2

Table of Contents

EXECUTIVE SUMMARY......................................................................................................... 3

I. BACKGROUND..................................................................................................................... 7

II. INERT INGREDIENT PROFILE........................................................................................... 7

III. HUMAN HEALTH ASSESSMENT................................................................................... 8

A. Summary of Toxicity Data................................................................................................... 8

B. Toxicity Endpoint Selection .............................................................................................. 16

C. Special Considerations for Infants and Children................................................................. 17

IV. EXPOSURE ASSESSMENT................................................................................................. 17

A. Dietary Exposure: .............................................................................................................. 18

i. Acute exposure ................................................................................................................... 19

ii. Chronic exposure............................................................................................................... 19

iii. Cancer exposure ............................................................................................................... 19

B. Residential Exposure ......................................................................................................... 19

V. AGGREGATE RISK AND DETERMINATION OF SAFETY ............................................ 19

A. Acute Dietary Risk ............................................................................................................... 19

B. Chronic Dietary Risk............................................................................................................ 19

C. Aggregate Cancer Risk for U.S. Population......................................................................... 20

D. Short-Term Aggregate Risk ................................................................................................. 20

E. Intermediate-Term Aggregate Risk ...................................................................................... 20

F. Determination of Safety........................................................................................................ 20

VI. OCCUPATIONAL EXPOSURE/RISK PATHWAY........................................................ 20

A. Occupational Handler Risk................................................................................................ 20

B. Occupational Post-Application Risk.................................................................................. 21

VII. CUMULATIVE EXPSOURE ........................................................................................... 21

VIII. ENVIRONMENTAL JUSTICE STATEMENT............................................................ 22

IX. ENVIRONMENTAL FATE CONSIDERATIONS .......................................................... 22

X. ECOTOXICITY .................................................................................................................... 22

XI. RISK CHARACTERIZATION......................................................................................... 23

REFERENCES ............................................................................................................................. 27

APPENDIX................................................................................................................................... 29
3

EXECUTIVE SUMMARY

Dupont Tate & Lyle BioProducts Company. (198 Blair Bend Drive, Loudon, TN 37774) 

submitted a petition (PP 2E8091), requesting an exemption from the requirement of a tolerance 

pursuant to section 408(d)(1) of the Federal Food, Drug, and Cosmetic Act with respect to 1,3-

propanediol (CAS Reg. No. 504-63-2) as an inert ingredient for pre- and post-harvest (40 CFR 

180.910) and antimicrobial food-contact surface sanitizing formulations (40 CFR 40180.940). 

EPA published the Notice of Filing for this petition in the Federal Register on January 16, 2013 

(78 FE 3377). No substantial comments were received in response to this notice. 1,3-Propanediol 

was approved for non-food use in 2011. The majority of the data in this risk assessment decision 

document has been taken from the 2011 non-food use decision document.

The acute oral toxicity of 1,3-propanediol in rodents, expressed as an LD50 ranges from 

10,500 to 15,789 mg/kg bw. No acute dermal toxicity studies for 1,3-propanediol were available 

in the toxicity database. The acute inhalation toxicicty of 1,3-propanediol in rats produced a LC50

was > 5.0 mg/L. Primary eye irritation studies of 1,3-propanediol on rabbits showed minimal 

effects, slight redness of the conjunctivae, and clearing in less than 24 hours. It is considered 

minimally irritating to the eyes of rabbits. Primary skin irritation studies with 1,3-propanediol 

showed slight to mild erythema and edema to rabbits but clearing after 72 hrs. It is considered 

mildly irritating to the skin of rabbits. Dermal sensitization studies on guinea-pigs showed that 

1,3-propanediol is not a sensitizer.

