Page 2 of 14 principally on the Agency’s 2006 analysis. No new data have been received by the Agency which might alter the conclusions presented in the 2006 Re

- Registration Eligibility Document. Propylene glycol has an extensive database of acute, subchronic, chronic, developmental, and reproductive toxicity, carcinogenicity, mutagenicity, metabolism/pharmac okinetics and dermal toxicity studies

.

EPA (2006) concluded that there are no toxicity endpoints of concern for oral, dermal, or inhalation exposure to propylene glycol. This conclusion is based on the results of toxicity testing of propylene glycol at d ose levels near or above testing limits (as established in the OPPTS 870 series harmonized test guidelines).

The acute oral and dermal toxicity of propylene glycol is low (toxicity category IV). The LD 50

was > 80 00 mg/kg in the rat , mouse, rabbit and guin ea pig (oral). Propylene glycol is non

- irritating to the eyes and skin in rabbits . It is not a dermal sensitizer.

In a 15

- week and 2 year oral toxicity studies , rats were fed a diet containing up to 50,000 ppm ( approximately 2,500 mg/kg bw/day) propyle ne glycol. Treatment related effects w ere not
observed in either study

. Also, systemic toxicity was not observed in dogs treated with up to 5000 mg/kg bw/da y propylene glycol for 2 years. An increased incidence of tumor formation was not

observed in eit her 2 year carcinogenicity study in rats or dogs.

Propylene glycol was evaluated in an In Vivo teratology screening study and continuous breeding study in mice. Propylene glycol was administered by oral gavage and drinking water at a dose rate

up to 10, 1 00 mg/kg bw/day. Neither maternal, developmental nor reproduction effects were seen

at doses as high as 10, 1 00 mg/kg bw/day, a dose that is 10 times higher than the limit dose of 1,000 mg/kg bw/day

.

In a 12 week, repeat dose, dermal toxicity study on fem ale Swiss mice were tested at 100 %, 50 %

and 10 % (approximately 100 ,000; 50 ,000 and 10 ,000 mg/kg/day) concentration propylene glycol. Neither systemic toxicity nor a statistically significant increase in skin tumor incidence was

observed.

Propylene glycol was not mutagenic or genotoxic on the basis of a battery of studies that included the bacterial gene mutation assay using Salmonella typhimurium (AMES) in vitro

assay , in vitro Chinese hamster ovary (CHO) mutation assay, Chinese hamster ovary (CHO) chromosomal aberration assays, and an in vitro sister chromatid exchange assay.

EPA c oncluded that propylene glycol was negative for carcinogenicity in studies conducted up to the testing limit doses established by the Agency; therefore no further carcin ogenic analysis was required.

Neurotoxicity and Immunotoxicity studies were not available in the database. However, no evidence of neurotoxicity or immunotoxicity was present in the submitted studies.

Propylene glycol should be readily metabolized to la ctic acid at the typical low

- level exposures associated with the already approved pesticide inert ingredient registrations under 40 CFR §180.910 and 40 CFR §180.930 uses, and the intended 40 CFR §180.940(a) use in antimicrobialPage 3 of 14 formulations. At higher con centrations (absorbed doses), propylene glycol is primarily excreted unchanged in the urine.

EPA concluded that t he FQPA Safety Factor should be removed (i.e., reduced to 1X) for propylene glycol, because there is no pre

- or post

- natal evidence for increa sed susceptibility following

exposure

.

Since there is no indication of toxicity at the limit dose, a toxicological endpoint of concern for risk assessment purposes, was not identified. Therefore, a quantitative dietary exposure risk assessment for propyl ene glycol is not necessary.

An aggregate assessment was not conducted for exposures through food, drinking water and residential exposure since toxicological endpoints for risk assessment were not identified based on

the available data. In reaching this determination, EPA considered the available information on the special sensitivity of infants and children, as well as aggregate exposure. The inclusion of the uses supported by expanding the current 40 CFR §180.910 and §180.930 tolerance exemptions to

i nclude uses cited at 40 CFR §180.940(a) should not change this determination.

