 0.000177 

No Glove 

37,945 
Page 15 of 20

A MOE of 100 is adequate to protect occupational pesticide handlers from exposures to hexylene 

glycol. The estimated MOEs are all > 100 provided that mixer/loaders using open pour loading 

wear protective gloves. Therefore the proposed use as an inert ingredient does not exceed the 

Agency’s level of concern. 

Post-application Exposure. 

A post-application exposure assessment has not been conducted. In view of the very short 

environmental half-life combined with the restricted entry interval on the vast majority of pesticide 

products leads IIAB to believe that post-application exposure is negligible. It would not be 

expected to equal or exceed the exposures estimated for occupational pesticide handlers therefore 

it is not expected to exceed the Agency’s level of concern. 

Aggregate Exposures 

In examining aggregate exposure, the FFDCA section 408 directs EPA to consider available 

information concerning exposures from the pesticide residue in food and all other 

nonoccupational exposures, including drinking water, from ground water or surface water and 

exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses). 

For hexylene glycol, a qualitative assessment for all pathways of human exposure (food, drinking 

water, and residential) is appropriate given the lack of human health concerns associated with 

exposure to hexylene glycol as an inert ingredient in pesticide formulations. 

For the following reasons, a quantitative assessment of non-occupational exposures was not 

conducted. 

1). The toxicological endpoint chosen as a point of reference is highly conservative. The NOAEL 

of 500 mg/kg bw/day was identified from arat developmental toxicity study in which the maternal 

effects were marginal i.e., reduced group mean body weight gain and food consumption at a dose 

of 1,200 mg/kg bw/day and above. A number of additional studies indicate no toxicological 

effects up to doses of 450 mg/kg bw/day. 

2). A quantitative exposure and risk assessment for residential uses was not conducted. An 

assessment of occupational exposures was conducted assuming high rates of application; 100 % 

dermal and inhalation absorption and high volumes of material applied per day. The lowest 

Margin of Exposure (8,000) was for a mixer/loader. MOEs for high exposure methods of 

commercial scale agricultural application ranged from 16,000 – 78,000. The Agency believes it is 

not likely that residential exposure(s) would exceed those assessed for occupationally exposed 

individuals. 

3). Dietary exposure (food and water) was assessed assuming 100% level of tolerance residue, 100 

% of the crop(s) were treated and an occurence of 50 % of the formulation being the inert 

ingredient. There was no hazard attributable to a single exposure seen in the toxicity database for 

hexylene glycol. Therefore, the hexylene glycol is not expected to pose an acute risk. A chronic 

aggregate risk assessment takes into account exposure estimates from chronic dietary consumption 

of food and drinking water. The chronic dietary exposure from food and water to hexylene glycol 
Page 16 of 20

is 3.8 % of the cPAD for the U.S. population and 12.5 % of the cPAD for children 1-2 yrs old, the 

most highly exposed population subgroup. The Agency has not identified any concerns for 

carcinogenicity relating to hexylene glycol 

 

In view of the results from the screening level exposure assessments which were based upon 

highly conservative (i.e., protective) assumptions, the Agency believes a quantitative assessment is 

not necessary. The Agency believes that any non-occupational exposures that might occur would 

be of much smaller magnitude due to the expected small volumes of material that might be 

handled or contacted, and to the fact that residential products are typically diluted to a fraction of 

what was assumed and used in the occupational assessments. The Agency believes these factors 

are protective to persons who might experience non-occupational exposures. 

 CUMULATIVE EXPOSURE

Section 408(b)(2)(D)(v) 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.” 

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 

hexylene glycol and any other substances, and this material does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA 

has not assumed that hexylene glycol has a common mechanism of toxicity with other substances. 

For information regarding 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. 

 ENVIRONMENTAL FATE CHARACTERIZATION 

Hexylene glycol can be released into the environment from various industrial sources, wastewater 

effluents from wastewater treatment plants, and its use as an inert ingredient in pesticide products. 

Biological screening studies (Blok, 1985, as cited in OECD-SIDS) have demonstrated that 

hexylene glycol readily biodegrades. It is infinitely water soluble, and has low potential to sorb to 

soil, so it is likely to leach from soil and distribute primarily to water. Leaching to groundwater, 

although likely under certain conditions, will be reduced due to the compound’s biodegradability. 

Releases to surface water will undergo substantial biological degradation prior to reaching 

drinking water intakes. As a result, concentrations in drinking water are likely to be below the low 

parts per billion. Hexylene glycol is slightly volatile (0.013 mm Hg @ 25oC). If released to the 

atmosphere, the chemical has a calculated half-life of 9 hours due to photo-oxidation (OECD-SIDS 

2001). 

Similar conclusions are presented in a March 2010 draft Interim Reference Exposure Level 

document (www.oehha.org.ca.gov). The California Office of Environmental Health Hazard 
Page 17 of 20

Assessment utilized the EPA’s EPIWIN/APO model to assess environmental effects from 

exposures to hexylene glycol. The estimated atmospheric photodegradation (reaction with 

hydroxyl radicals) half-life of hexylene glycol is 9 hours, based on a 12 hours sunlight/day. 