In a 14-day inhalation toxicity study (MRID 48439008) three groups of 10 male Crl:CD 

(SD) IGS BR rats each were exposed by inhalation to either vapor only or a vapor/aerosol 

mixture of 1,3-propanediol in air at concentrations targeted to 60, 600, or 1800 mg/m3 (0.06, 

0.60 or 1.80 mg/L) for 6 hours/day, 4 or 5 days/week for a total of 9 exposures. A procedural 

control group of 10 male rats were exposed simultaneously to air only. The analytically 

determined mean concentrations of 1,3-propanediol in the exposure chambers were 41, 650 and 

1800 mg/m3 (0.041, 0.650, and 1.800 mg/L) over the duration of the study. All rats survived to 

the termination of the study and were sacrificed at the end of the study duration. There were no 

test substance-related clinical signs of toxicity observed during the study. No statistically 

significant body weight differences were observed in any group. There were no compoundrelated adverse effects noted during clinical observations or pathology evaluations. The NOAEL 

for repeated inhalation exposure to 1,3-propanediol in male rats was considered to be 1800 

mg/m3 or 1.8 mg/L (the highest dose tested) and no LOAEL was identified.

In a 90-day oral toxicity study (MRID 48439004), 1,3-propanediol was administered to 

10 Crl:CD®(SD)BR rats/sex/dose by gavage at dosages of 0, 100, 300 or 1000 mg/kg/day. 

Reverse osmosis-treated water was administered to controls. All animals survived to the 

scheduled necropsy. No test article-related changes in the clinical condition of the animals were 

observed. Mean body weights, body weight gains, food consumption, clinical pathology 

parameters (hematology, serum chemistry) and organ weights were unaffected by test article 

administration. No treatment related changes were observed in eyes up on ophthalmoscopic 

examinations at the end of the study. Spermatogenic endpoints were unaffected in all treated 

males. No treatment-related changes were observed at the macroscopic and microscopic 

examinations. Based on the data obtained, the NOAEL for systemic toxicity of 1,3-propanediol 
4

administered orally via gavage to male and female rats for 91 or 92 consecutive days was 1000 

mg/kg/day (the highest dose tested) and no LOAEL was identified.

The mutagenic potential of 1,3-propanediol was evaluated in a bacterial reverse mutation 

test, an in vitro mammalian cell gene mutation test, an in vitro chromosome aberration assay, an 

in vitro mammalian cell chromosome aberration assay and a mammalian erythrocyte 

micronucleus test. These test were all negative except for the in vitro mammalian cell 

chromosome aberration assay which showed under the reported experimental conditions that 1,3-

propanediol reproducibly induced structural chromosomal aberrations in the V79 Chinese 

hamster cell line. However due to negative in vivo mouse micronucleus assay, there are no 

concern for clastogenicity. Based on the results of these studies, 1,3-propanediol is not 

considered to be mutagenic. 

No carcinogenicity studies on 1,3-propanediol were available in the toxicity database, 

however based on the lack of mutagenicity concerns, lack of any systemic toxicity at the limit 

dose and lack of any structural alerts for carcinogenicity in Derek analysis, , there are no 

concerns for carcinogenicity for 1,3-propanediol.

In a developmental toxicity study, 1,3-propanediol was administered to 20 pregnant 

female Sprague-Dawley (Hag: SD) rats/dose by gavage in 0.8% aqueous hydroxypropylmethylcellulose gel (with constant dose volume of 10 mL/kg bw) at dose levels of 0, 250, or 

1000 mg/kg bw/day on gestation days (GDs) 6 through 15. Dams were sacrificed and necropsied 

on GD 20. There were no treatment-related effects on maternal survival, clinical signs, body 

weight, food consumption, or gross pathology. The maternal LOAEL is not identified, and the 

maternal NOAEL is greater than or equal to 1000 mg/kg bw/day (the highest dose tested). There 

were no treatment-related effects on live litter size, fetal deaths, early or late resorptions, or the 

fetal sex ratio. Mean fetal weights, fetal lengths, and placental weights of the treated groups 

were similar to those of controls and there were no significant increases in the litter incidences of 

any individual morphological variation or retardation for either treated group. The 

developmental LOAEL is not identified, and the developmental NOAEL is greater than or equal 

to 1000 mg/kg bw/day (the highest dose tested).

There were no immunotoxicity or neurotoxicity studies on 1,3-propanediol available in 

the toxicity database. However, there was no evidence of clinical signs of neurotoxicity or 

immunotoxicity triggers in the available database up to the limit dose.