The Agency believes that amending the existing tolerance exemption to include 40 CFR § 180.940(a) will not significantly/measurably increase occupational exposure. The change i n use pattern would be expanded to include food contact surfaces such as tableware, utensils, dairies and beverage and food processing plants. I n view of the regulatory history of propylene glycol, i.e., approved use under 40 CFR § 180.910 and § 180.930 a nd no new toxicological information to indicate otherwise, it is not necessary to quantitatively assess occupational exposure.

UNEP (2001) has summarized propylene glycol’s environmental fate characteristics and its toxicity to aquatic organisms:

• Propylen e glycol is not volatile and it is miscible with water.

• The concentrations of propylene glycol in the atmosphere are expected to be extremely low because of its low vapor pressure and high water solubility.

• Propylene glycol is readily biodegraded in wate r or soil. Four studies reported >60% biodegradation in water in 10 days.

• Propylene glycol is not expected to bioaccumulate. The calculated Bio

- Concentration Factor ( BCF) is <1.

• Propylene glycol is not acutely toxic to aquatic organisms except at very h igh concentrations that would exceed the intended use as a pesticide inert ingredient according to the current 40 measured freshwater aquatic toxicity data of propylene glycol to fish, daphnia, and algae, have

LC/EC 50 ’s that exceed values of >18,000 mg/l ( 18,000 ppm). Additionally, using an

assessment factor of 100 and the Ceriodaphnia data (48

- hour EC 50 = 18,340 mg/l), the Predicted No Effect Concentration ( PNEC ) is 183 mg/l.

Potential areas of environmental justice concerns, to the extent possible, wer e considered in this human health risk assessment, in accordance with U.W. Executive Order 12898 “Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations” http://www.eh.doe.gov/oepa/guidance/justice/eo 12898.pdf.Page 4 of 14 Based on the information summarized above the Agency approves of the use of Propylene Glycol without limitation as an inert ingredient in antimicrobial pesticide formulations applied to “food contact surfaces in public eating places, dairy processing equ ipment, and food processing equipment and utensils” as described in 40 CFR § 180.940(a).

II. BACKGROUND

This is the Decision Document for the proposed use of Pr opylene Glycol (CASRN 57

- 55

- 6; PC Code 868603) as an inert ingredient in antimicrobial pestici de products applied to food contact surfaces and food processing equipment. Specifically, Ecolab, Inc. (370 N. Wabasha Street, St. Paul, MN 55102) is requesting the Environmental Protection Agency approve of the use of Propylene Glycol under 40 CFR § 180. 940(a) as an inert ingredient in antimicrobial pesticide products which may be applied to “food contact surfaces in public eating places, dairy processing equipment, and food processing equipment and utensils.”

Currently, Propylene Glycol is exempt from t he requirements of a tolerance under 40 CFR §180.910 (pre

- and post

- harvest crop uses) and 40 CFR § 180.930 (direct application to animals). It is approved by the Food and Drug Administration under 21 CFR § 184 for Direct Food

Substances Affirmed as Gener ally Recognized as Safe (GRAS).

In September, 2006, the EPA published the “Reregistration Eligibility Decision for Propylene Glycol and Dipropylene Glycol” (EPA Publication EPA

- 739

- R

- 06

- 002; U.S. EPA Office of Prevention, Pesticides and Toxic Substances). The toxicological database for propylene glycol is extensive and is complete.

Much of the discussion of propylene glycol is taken from the Agency’s 2006 publication and portions are taken from the Registrant’s petition.

III. PHYSICAL/CHEMICAL PROP ERTIES

Propylene glycol belongs to a class of organic compounds called diols, which includes compounds with two hydroxy groups as part of their chemical functionality. Propylene glycol is a colorless, nearly odorless, clear, viscous, hydroscopic liquid w ith a faintly sweet taste. The compound referred to herein as p ropylene glycol is specifically the α

- propylene glycol (1,2 diol) isomer in which the two hydroxy (diol) moieties are adjacent, or 1,2. The less common congeneric 1,3

- diol isomer, called β

- pro pylene glycol, is a different compound.

Chemical Structure of Propylene Glycol



## CH 3



## HO

— CH

— CH 2 

## — OHPage 5 of 14 Based on information provided in the US EPA RED (2006), the UNEP SIDs (2001), and

EPISuite TM 4.0 modeling, the following summary of the physicochemical data for propylene glycol are relevant to consider in the assessment of environmental and mammalian safety.