Glycols have no hydrolysable groups and are generally not susceptible to hydrolysis in water under 

neutral conditions at ambient temperatures. The estimated Henry’s Law Constant of 2.94 x 10-8

atm-m3/mole for hexylene glycol indicates it has limited potential to partition from water to air. 

The environmental distribution of hexylene glycol, as predicted by Mackay level I fugacity 

modeling, is 0.169% in air, 99.5% in water, 0.335% in soil, and 0.0074% in sediment. Although 

there are insufficient experimental data to determine whether hexylene glycol is readily 

biodegradable, it is considered at least inherently biodegradable. With a predicted 

bioconcentration factor of 3.162 and Log KOW of 0.58, hexylene glycol is not expected to 

bioaccumulate. Hexylene glycol is therefore unlikely to persist in the environment (OEHHA cites 

OECD 2001). 

Human Health Risk Characterization

IIAB agrees with the summary presented by Ward (2005). No additional information has been 

identified which would cause the Agency to modify its assessment of hexylene glycol. Hexylene 

glycol is low in acute oral and dermal toxicity, with LD50 values in excess of 2000 mg/kg. It is 

irritating to the eye and skin, but is not a skin sensitizer. It has low inhalation toxicity, with an 

inhalation LC50 (>160 ppm, or 0.772 mg/L) that is in excess of the saturated vapor concentration. 

In addition, the vapor pressure is sufficiently low at normal temperatures so that it does not present 

an inhalation hazard. The chemical is also not genotoxic in either mammalian or non-mammalian 

cells in vitro. Developmental toxicity occurred at high doses in studies, with maternal and 

developmental NOAELs ranging from 300 to 500 mg/kg/day. 

No residue data were provided for hexylene glycol. In the absence of data, the Agency has 

developed an approach that uses surrogate information to derive upper bound exposure estimates 

for the subject inert ingredient. There was no hazard attributable to a single exposure seen in the 

toxicity database for hexylene glycol. Therefore, an acute dietary risk assessment was not 

conducted. 

 A chronic dietary risk assessment was conducted using the Dietary Exposure Evaluation 

Model software with the Food Commodity Intake Database (DEEM-FCIDTM, Version 2.03. The 

chronic analysis assumed 100% crop treated, default processing factors and tolerance-level 

residues for all foods and use limitations of not more than 50% by weight in pesticide 

formulations. Drinking water (100 ppb) was incorporated directly into the dietary assessment. 

The chronic dietary risk assessment shows that the chronic dietary risk estimates are not of 

concern (i.e., <100% cPAD). For the U.S. population, the exposure for food and water utilized 

3.8% of the cPAD. The chronic dietary risk estimate for the highest exposed population subgroup, 

children 1-2 years old is 12.5% of the cPAD. RD has not identified any concerns for 

carcinogenicity relating to hexylene glycol, therefore, a cancer dietary exposure assessment was 

not performed. 

Taking into consideration all available information on hexylene glycol, there is a reasonable 

certainty that no harm to any population subgroup will result from aggregate exposure when 
Page 18 of 20

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 the one exemption from the requirement of a tolerance established for residues 

of hexylene glycol when used as a solvent in pesticide formulations applied to growing crops preand post-harvest 40 CFR 180.910 and for use on animals under 40 CFR 180.930 can be considered 

reassessed as safe under section 408(q) of the FFDCA. 

Ecotoxicity and Ecological Risk Characterization

Hexylene glycol is classified as practically non-toxic, according to OPP's classification scheme, to 

aquatic organisms, with the LC50/EC50 being in excess of 2,800 mg/L (NIH 2004). A toxicity test 

on frog tadpoles (Rana catesbiana) produced an LC50 of 11,800 mg/L, which suggests low toxicity 

of this substance to this group of sensitive aquatic organisms. The chemical is also of low toxicity 

to algae, with a 72-hour EC10 and EC50 of >429 mg/L for the algae Slenastrum capricornutum. 

Based on the log Kow of 0.58, it has low potential to bioaccumulate (BCF = 3.162, as calculated 

using the Syracuse Aopwin V1.85 model, OECD-SIDS 2001). Because of hexylene glycol’s low 

potential for bioaccumulation and low toxicity in terrestrial and aquatic organisms, it is unlikely to 

be a risk concern to nontarget species at application rates anticipated in pesticide formulations. 

IIAB concurs with the assessment presented by Ward (2005). 
Page 19 of 20

ATTACHEMENT 

DEEM FCID Chronic Analysis for Hexylene glycol 

U.S. Environmental Protection Agency Ver. 2.00 

DEEM-FCID Chronic analysis for HEXYLNE GLYCOL (1994-98 data) 

Residue file name: C:\Documents and Settings\adebesai\My Documents\hexylne glycol 

500mg kg day.R98 

Adjustment factor #2 NOT used. 