The proposed metabolic pathway for 1,3-propanediol follows that for other simple 

alcohols, where alcohol and aldehyde dehydrogenase enzymes sequentially break down this 

substance to aldehydes and acids used in intermediary metabolism. 1,3-propanediol is 

metabolized to 3-hydroxypropionaldehyde, malondialdehyde or 3-hydroxypropionic acid, 

malonic semi-aldehyde, malonic acid, and ultimately, carbon dioxide and water. 

EPA did not use a safety factor analysis for assessing risk because no toxicological 

endpoints have been identified for this chemical. 
5

Acute and chronic dietary risk assessments were not conducted because no endpoints of 

concern following single or multiple exposures were identified in the available studies. 1,3-

Propanediol is not expected to be carcinogenic. Therefore, a cancer dietary exposure assessment 

is not necessary to assess cancer risk.

The term “residential exposure” is used in this document to refer to non-occupational, 

non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, 

and flea and tick control on pets). Due to the absence of a toxicity endpoint for 1,3-propanediol 

in the database, residential exposure is not expected to be of concern. Therefore a quantitative 

residential exposure risk assessment was not performed.

Short-term aggregate exposure takes into account short-term residential exposure plus 

chronic exposure to food and water (considered to be a background exposure level). 1,3-

Propanediol is used as an inert ingredient in pesticide products that are currently registered for 

uses that could result in short-term residential exposure however no adverse effects were 

attributable to chronic exposure to 1,3-propanediol were seen in the toxicity database; therefore, 

a short-term aggregate risk assessment is not required. 

Intermediate-term aggregate exposure takes into account intermediate-term residential 

exposure plus chronic exposure to food and water (considered to be a background exposure 

level). 1,3-Propanediol is used as an inert ingredient in pesticide products that are currently 

registered for uses that could result in intermediate-term residential exposure however no adverse 

effects were attributable to chronic exposure to 1,3-propanediol were seen in the toxicity 

database; therefore, an intermediate-term aggregate risk assessment is not required. 

Due to the absence of dermal and inhalation toxicity, occupational handler and postapplication risks are not of concern. Therefore occupational handler and post-application risk 

assessments were not performed.

Based on a Biodegradability study (Berti 2007), the compound 1,3-propanediol is readily 

biodegradable. Based on physico-chemical properties, 1,3-propanediol is water soluble and will 

partition to the soil. The low Kow (-0.71) suggests that 1,3-propanediol is not expected to absorb 

by sediment or suspended solids. The study showed that 71% of the compound was converted to 

CO2 after 28 days suggesting that the substance was completely mineralized without any major 

metabolites or degradation products. Due to its rate of biodegradation, 1,3-propanediol is not 

expected to be of major environmental fate concern.

Based on 3 acute ecotoxicity studies, 1,3-propanediol is practically non-toxic to 

freshwater invertebrates, freshwater fish and algae. Freshwater invertebrate, Daphnia magna had 

a 24-hr EC50 of 8285 mg/L and a 48-hr EC50 of 7417 mg/L. The freshwater fish, fathead minnow 

had a 96-hr LC50 of 9720 mg/L. Lastly the algae, Scendesmus subspicatus, had a 72-hr EbC50of 

1.6g/L and a 72-hr ErC50 >10 g/L with a NOAEC ≤ 0.5 g/L.

Taking into consideration all available information on 1,3-propanediol, EPA concludes 

that there is a reasonable certainty that no harm to any population subgroup will result from 

aggregate exposure to 1,3-propanediol when considering occupation, dietary exposure and all 
6

other nonoccupational sources of pesticide exposure for which there is reliable information. 

Therefore, the establishment of an exemption from tolerance under 40 CFR 180.910 and 180.940 

for residues of 1,3-propanediol (CAS Reg. No. 504-63-2) when used as a pesticide inert 

ingredient for pre- and post-harvest (40 CFR 180.910) and antimicrobial food-contact surface 

sanitizing formulations (40 CFR 180.940), can be considered assessed as safe under section 

408(q) of the FFDCA. 
7

I. BACKGROUND

Dupont Tate & Lyle BioProducts Company. (198 Blair Bend Drive, Loudon, TN 37774) 

submitted a petition (PP 2E8091), requesting an exemption from the requirement of a tolerance 

pursuant to section 408(d)(1) of the Federal Food, Drug, and Cosmetic Act with respect to 1,3-

propanediol (CAS Reg. No. 504-63-2) as an inert ingredient for pre- and post-harvest (40 CFR 

180.910) and antimicrobial food-contact surface sanitizing formulations (40 CFR 40180.940). 