Non

- volatile viscous liquid; estimated vapor pressure 0.11mm Hg at 25°C; Boiling Point,

155.2 o C at 760 mm Hg; Specific Gr avity, 1.040 mg/ml at 20 o C

Polar/non

- lipophilic unlikely to bioaccumulate: log K

ow - 0.78

Solubility: Miscible in water; solubility estimated at 8.11 e+005 (mg/L) at 25 o C; soluble

in acetone and chloroform.

Log K
oc (K

ow method) of

- 0.407 indicates a low potential to bind to soil.

EPISuite 4.0 Estimated Atmospheric Oxidation indicates potentially rapid oxidation and degradation in air, Half

- Life 10.12 hours.

Low potential to bioaccumulate. Log BCF = 0.5

Not persistent in the environment. EPI Suit eTM 4.0 Primary Level Three Fugacity Model indicated a preference for the water (34.5%; half

- life 208 hours) and soil compartments (65%; 416 hours half

- life).

Common Name: Propylene glycol

CAS Chemical Name: 1, 2

- Propanediol CAS Reg Number: 57

- 55

- 6

OPP Chem Code: 868603 Synonyms: 2,3

- Propanediol: 1, 2

- Dihydroxypropane; Methylethylene Glycol; Trimethyl Glycol; 1,2

- Propylene Glycol; Monopropylene Glycol; Propane

- 1, 2

- diol; α

– Propylene Glycol; Propanediol; 1,2

- Dihydroxypropane; 2

- Hydroxypropanol; Methyethyl Glycol; Methyl Glycol

Commercial Na mes : Dowfrost; GR12; Sirlene; Solar Winter Ban

Chemical Formula: C 3 H 8 O 2 Molecular Weight: 76.00 g/mol

IV. CURRENT USE

Due to its low toxicity, p ropylene glycol is widely used as an inert ingredient in agrochemical, industrial chemical, pharmaceut ical, food, and personal care formulations. The intended purposes include that of a solvent, emulsifier, humectant, wetting agent, de

- icer, antifreeze, fragrance carrying agent, and sanitizer.Page 6 of 14 Propylene glycol is already exempt from the requirement of a tolerance when used as a diluent (solvent, cosolvent) in pesticide formulations as described below:

40 CFR §180.910. Propylene glycol is exempt from the requirement of a tolerance when used as a diluent (solvent, cosolvent) in accordance with good agr icultural practice as an inert ingredient in pesticide formulations when applied to growing crops or to raw agricultural commodities after harvest. This includes use in food and feed handling establishments for products other than

antimicrobials.

40 CFR §180.930. Propylene glycol is exempt from the requirement of a tolerance when used as a defoaming agent (solvent, cosolvent) in accordance with good agricultural practice as an inert ingredient in pesticide formulations applied to animals.

FDA has also ap proved propylene glycol as a preservative in food products as listed in 21 CFR,

Part 184

- Direct Food Substances Affirmed as Generally Recognized as Safe (GRAS):

184.1666(d). The ingredient is used in foods at levels not to exceed current good manufacturin g practice in accordance with Sec. 184.1(b)(1) which includes the following:

Current good manufacturing practice results in maximum levels, as served, of:

− 5 percent for alcoholic beverages, as defined in Sec. 170.3(n)(2) of this chapter;

− 24 percent for con fections and frostings as defined in Sec. 170.3(n)(9) of this chapter;

− 2.5 percent for frozen dairy products as defined in Sec. 170.3(n)(20) of this chapter;

− 97 percent for seasonings and flavorings as defined in Sec. 170.3(n)(26) of this chapter;

− 5 perce nt for nuts and nut products as defined in Sec. 170.3(n)(32) of this chapter; and

- 2 percent for all other food.

