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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

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

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In 

cases where the outline element does not apply, please insert “NA-Remove” and 

maintain the outline. Please do not change the margins, font, or format in your 

pesticide petition. Simply replace the instructions that appear in green, i.e., “[insert 

company name],” with the information specific to your action.

TEMPLATE:

Lyondell Chemical Company

[1E7946]

EPA has received a pesticide petition (1E7946) from Lyondell Chemical 

Company, 1221 McKinney Street, Houston, Texas 77010 requesting, pursuant to section 

408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to 

expand the exemption from tolerance for uses of 2-methyl-1,3-propanediol (CASRN 

2163-42-0) to include uses in food contact surface sanitizing solutions, 40 CFR § 

180.940(a), in addition to existing uses on raw agricultural commodities and animals. 

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

set forth in section 408 (d)(2) of FFDCA; however, EPA has not fully evaluated the 

sufficiency of the submitted data at this time or whether the data supports granting of the 

petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. [NA-Remove]

2. Analytical method. [NA-Remove]

3. Magnitude of residues. [NA-Remove]

B. Toxicological Profile

1. Acute toxicity. 

Acute Oral Toxicity in Rats/LD50 in Rats: Five healthy male and five healthy female 

Albino rats were dosed orally with 2-Methyl-1,3-propanediol at 5.0 g/kg of body weight. 

All animals survived the 5.0 g/kg oral dose in generally good health. Body weight 

increases were normal. Necropsy results were normal in 8/10 animals. The LD50 was 
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determined to be greater than 5.0 g/kg of body weight.

Acute Dermal Toxicity in Rabbits/LD50 in Rabbits: Five healthy male and five healthy 

nulliparous and non-pregnant female New Zealand Albino rabbits were dosed dermally 

with 2-Methyl-1,3-propanediol at 2.0 g/kg of body weight. The test article was kept in 

contact with the intact skin for 24 hours. Nine of ten animals survived the 2.0 g/kg 

dermal application. One female died on day 12 with no abnormal predeath physical signs. 

The death did not appear to be related to the effect of the test article, as the animal 

appeared normal for 11 days. Body weight changes were normal in 7/9 survivors. Two 

animals lost weight during the study. Dermal reactions, were absent to slight on day 1, 

and absent on days 7 and 14. Necropsy results of survivors were normal in 4/9 animals. 

The LD50 was calculated to be greater than 2.0 g/kg of body weight. 

Primary Dermal Irritation in Rabbits: Six healthy New Zealand Albino rabbits were 

dosed dermally with 2-Methyl-1,3-propanediol. 0.5 mL of the test article was applied to 

two intact and two abraded sites/rabbit for a total dose of 2.0 ml/rabbit. The test article 

was kept in contact with the skin for 4 hours. There was no erythema or edema noted 

during the observation period.

Eye Irritation in Rabbits: Nine healthy New Zealand albino rabbits, free from evidence of 

ocular irritation or corneal damage, as determined by pretest fluorescein dye procedures, 

were dosed with 2-Methyl-1,3-propanediol. 0.1 mL of the test article was placed into the 

conjunctival sac of one eye of each rabbit. Six eyes remained unwashed. Three eyes 

were washed 20-30 seconds after dosing for one minute with lukewarm water. 

UNWASHED: All six eyes appeared normal during the study. WASHED: There was no 

corneal opacity or iritis. Slight conjunctival irritation, noted in 1/3 eyes, cleared by day 

2. Two eyes appeared normal during the study.

Acute (4-hour) Inhalation Toxicity Study in Rats: One group of five male and five female 

rats were exposed by nose-only to a test atmosphere containing the limit concentration of 

5.1 ± 0.2 g 2-Methyl-1,3-propanediol per m3 for a 4-hour period. The Mass Median 

Aerodynamic Diameter (MMAD) of the particles in the aerosol was 2.4 @m with a mean 

geometric standard deviation of 1.4. Except for a slightly decreased breathing rate in the 

fourth hour of exposure in one female animal, no exposure-related abnormalities were 

seen during or shortly after exposure or during the 14-day observation period and no 

mortality occurred. For rats of this strain and age, mean body weight gain was 

considered to be within the normal range. Findings at necropsy were limited to the lungs. 

Thickened hyalin spots or small areas were seen on all lobes of the lungs in all female 

and in three male animals. In a fourth male animal small white areas were seen on all 

lobes of the lungs. It was concluded that the 4-hour LC50 value of 2-Methyl-1,3-

propanediol is higher than 5.1 g/m3 for both sexes.