The majority of the data summarized below will be referenced from the non-food use

decision document for 1,3-propanediol registered as an inert ingredient in pesticide formulations 

as a solvent, co-solvent, diluent, or freeze point depressant. (US EPA 2011)

1,3-propanediol is manufactured through a multi-step fermentation, separation and 

distillation process using a genetically modified non-pathogenic and non-toxigenic strain of 

Escherichia coli K-12. The production begins with fermentation of corn sugar by E. coli. At the 

end of fermentation, the biomass is deactivated at a high temperature and removed. 1,3-

propanediol is separated from the fermentation broth by a three-step process involving ion 

exchange to remove charged impurities, evaporation to remove water, and distillation to remove 

impurities. No solvents are used in the separation process. The final 1,3-propanediol is a 

flammable, colorless and water soluble liquid. 

II. INERT INGREDIENT PROFILE

A. Summary of Uses

1,3-Propanediol is used in many applications but mainly as a monomer for the production 

of polyesters, polyethers and polyurethanes. It is the raw material for the production of 

biodegradable plastics, films, solvents, adhesives, detergents, cosmetics and medicines. 

(Kaur G. et al. 2012)

1,3-Propanediol is also used as a solvent, co-solvent, diluent, or freeze point depressant in 

several types of pesticide formulations, currently used for non-food use purposes. The 

pesticide products may be formulated as a pressurized liquid and aerosol, non-pressurized 

liquid and trigger spray, ready-to-use, mop and bucket dilutable, and towelettes. It is used 

on the following sites: air treatment (eating establishments, hospitals, commercial, 

institutional, household, bathroom, transportation facilities); medical premises and 

equipment (including instrument pre-soak), commercial, institutional and industrial 

premises and equipment; laundry equipment; hard non-porous surface treatments 

(bathrooms facilities); automobiles; air conditioning filters; environmental inanimate hard 

surfaces; garbage containers/storage. 

The proposed use is intended for pesticide formulations such as fungicides, insecticides, 

rodenticides, and herbicides; and, food contact surface sanitizing solutions for public 

eating places, dairy-processing equipment, and food-processing equipment and utensils. 
8

B. Physical Chemical Properties

Some of the physical and chemical characteristics of 1,3-propanediol, along with its 

structure and nomenclature, are found in Table 1.

Table 1. Physical and Chemical Properties of 1,3-Propanediol

Parameter Value Source

Structure

ChemIDplusLite

CAS # 504-63-2 ChemIDplusLite

Molecular Weight (g/mol) 76.09 ChemIDplusLite

Common Names 1,3-Propanediol, Trimethylene 

glycol, Propane-1,3-diol

ChemIDplusLite

Physical State Liquid ChemIDplusLite

Melting Point (°C) -2.67E+01 ChemIDplusLite

Boiling Point (°C) 214.4 ChemIDplusLite

Density (g/cm3 @ 20°C) 1.0597 MSDS

Vapor Pressure (mmHg @ 25°C) 0.0441 ChemIDplusLite

Partition Coefficient (Kow) -1.04E+00 ChemIDplusLite

Water Solubility (mg/L) 1.00E+06 ChemIDplusLite

Henry's Law Constant 1.74E-07 ChemIDplusLite

III. HUMAN HEALTH ASSESSMENT

A. Summary of Toxicity Data 

Acute Oral Toxicity

In an acute oral toxicity study (MRID 48422607), four rats of each sex, were 

administered 1,3-propanediol at a dose level of 10.5 ml/kg (equivalent to 10,500 mg/kg). 

The animals were weighed, fasted overnight and the calculated dose of undiluted 1,3-

propanediol administered by gavage using a ball-point needle fitted to a syringe. After 

dosing, food and water were available ad libitum throughout a nine day observation 

period. The acute oral LD50 value of rats given undiluted 1,3-propanediol was found to be 

approximately 10 ml/kg (10,000 mg/kg) equivalent to 10,500 mg/kg. Apart from 

piloerection seen in animals 24 hours after dosing there were no other signs of toxicity. 