V. TOXICOLOGICAL PROFILE

Propylene glycol has an extensive database of acute oral toxicity in the rat, mouse, rabbit and Guinea pig; a cute eye irritation in the rabbit, acute skin irritation in the rabbit, subchronic, chronic, developmental, and reproductive toxicity, carcinogenicity, mutagenicity,

m etabolism/pharmacokinetics and dermal toxicity studies. These data have been summarized in the UNEP SIDs (2001) and EPA RED (2006) reports. The Antimicrobials Division Toxicology Endpoint Selection Committee (ADTC) memorandum and the toxicology chapter are available in EPA’s Pesticide Docket, EPA

- HQ

- OPP

- 2006

- 0831 at www.regulations.gov . The remainder of the toxicological profile is taken directly from the Agency’s 2006 RED document.

A. Hazard AssessmentPage 7 of 14 EPA (2006) concluded that there are no toxicity endpoints of concern for oral, dermal, or

inhalation exposure to propylene glycol. This conclusion is based on the results of toxicity testing of propylene glycol at dose levels near or above testing limits (as established in the OPPTS 870 series harmonized test guidelines).

1. Acute Toxicity

EPA concluded that no significant acute toxicity was observed. There were no endpoints of concern for oral, dermal, or inhalation exposure to propylene glycol.

Table 1. Acute Toxicity of Propylene Glycol

Guideline Study Type Results (mg/kg) Toxicity Category

870. 1100 Acute Oral

- Rat LD 50 range = 8,000

– 46,000 IV

870.1100 Acute Oral

- Mouse LD 50 range = 23,000

– 24,900 IV

870.1100 Acute Oral

- Rabbit, Guinea pig LD 50 range = 18,000

– 20,000 IV

870.2400 Acute Eye Irritation

- Rabbit Non

- irritant IV

870.2500 Acute Skin Irritation

- Rabbit Non

- irritant IV

870.2600 Skin Sensitization Non

- sensitizer NA

2. Repeat Dose Dermal Toxicity and Carcinogenicity Study

Mice

In 1973, Stenback and Shubik conducted a 12 week, repeat dose, dermal toxicity study on female Swiss mice from the Eppley colony. Seven compounds were evaluated, propylene glycol was one of the compounds tested. The results for propylene glycol are reported here.

Seven week old female Swiss mice from the Eppley colony were used. Animals were randomized and littermates were separated. There were 50 animals per concentration group. Propylene glycol was tested at 100 %, 50 % and 10 % (~500,000, 100,000, 50,000, mg/kg bw/day) concentration. Animals were housed in plastic cages, 10 per group. Commercial bedding was used and the animals fed a commercial diet. 135 untreated animals served as a control group.

The application consisted of 0.02 ml dropped on the dorsal skin between the flanks, twice a week

on a 1

- inch square area whi ch was shaved regularly. Animals were checked weekly and all lesions as well as tumors were recorded. Animals were allowed to die spontaneously or w ere sacrificed when moribund. Complete autopsies were performed on all animals. The skin from all animal s, all grossly observed tu m ors and other lesions in the lungs, livers kidneys, etc from treated as well as control groups were evaluated histologically.

None of chemicals studied (including propylene glycol) produced a statistically significant

increase i n skin tumor incidence as compared to the controls. The treatments did not produce lesions in other organs related to the treatment. The authors cited a study by Gaunt et al. (1972) did not report any pathological findings or carcinogenic potential after feeding propylene glycol inPage 8 of 14 concentrations up to 50,000 ppm (~2,500 mg/kg bw/day) in rats. Stenback and Shubick state that the findings of Gaunt et al. are similar to what they reported.

Rats

As noted earlier, Gaunt et al. (1972) conducted a long

- te rm toxicity study of propylene glycol in

rats. In the study, groups of 30 male and female weanling rats (strain not specified) were fed diets containing 0, 6

, 250, 12,500, 25,000, or 50,000 ppm (approximately 312.5, 625, 1,250, 2,500 mg/kg bw/day respectiv ely) propylene glycol for 2 years. Animals were observed daily for signs of ill

health or death.

At weeks 13, 21, 52 and 80 of the study, blood was collected from male and female animals from each group that had been fed on diets containing 0 (control), 2 5,000 and 50,000 ppm (~ 1,250 and 2,500 mg/kg bw/day) propylene glycol. All samples were examined for hemoglobin content, packed cel l volume and counts of erythrocytes, total leucocytes and the individual types of leucocytes. Counts of reticulocytes were also conducted on samples obtained after weeks 52, 54 and 80. At week 104, hematological studies were limited to measurements of hemoglobin concentration and stained blood smears from all surviving rats.