Assessment of Contact Hypersensitivity in the Albino Guinea Pig (Maximization Test:

Guinea pigs received intradermal and epidermal exposures of 2-Methyl-1,3-propanediol. 

In the main study, the experimental animals were intradermally injected with a 10% 

concentration and epidermally exposed to undiluted test substance, while the control 
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animals were similarly treated, but with the vehicle only and with a dry patch. Two 

weeks after the epidermal application all animals were challenged with test substance 

concentrations of 100%, 50% and 25%, and the vehicle (distilled water). The epidermal 

exposure of 2-Methyl-1,3-propanediol in the induction phase resulted in no skin 

irritation. The epidermal exposure of 2-Methyl-1,3-propanediol in the challenge phase 

resulted in three positive sensitization reactions in response to the 50% test substance 

concentration. Under the conditions used in this study, 2-Methyl-1,3-propanediol 

resulted in a sensitization rate of 15 per cent, and is considered to have mild sensitizing 

properties.

2. Genotoxicty.

Evaluation of the Mutagenic Activity In An In Vitro Mammalian Cell Gene Mutation Test 

with V79 (Chinese Hamster Cells (with independent repeat): 2-Methyl-1,3-propanediol 

was tested in an in vitro mammalian cell gene mutation test with V79 Chinese hamster 

cells in the presence and absence of a metabolic activation system (S9-mix). 2-Methyl1,3-propanediol was tested up to and including a concentration of 5000 ug/ml in the 

absence and presence of S9-mix. It did not induce a significant, dose-related increase in 

the mutant frequency at the HPRT-locus in two independently repeated experiments with 

or without metabolic activation. The positive control chemicals ethylmethanesulphonate 

(6 mM) and dimethylnitrosamine (8mM) produced 14 to 23-fold and 8 to 10-fold 

increases respectively in the mutant frequency, demonstrating the sensitivity of the assay 

and the activity of the S9-mix. It was concluded that 2-Methyl-1,3-propanediol is not 

mutagenic in the V79/HPRT gene mutation test system, as described in this report.

Evaluation of the Ability to Induce Chromosome Aberrations in Cultured Peripheral 

Human Lymphocytes (with independent repeat): 2-Methyl-1,3-propanediol was examined 

for the induction of chromosome aberrations in cultured peripheral human lymphocytes 

in the presence and absence of a metabolic activation system (Aroclor-1254 induced rat 

liver S9-mix) at test levels up to 5000 ug/ml. The first experiment used a 24 h and 48 h 

fixation period, and the second experiment a 24 h fixation period. None of the tested 

concentrations induced a statistically and biologically significant increase in the number 

of cells with chromosome aberrations, with or without S9-mix. Positive control 

chemicals, mitomycin C and cyclophosphamide, both produced a statistically significant 

increase in the incidence of cells with chromosome aberrations, validating the optimal 

test conditions and metabolic activation system (S9-mix). It is concluded that 2-Methyl1,3-propanediol is not clastogenic in human lymphocytes under the experimental 

conditions described.

Evaluation of the Mutagenic Activity of in the Ames Salmonella/Microsome Test (with 

independent repeat): 2-Methyl-1,3-propanediol was tested in the Ames 

Salmonella/microsome plate test up to and including a concentration of 5000 @g/plate in 

the absence and presence of S9-mix. The test substance did not induce a dose-related 

increase in the number of reverent (His+) colonies in each of the four tester strains 

(TA1535; TA1537; TA98 and TA100). The results were confirmed in an independently 

repeated experiment. The test substance was not considered mutagenic in this test system.
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3. Reproductive and developmental toxicity.

Embryotoxicity and Teratogenicity Study Administered by Oral Gavage in Wistar Rats:

Timed pregnant female Wistar rats were administered 2-Methyl-1,3-propanediol at 

dosage levels of 300, 600 or 1000 mg/kg body weight by oral gavage daily on gestation 

days 0 to 20. Control group females received daily oral administration of water (MilliU). On day 21 of gestation, all females were euthanized. Oral dosing of pregnant female 

Wistar rats with 2-Methyl-1,3-propanediol, at dose levels of 300, 600 or 1000 mg/kg 

body weight/day during days 0 to 20 of gestation inclusive, revealed no maternal toxicity.

Treatment at 600 and 1000 mg/kg body weight/day was associated with a slight increase 

in embryonic resorptions and a corresponding slight decrease in live litter size, compared 

with the concurrent controls. However, as all values remained within the laboratory 

background control ranges, the findings were considered to be of doubtful toxicological 

significance. There was no indication of an adverse effect of 2-Methyl-1,3-propanediol 

on morphological development or skeletal ossification in utero. In The No Observed 

Effect Level (NOEL) was 300 mg/kg body weight/day.