In another acute oral toxicity study (MRID 48422633), young adult albino rats (Wistarderived) were used. 1,3-Porpnaediol was given undiluted by gavage to groups of five 
9

males and five females in single doses of 9.0, 10.8, 13.0, 15.6, or 18.7 ml per kg body 

weight (equivalent to 9000, 10800, 13000, 15600 or 18700 mg/kg). After treatment the 

rats received stock diet and tap water ad libitum. They were observed for signs of 

intoxication during a 14 day period, after which necropsies were carried out on the 

survivors. The LD50 was calculated according to the method of Weil (Biometrics8 

(1952) 249-263). Within a few hours after dosing the rats showed sluggishness, sedation 

and ataxia but specific doses were not reported. Unconsciousness was frequently 

observed and preceded death. Most of the deaths occurred between 8 and 23 hours after 

treatment. One female died on the 4th and one male on the 7th post-treatment day and 

again the dose information was not reported. After 7 days the survivors recovered 

gradually and looked quite healthy again at the end of the observation period. 

Macroscopic examination of the survivors did not reveal any treatment-related gross 

alterations. From the mortality figures the LD50 of 1,3-propanediol was calculated to be 

14.9 ml per kg body weight(>15,000 mg/kg bw assuming 100% purity) with 13.7 and 

16.3 as the 95% confidence limits. Therefore, the material can be classified as practically 

non-toxic. 

Dermal Toxicity

No studies available in the database.

Inhalation Toxicity

In a acute inhalation study (MRID 48422619), six male Crl:CD(SD)BR rats were 

exposed nose-only for a single, four-hour period to 1,3-porpanediol aerosol at 5.0 mg/L 

(238 mg/kg). Test atmospheres were generated by aerosolization and concentrations of 

1,3-propanediol were measured by gravimetric analysis. Rats were weighed and observed 

for clinical signs of toxicity during a 14-day recovery period. Rats were exposed to the 

aerosol of 1,3-propanediol at a concentration of 5.0 mg/L (238 mg/kg). The mass median 

aerodynamic diameter for the aerosol tested was 3.2μm (within respirable range). All rats 

exposed to 1,3-propanediol survived the exposure and subsequent 14-day recovery 

period. Wet fur/perineum and ocular discharge were noted in rats immediately following 

the exposure and were the only clinical signs observed during the study. All rats 

exhibited slight to moderate weight loss one day after exposure. Although one rat had 

transient body-weight loss during the remainder of the recovery period, all rats 

experienced an overall weight gain by the end of the 14-day recovery period. Under the 

conditions of this study, the LC50 for 1,3-propanediol was greater than 5.0 mg/L (238 

mg/kg). On an acute inhalation basis, 1,3-propanediol is considered to be of very low 

toxicity. 

Primary Eye Irritation

In an acute eye irritation study (MRID 48422607), one male and one female albino rabbit 

was used. 1,3-Propanediol (0.2 mL) was instilled into the conjunctival sac of one eye of 

each rabbit; the untreated eye served as a control. A visual assessment of irritancy was 

made 30 minutes after application and again 1, 2, 3 and 7 days after application, thence 

every 4 days until eye irritancy was no longer observed. In this study, the formulation 

was mildly irritating up to 48 hrs after instillation. 
10

In another acute eye irritation study (MRID 48439011), six New Zealand white albino 

rabbits are used for each test substance. The animals were caged individually and receive 

no hay or other extraneous material that might enter the eyes. The eyes of the animals 

were examined before testing and only those animals without observable eye defects 

were used. One tenth of a millilitre of the test substance were allowed to fall on the 

inverted lower lid of one eye of each rabbit; the upper and lower eye lid were then 

carefully closed and subsequently held together for at least one second before releasing, 

to prevent loss of material. The other eye, remaining untreated, serves as a control. The 

eyes were not washed following instillation and the animals were released immediately. 