At weeks 13, 30 and 52, urinary concentration tests were conducted on selected individual rats from the control group and the two highest dose groups ( 25,000 and 50,000 ppm ; ~1,250 and 2,500 mg/kg bw/day ). Measurements were taken of specific gravity and volume of urine produced during a 6 hr period o f water deprivation, during a 2

- hour period of water load of 25 ml/kg and during a 4

- hour period commencing 16

- hr after the water load. Urinary cell counts were taken on

the 6

- hr. samples.

After week 104, all surviving animals were sacrificed by exsang uination under barbiturate anesthesia. Autopsies were conducted and any macroscopic abnormalities noted for the brain, heart, liver, spleen, kidneys, adrenals, gonads, stomach, small intestine and caecum. Samples of these organs and of salivary gland, tr achea, aorta, thymus, l y mph nodes, pituitary, urinary bladder, colon, rectum, pancreas, uterus, muscle and any tissue that appeared to be abnormal.

During the long

- term study, a short

- term study was conducted concurrently. Groups of 15 male

and female ra ts (strain not specified) of similar age and body weight to those in the long

- term study were used. Concurrent with the long

- term study these rats were fed diets containing 0 (control) and 50,000 ppm (2,500 mg/kg bw/day) propylene glycol for 15 weeks. Bo dy weights and food consumption were not recorded as the dietary level was the same as for the long

- term study. During the last week of the study, renal concentration tests were conducted as described earlier. Additionally, the activity of glutamic

- oxala cetic transaminase was estimated I the 6

- hr urine samples. Blo o d was collected from the aorta at autopsy and hematological examinations were conducted as described above. Serum was separated and measurements were made of urea

concentration and of the act ivities of glutamic

- oxalacetic and g l utamic

- pyruvic transaminases. The brain, heart, liver, spleen, kidneys, adrenals, gonads and pituitary were weighted at autopsy.

The results were: At over two times the limit dose (1,000 mg/kg bw/day) n o abnormalit ies were seen in the appearance or behavior of the rats. There were no statistically significant differencesPage 9 of 14 between treated and control rats in cumulative death rates, body weight gain or food consumption. The mean daily intakes of propylene glycol were approximately 0

- 2, 0

- 45, 0

- 9 and 1

- 7 g/kg for

males and 0

- 3, 0

- 5, 1

- 0 and 2

- 1 g/kg in females at the four dietary levels. There were no significant differences between treated and control rats in the results of hematological studies or in the urinary cel l excretion or renal concentration tests. Values of absolute organ weights and weights or organs relative to the terminal body weight were similar in all treated and control

groups.

In the shor t

- term study there were no differences between the controls group and those fed a diet containing 50,000 ppm (2,500 mg/kg bw/day) propylene glycol in the analyses of serum and urine, hematological indices or organ weighs. Nor abnormalities were seen at autopsy.

There were no statistically significant differences between the control animals (0 ppm) and the test animals (do s es up to and including 50,000 ppm (2,500 mg/kg bw/day) . There was no evidence of any dose

- related effects. Thus no carcinogenic potential has been detected with dietary levels up

to an includi ng 50,000 ppm (2,500 mg/kg bw/day) propylene glycol administered over most of the

life

- span of rats. The no observed adverse effect level is considered to be 50,000 ppm (2,500mg/kg bw/day) in these two studies.

Dogs

In an oral toxicity study by Weil e t al. (1971) beagle dogs were fed 0, 2,000 or 5,000 mg/kg bw/day propylene glycol for 2

- years. No treatment related effects were observed

EPA c oncluded that propylene glycol was negative for carcinogenicity in studies conducted up to the testing limit do ses established by the Agency; therefore no further carcinogenic analysis was required. The Antimicrobial Division’s Toxicology Committee stated that public literature sources which examined the carcinogenic potential of propylene glycol have shown that i t is negative for carcinogenicity.

Immunotoxicity and neurotoxicity studies were not available in the database. However, there was no evidence of immunotoxicity or neurotoxicity in the studies that were submitted.