In order to clarify the findings of the NOTOX study, subsequent expert review of the 

study and conduct of a second rat developmental toxicity study were performed. In the 

independent review, a reproductive and developmental expert, L. Irvine (TAS-Environ) 

compared the rate of embryonic resorptions with additional recent test and historical data 

for the same rat strain and supplier. The review revealed the following:

- By comparison with the additional data, it was obvious that the incidence of 

embryonic deaths in the control group in the 2-Methyl-1,3-propanediol study was 

unusually low, while the values for the treated groups were typical for the strain.

- Statistically significant inter-group differences in resorptions would not be 

expected with a more representative control group.

- With no other indications of embryotoxicity and no dose-related difference in 

mean live litter sizes, findings of toxicological significance are highly unlikely.

The second rat embryotoxicity and teratogenicity study also confirmed the results of the 

first study.

An Oral (Gavage) Prenatal Developmental Toxicity Study in Rabbits: 2-Methyl-1,3-

propanediol in the test vehicle, deionized water, was administered to three groups of 25 

bred New Zealand white rabbits once daily from gestation days 0 through 28. Dosage 

levels were 250, 500 or 1000 mg/kg/day administered at a dose volume of 0.25, 0.50, or 

1.0 ml/kg, respectively. A concurrent control group composed of 25 bred females 

received the vehicle, deionized water, on a comparable regimen at 1.0 ml/kg. The route 

of administration was oral by gastric intubation. On gestation day 29, a 

laparohysterectomy was performed on all animals. One and two females in the 500 and 

1000 mg/kg/day groups, respectively, died during the study, probably due to intubation 

trauma or aspiration; no relationship to test article administration was evident. There 

were no test article-related maternal clinical observations or effects on mean body 

weights, body weight gains, net body weights, net body weight gains, gravid uterine 

weights or food consumption at any dose level. There were no test article-related internal 
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findings noted at the scheduled necropsy. Intrauterine growth and survival were 

unaffected in the 250, 500 and 1000 mg/kg/day groups. No test article-related fetal 

malformations or developmental variations were noted in any fetuses in this study. Based 

on the results of this study, a dose level of 1000 mg/kg/day was considered to be the noobserved-adverse-effect level (NOAEL) for maternal and developmental toxicity when 2-

Methyl-1,3-propanediol was administered orally to rabbits.

An Oral (Gavage) Two-Generation Reproductive Toxicity Study in Rats:

The study was conducted to evaluate the potential adverse effects of 2-Methyl-1,3-

propanediol administration on the reproductive capabilities of the F0 and F1 generations 

and on F1 and F2 neonatal survival, growth, and development. The test article was 

administered by gavage once daily for at least 70 consecutive days prior to mating to 

three groups of F0 and F1 parental Crl:CD®(SD)IGS BR rats (30/sex/group). A control 

group of identical design received deionized water on a comparable regimen. Test article 

administration continued throughout mating, gestation and lactation, until euthanasia for 

F0 and F1 parental animals. 

All F0 and F1 females were allowed to deliver and rear their pups until weaning on 

lactation day 21. On that day, 35 pups/sex/group from the pairing of the F0 animals 

(including five extra animals/sex/group) were selected for use in the F1 generation. 

These animals were dosed from postnatal day (PND) 22-27, inclusively. On PND 28, 30 

offspring/sex/group were selected to constitute the F1 generation. All surviving F0 and 

F1 parental animals received a complete detailed gross necropsy following the 

completion of weaning of the F0 and F1 pups; selected organs were weighed. Designated 

tissues from 10 F0 and F1 parental animals/sex/group in the control and in the 1000 

mg/kg/day groups were examined microscopically. No test article-related mortalities or 

clinical findings were observed in the F0 or F1 generation. All F1 animals that were 

paired survived to the scheduled necropsy.

Reproductive parameters were not adversely affected by test article administration at 

dose levels of 100, 300 and 1000 mg/kg/day during the F0 or F1 generations. No adverse 

test article-related effects on weekly gestation or lactation body weight, body weight 

gain, food consumption or food efficiency were observed in the F0 or F1 generations. 

No test article-related macroscopic or microscopic internal findings were observed in the 

F0 or F1 generation males or females. Absolute and relative (to final body weight) organ 

weights were unaffected by test article administration for males and females in the F0 or 

F1 generations.