Analysis Date 04-14-2011/17:48:22 Residue file dated: 04-14-2011/16:35:47/8 

Reference dose (RfD, Chronic) = 5 mg/kg bw/day

NOEL (Chronic) = 500 mg/kg bw/day 

COMMENT 1: Inert 57 active ingredients + drinking water (100ppb) 

=============================================================================== 

 Total exposure by population subgroup 

------------------------------------------------------------------------------- 

 Total Exposure 

 ----------------------------------- 

 Population mg/kg Margin of Percent 

 Subgroup body wt/day Exposure 1/ of RfD 

-------------------------------------- ------------- ---------- --------- 

U.S. Population (total) 0.191509 2,611 3.8% 

U.S. Population (spring season) 0.195512 2,557 3.9% 

U.S. Population (summer season) 0.193733 2,581 3.9% 

U.S. Population (autumn season) 0.188144 2,658 3.8% 

U.S. Population (winter season) 0.188739 2,649 3.8% 

Northeast region 0.208249 2,401 4.2% 

Midwest region 0.190460 2,625 3.8% 

Southern region 0.171478 2,916 3.4% 

Western region 0.209414 2,388 4.2% 

Hispanics 0.201698 2,479 4.0% 

Non-hispanic whites 0.187723 2,663 3.8% 

Non-hispanic blacks 0.185288 2,698 3.7% 

Non-hisp/non-white/non-black 0.246967 2,025 4.9% 

All infants (< 1 year) 0.397082 1,259 7.9% 

Nursing infants 0.212711 2,351 4.3% 

Non-nursing infants 0.467077 1,070 9.3% 

Children 1-6 yrs 0.495834 1,008 9.9% 

Children 7-12 yrs 0.239839 2,085 4.8% 

Females 13-19 (not preg or nursing) 0.138939 3,599 2.8% 

Females 20+ (not preg or nursing) 0.149292 3,349 3.0% 

Females 13-50 yrs 0.154523 3,236 3.1% 

Females 13+ (preg/not nursing) 0.163842 3,052 3.3% 

Females 13+ (nursing) 0.192592 2,596 3.9% 

Males 13-19 yrs 0.148194 3,374 3.0% 

Males 20+ yrs 0.144142 3,469 2.9% 

Seniors 55+ 0.152430 3,280 3.0% 

Children 1-2 yrs 0.624005 801 12.5% 

Children 3-5 yrs 0.461958 1,082 9.2% 

Children 6-12 yrs 0.255310 1,958 5.1% 

Youth 13-19 yrs 0.144122 3,469 2.9% 

Adults 20-49 yrs 0.144401 3,463 2.9% 

Adults 50+ yrs 0.152076 3,288 3.0% 

Females 13-49 yrs 0.145389 3,439 2.9% 

------------------------------------------------------------------------------- 
Page 20 of 20

REFERENCES 

BIBRA. 1991. Toxicity Profile: Hexylene glycol. British Industrial Biological Research 

 Association, Surrey, UK. 

California Office of Environmental Health Hazard Assessment. 2010. March 2010 draft Interim 

Reference Exposure Level document (www.oehha.org.ca.gov). 

Cavender, F.L. and Sowinski, E.J. 2001. Glycols. Patty’s Toxicology, 5th Edition. John Wiley 

 and Sons, Inc., New York. Vol. 7, Ch.14, pp. 48-51. 

Cosmetics Ingredient Review. 1985. Final report on the safety assessment of butylenes glycol, 

 Hexylene glycol, ethoxydiglycol, and dipropylene glycol. J. Am. Coll. Toxicol. Vol. 4, No.5 

 pp. 223-248. 

Cosmetics INFO.org. 2010. Hexylene Glycol. www.cosmeticsinfo.org/ingredient 

NIH. 2004. ChemID Plus. U.S. National Library of Medicine. National Institutes of Health, 

 Department of Health & Human Services. Last modified: September 9, 2004. 

http://chem.sis.nlm.nih.gov/chemidplus/

Ibid. 2010. Update 30 March 2010. 

OECD-SIDS. 2001. Organisation for Economic Cooperation and Development-Screening 

Information Data Set (SIDS Initial Assessment report and SIAR Publication; UNEP 

Publications). Hexylene glycol CAS No. 107-41-5. OECD Integrated High Production 

Volume (HPV) Chemical Database. <http://cs3-hq.oecd.org/scripts/hpv/> 

TSCA 8(e) CP No. 8EHQ-1092-12673. Microfiche No. OTS0572003. 1992. Initial Submission: 

 Acute Toxicity Studies in Rats and Rabbits with DM 7664 with Cover Letter Dated 101292. 

 Elf Atochem North America Inc. 

TSCA 8(e) No. 8EHQ-1195-13392. Microfiche No. OTS0572134-1. 1995. Support: Draft 

 Summary of Results of Range-Finding Toxicity Study with 2-Methyl-2,4-Pentanediol in 

 Rats, with Cover Letter Dated 11/22/95. 

Ward, R. Tracy. 2005. Reassessment of the One Exemption from the Requirement of a Tolerance 

for 2-Methyl-2,4-pentanediol (Hexylene glycol). EPA/OPP Memorandum. November 8. 

cc:M.Dow(IIAB) 

RDI: P. Shah; Toxicol Rev. P. Shah 

M.I.Dow:S7958:PY1:(703)305-5533:IIAB:7505P