3. Mutagenicity Potential

EPA con cluded that propylene glycol was not mutagenic or genotoxic on the basis of a battery of studies that included the bacterial gene mutation assay using Salmonella typhimurium (AMES) in vitro assay

, in vitro Chinese hamster ovary (CHO) mutation assay, Chines e hamster ovary (CHO) chromosomal aberration assays, and an in vitro sister chromatid exchange assay.

4. Reproductive and Developmental Toxicity

Kavlock, Short and Chernoff (1987) conducted an In Vivo teratology screening study. Propylene glycol was one of the compounds evaluated. Sixty

- day old time pregnant female CD

- 1 mice from Charles River Laboratory were used in the study. Propylene glycol was administered by oral gavage at a dose rate of 10,000 mg/kg bw/day. Administration was for 5 days . Pr egnant females were then dosed on day 8

- 12 of gestation. Compared to the control group which was administeredPage 10 of 14 0 mg/kg bw/day propylene glycol, there were essentially no differences in maternal effects of

neonatal effects. Those data were from treatment l evels 10 times higher than the limit dose of 1,000 mg/kg bw/day.

The National Toxicology Program (NTP) conducted a continuous breeding study on COBScrl:CD

1(ICR)BR outbred albino mice. Mice were exposed to 0, 1, 2.5 or 5 % (approximately 1,820, 4,800, 1 0,100 mg/kg bw/day) propylene glycol in the drinking water for 18 weeks. Maternal, offspring and reproductive toxicity were not observed (MRID46892207).

Moreover as already noted, UNEP (2001) concluded that propylene glycol is not a reproductive or

devel opmental toxicant with NOELs in rats, mice, rabbits, or hamsters ranging from 1.2 to 1.6 g/kg bw/day (all four species). These doses vastly exceed the expected propylene glycol exposure associated with the already approved pesticide ingredient approvals u nder 40 CFR §180.910 and 40 CFR §180.930 uses, and the intended 40 CFR §180.910(a) use in antimicrobial formulations.

5. Metabolism

The World Health Organization (WHO, 2001) has summarized the metabolism of propylene glycol

in mammals. Propylene gly col should be readily metabolized to lactic acid at the typical low

- level exposures associated with the already approved pesticide inert ingredient registrations under 40 CFR §180.910 and 40 CFR §180.930 uses, and the intended 40 CFR §180.940(a) use in

ant imicrobial formulations. At higher concentrations (absorbed doses), propylene glycol is primarily excreted unchanged in the urine.

• “In studies of the minor pathways of metabolism of propylene glycol, administration to rats in drinking

- water resulted in e xcretion unchanged in the urine ...Propylene glycol given orally to rabbits was conjugated with glucuronic acid and excreted in the urine...”

Propylene glycol is oxidized to lactic acid via two biochemical pathways. If phosphorylated, propylene glycol is con verted to acetol phosphate, lactaldehyde phosphate, lactyl phosphate, and

then lactic acid. If propylene glycol is not phosphorylated, it is successively oxidized to lactaldehyde, methylgloyoxal, and lactic acid. In both cases, lactate is subsequently co nverted to pyruvate, which enters the citric acid cycle and/or the gluconeogenesis pathway.

D. Toxicity Endpoint Selection

The available toxicity studies indicate that propylene glycol exhibits very low toxicity over

- all.

The No Observed Adverse Effec t Levels (NOAELs) were > 2, 5 0 0 mg/kg bw/day (above the limit dose of 1,000 mg/kg bw/day). Since signs of toxicity were not observed, a toxicological endpoint of concern for use in risk assessment, was not identified. Therefore, a quantitative risk assess ment for propylene glycol is not necessary.

VI. Special Consideration for Infants and Children and Rationale that the FQPA Safety Factor is not Required

The FQPA Safety Factor (as required by the Food Quality Protection Act of 1996) is intended to

prov ide an additional 10

- fold safety factor (10X), to protect for special sensitivity in infants andPage 11 of 14 children to specific pesticide residues in food, drinking water, or residential exposures, or to compensate for an incomplete database. EPA concluded there ar e no toxicity endpoints of concern for oral, dermal, or inhalation exposure to propylene glycol based on the low toxicity observed in studies conducted near or above testing limit doses as established in the OPPTS 870 series harmonized test guidelines. Th is decision is supported by the lack of genotoxic, reproductive, and developmental toxicity reported by UNEP (2001). Therefore, EPA has removed the FQPA Safety Factor (i.e., reduced to 1X) for propylene glycol, because there is no pre

- or post

- natal evide nce for increased susceptibility following exposure.