Mean F0 or F1 pup body weights, sex ratios, live litter sizes, numbers of dead pups on 

lactation day 0 and viability indices were unaffected by test article administration. No 

test article-related effects on physical development or behavioral responses were 

observed for the F1 pups. No test article-related internal findings were noted in the F0 or 

F1 pups at necropsy. Findings for selected weanling pups did not suggest any effects of 

test article administration.

In conclusion, no parental, neonatal or reproductive toxicity was observed as a 
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result of test article administration at dose levels of 100, 300 and 1000 mg/kg/day. Based 

on the results of this study, the no-observed-adverse-effect level (NOAEL) for parental, 

neonatal and reproductive toxicity was considered to be 1000 mg/kg/day.

4. Subchronic toxicity.

Subacute 14-Day Oral Toxicity by Daily Gavage in the Rat: In this subacute 14-day 

toxicity study, 2-Methyl-1,3-propanediol was administered daily by gavage to SPF-bred 

Wistar rats at 300, 600 or 1000 mg/kg/day, in order to provide a basis for selection of 

dose levels for a 90-day study. There were no treatment-related changes for any of the 

treatment groups for the parameters evaluated. From the results a definitive No 

Observed Effect Level (NOEL) of 1000 mg/kg/day was established.

Assessment of 90-Day Oral Toxicity in the Rat: In this sub-chronic 90 day oral toxicity 

study, 2-Methyl-1,3-propanediol was administered daily by gavage to SPF-bred Wistar 

rats. The study consisted of four groups, each comprising 10 males and 10 females, and 

dosed at 0, 300, 600 or 1000 mg/kg/day. There were no treatment-related changes for any 

of the treated groups for the parameters evaluated at the end of treatment (week 13). 

From the results presented in this report, a definitive No Observed Effect Level (NOEL) 

of 1000 mg/kg/day was established.

5. Chronic toxicity. [NA-Remove]

6. Animal metabolism. [NA-Remove]

7. Metabolite toxicology. [NA-Remove]

8. Endocrine disruption. [NA-Remove]

C. Aggregate Exposure

1. Dietary exposure.

The inert ingredient, 2-methyl-1,3-propanediol, will be added to water-soluble food 

contact surface sanitizer solutions as a solvent and/or surfactant at levels of no more than 

4%.

i. Food.

The amount of 2-methyl-1,3-propanediol expected to be present on food-contact surfaces 

and transferred to food as residues is calculated using a model developed by the Food and 

Drug Administration (FDA) for assessing exposures to antimicrobial pesticide 

formulations. (Division of Food Chemistry and Technology, Center for Food Safety and 

Applied Nutrition, Food and Drug Administration, “Sanitizing Solutions: Chemistry 

Guidelines for Food Additive Petitions” (1988).)

For calculation of severe worst-case exposures specific to 2-Methyl-1,3-propanediol, the 
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assessment assumes that 100% of the residue left on hard treated surfaces is captured 

through contact with food, and that 2-Methyl-1,3-propanediol is always used at its upper 

limit of 4% in the formulation, even in very dilute formulations. Assuming an adult 

average weight of 71.8 kg and a 6 year-old child average weight of 22.5 kg (6 years old), 

the highest dietary intakes of 2-Methyl-1,3-propanediol are calculated to be 0.45 

mg/kg/day and 0.13 mg/kg/day respectively for a formulation assumed to contain only 

0.2% by weight antimicrobial active ingredient. (Average adult weight for assessment 

purposes was taken from EPA’s Exposure Factors Handbook, page 175, and EPA’s 

Child-Specific Exposure Factors Handbook.) 

ii. Drinking water. [NA-Remove]

2. Non-dietary exposure. [NA-Remove]

D. Cumulative Effects

2-Methyl-1,3-propanediol has negligible acute and subchronic toxicity and would 

not contribute to cumulative toxicity effects if mixed with other related materials.

E. Safety Determination

1. U.S. population. Even when extreme worst case exposure calculations are used 

in evaluating the safety of 2-Methyl-1,3-propanediol, large Margins of Exposure are 

found for both adults and children exposed through diet. There is more than a reasonable 

certainty that no harm will result from aggregate exposures to 2-Methyl-1,3-propanediol.

2. Infants and children. The worst-case Margins of Exposure calculated for 

children range from 7,572 to values more than 200 times higher. Based on these 

findings, it may be concluded that there is a reasonable certainty that no harm will result 

from aggregate exposure to 2-Methyl-1,3-propanediol residues by infants and children.

F. International Tolerances

[There are no international tolerances (i.e., MRLs) for 2-methyl-1,3-propanediol.

4812-3050-5998, v. 1