VII. Exposure Assessment

On the basis of the data summarized earlier, no acute or chronic toxicity endpoints were proposed by EPA for an acute or chronic risk assessment and therefore no acute or c hronic dietary exposure

assessments are warranted.

VIII. Aggregate Exposure and Risk

1. Potential Dietary and Residential Exposures

EPA stated in the 2006 RED: Dietary exposure (food and drinking water) could potentially occur from the use of propylene gl ycol as a food additive, from food packaging, and from its use as an inert ingredient in pesticide formulations. Residential exposure could also potentially occur as a result of the use of propylene glycol in and around the home as a sanitizer, disinfectan t and pet treatment. However, risk estimates have not been calculated by EPA for potential exposures to propylene glycol on food, in drinking water, or as a result of use in residential settings because there are no toxicological endpoints of concern acco rding to a review of the available toxicity data.

Since the 2006 RED, no new data have been submitted to alter the conclusions about the toxicity of propylene glycol. The Agency still has not identified an endpoint for risk assessment purposes;

therefor e, the exposure assessment for this action is qualitative, much like the assessment done in the 2006 RED. This action may result in additional exposures to the propylene glycol from its use on food contact surfaces and on dairy or other food

- processing eq uipment and utensils.

2. Aggregate Exposure

EPA stated in the 2006 RED: The Food Quality Protection Act amendments to the Federal Food, Drug, and Cosmetic Act (FFDCA, Section 408(b)(2)(A)(ii)) require “that there is a reasonable certainty that no harm wi ll result from aggregate exposure to pesticide chemical residue, including all anticipated dietary exposures and other exposures for which there are reliable information.” Aggregate exposure will typically include exposures from food, drinking water, resid ential uses of a pesticide and other non

occupational sources of exposure. Since toxicological endpoints for risk assessment were not identified based on the available data, an aggregate risk assessment was not conducted by EPA for propylene glycol.Page 12 of 14 Simila rly, for this action, EPA did not conduct a quantitative aggregate risk assessment since hazard endpoints were not identified.

IX. Occupational Exposure/Risk Pathway The Agency believes that amending the existing tolerance exemption to include 40 CFR § 180.940(a) will not significantly/measurably increase occupational exposure. The change in use pattern would be expanded to include food contact surfaces such as tableware, utensils, dairies and beverage and food processing plants. In view of the regulat ory history of propylene glycol, i.e., approved use under 40 CFR §180.910 and §180.930 and no new toxicological information to indicated otherwise, it is not necessary to quantitatively assess occupational exposure.

X. CUMULATIVE EFFECTS

Section 408 (b)(2)(D)(9v) of 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 pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not conducted a common mechanism of toxicity evaluation for propylene glycol.

JECFA (2001) has repo rted that propylene glycol does not produce a toxic metabolite. Thus, the Agency has assumed that propylene glycol does not have a common mechanism of toxicity with other substances. As a result, any potential human health risks would be those that resul t only from the use of propylene glycol as a pesticide active ingredient (bacteriostat and fungistat) and as an inert ingredient in food use and non

- food use pesticide formulations.

XI. ENVIRONMENTAL RISK

UNEP (2001) has summarized propylene glycol’ s environmental fate characteristics and its toxicity to aquatic organisms:

• Propylene glycol is not volatile and it is miscible with water.

• The concentrations of propylene glycol in the atmosphere are expected to be extremely low because of its low vapor pressure and high water solubility.

• Propylene glycol is readily biodegraded in water or soil. Four studies reported >60% biodegradation in water in 10 days.

• Propylene glycol is not expected to bioaccumulate. The calculated BCF is <1.

• Propylene glycol is not acutely toxic to aquatic organisms except at very high concentrations that would exceed the intended use as a pesticide inert ingredient according to the current 40 CFR §180.910 and §180.930 uses and the proposed 40 CFR §180.940(a) applications . The

m easured freshwater aquatic toxicity data of propylene glycol to fish, daphnia, and algae, have

LC/EC 50 ’s that exceed values of >18,000 mg/l (18,000 ppm). Additionally, using an

assessment factor of 100 and the Ceriodaphnia data (48

- hour EC 50 = 18,340 mg/l ), the PNEC is 183 mg/l.Page 13 of 14 XII. ENVIRONMENTAL JUSTICE

Potential areas of environmental justice concerns, to the extent possible, were considered in the 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, HED and RD estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food

and water co nsumption 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 the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pes ticide 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, the OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate,

non

- dieta ry based on home use of pesticide products and associated risks for adult applicators and for toddlers, youth s, and adults entering or playing on treated areas post

- application are evaluated. Further considerations are currently under development as OPP has committed resources and expertise to the development of specialized software and models that consider expo sure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

XI I I

. CONCLUSIONS

In 2006, based on the available data, EPA concluded that propylene glycol exhibits low toxicity and that exposure to p ropylene glycol used both as a pesticide active ingredient and/or as a pesticide formulation inert ingredient does not present risks of concern. JECFA has also reported that propylene glycol is either readily excreted unchanged or not metabolized to toxic metabolites. FDA has also categorized propylene glycol as generally recognized as safe and approved its use in all food categories, ranging from 2% to 97% in a variety of foods.

Furthermore, in determining whether or not infants and children are parti cularly susceptible to toxic effects from propylene glycol residues, EPA has considered the completeness of the database for developmental and reproductive effects. The FQPA Safety Factor has been removed (i.e., reduced to 1X) because there is no pre

- or post

- natal evidence for increased susceptibility following exposure.

Based on the information presented above and upon the information in the EPA Reregistration Eligibility Decision For Propylene Glycol and Dipropylene Glycol (2006), the Agency approves o f the use of Propylene Glycol without limitation as an inert ingredient in antimicrobial pesticide formulations applied to “food contact surfaces in public eating places, dairy processing equipment, and food processing equipment and utensils” as described in 40 CFR § 180.940(a).Page 14 of 14 REFERENCES

Gaunt, I., F. Carpanini, P. Grasso and A. Lansown. 19 72. Long

- term Toxicity of Prop ylene Glycol in Rats. Food Cosmet. Toxicol. 10: 151

- 162.

JECFA. Propylene Glycol. 2002. Joint FAO/WHO Expert Committee on Food Additives www.inchem.org/documents/ jecfa /jeceval/jec_2031.htm

.

Kavlock, R., R. Short Jr. and N. Chernoff. 1987. Further Evaluation of an In Vivo Teratology Screen. Teratogenesis, Carcinogenesis and Mutagenesis. 7: 7

- 16.

National Toxicology Program. 2003. Center for the Evaluation of Risks to Human Reproduction.

NTP

- CERHRExpert Panel Report on the Reproductive and Developmental Toxicity of Propylene Glycol. (MRID 46892207).

Stenback, F. and P. Shubik. 1974. Lack of Toxicity and Carcinogenicity of Some Commonly Used Cutaneous Agents. Toxicol. and Applied Pharmacol. 30: 7

- 13.

UNEP SIDS, 2001, Initial Assessment Report for the 11 th SIAM, 1,2

- Dihyroxypropane (CAS 57

- 55

- 6), www.chem. unep .ch/irptc/sids/oecdsids/57

- 55

- 6.pdf

. United Nations Environment Programme Screening Information Dataset.

US EPA Registration Eligibility Document for Propylene Glycol and D ipropylene Glycol dated September 2006 (available in EPA Docket, EPA

- HQ

- OPP

- 2006

- 0831).

Weil, C., M. Woodside, H. Smyth Jr. and C. Carpenter. 1971. Results of feeding propylene glycol in the diet to dogs for two years. Food Cosmet. Toxicol. 9: 479.

World Health Organization (WHO) Food Additives Series: 48 Safety Evaluation Of Certain Food Additives And Contaminants, 2001. Aliphatic Acyclic Diols, Triols, and Related

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