The eyes were examined at 24, 48, 72 hours and 7 days after instillation of the test 

material. The ocular effects of propanediol-1,3 consisted of slight redness of the 

conjunctivae in four out of six rabbits. After 48 hours these effects cleared up. In this 

study, the formulation was minimally irritating

Primary Skin Irritation

In an acute dermal irritation study (MRID 48422607), the occluded patch test of Draize 

was used to assess the skin irritation potential of undiluted 1,3-propanediol to abraded 

and intact rabbit skin (4/sex). Lint patches were applied to the abraded and intact skin and 

0.5ml test material was applied to each. The patches were left in place for 24 hours. 

Reactions were assessed visually for the degree of erythema and edema. Seven days after 

the application of the test material a final visual assessment was made. In this study, the 

formulation was mildly irritating with no signs of skin irritation 3 days after the exposure 

period. 

In another acute dermal irritation study (MRID 48439011), twelve healthy adult New 

Zealand White albino rabbits were used. Twenty four hours prior to applying the 

materials, the hair was removed from the backs of the animals. An amount of 0.5 ml of 

the test substance was brushed on the intact or abraded skin under a surgical patch 

measuring 1 inch x 1 inch. The patches were fixed to the application site by means of 

adhesive tape and the entire trunks of the rabbits were wrapped with an impervious 

material to maintain the test patches in position and to retard evaporation of volatile 

substances. Six rabbits were treated on the intact skin, the other six on the abraded skin. 

The abrasions were minor incisions through the stratum corneum, but not sufficiently 

deep to disturb the derma or to produce bleeding. After an exposure period of 24 hours 

the patches and the material applied were removed and the resulting skin reactions were 

evaluated by the method of Draize. A second reading was made 48 hours later (72 hours 

after application). In this study, the formulation was slightly irritating, which consists of 

very slight erythema and edema which was cleared after 72 hrs. 

Dermal Sensitization

In a skin sensitization study (MRID 48422635), a total of 32 young male albino SPF 

guinea pigs, were randomly divided into 4 groups. Two control groups and two test 

groups comprising 8 animals each. One control and one test group was used for each of 

the test samples. The test animals were treated with intradermal injection of 0.1 mL of a 

25% aqueous dilution for the induction period. A 10% aqueous dilution was used for the 

challenge dose. The test samples caused mild to severe skin reactions upon repeated 
11

intradermal injections in all animals during the induction period. There were no 

significant differences between test and control animals with respect to the degree and 

incidence of erythema and edema. From the results obtained it may be concluded that no 

sensitization occurred upon treatment with the two products tested. Based on the results 

of this study, 1,3-propanediol is not considered to be a contact sensitizer.

In a separate skin sensitization study (MRID 48422607), the guinea-pig maximization 

test as described by Magnusson and Kilgman, was used to assess the skin sensitization 

potential of 1,3-propanediol. Intradermal induction was performed at 2.5% w/v 1,3-

propanediol in water. A topical induction was tested and undiluted. The topical challenge 

was 50% 1,3-propanediol in water. Based on the results of this study, 1,3-propanediol is 

not considered to be a contact sensitizer.

The results of the available acute toxicity studies are summarized in Table 3.

Acute Toxicity

Table 3. Acute Toxicity Profile of 1,3-Propanediol

Study Type Results

Toxicity 

Category

MRIDs # 

/Reference

Acute Oral - rat LD50 = 10,500 mg/kg bw (Range Finding) N/A 48422607

Acute Oral - rat LD50 = 15,789 mg/kg bw IV 48422633

Acute Dermal - N/A N/A N/A

Acute Inhalation - rat NOAEL > 5.0 mg/L IV 48422619

Primary Eye Irritation - rabbit Minimal effects, clearing in less than 24 hrs IV 48422607

Primary Eye Irritation - rabbit Minimal effects, clearing in less than 24 hrs IV 48439011

Primary Skin Irritation - rabbits Mild Erythema and edema, no signs after 72 

hrs

IV 48422607

Primary Skin Irritation - rabbits Slight to mild Erythema, slight to no signs 

after 72 hrs

IV 48439011

Dermal Sensitization – guineapigsProduct is not a sensitizer Neg. 48422607

Dermal Sensitization – guineapigsProduct is not a sensitizer 48422635

Subchronic Inhalation Toxicity – Rat

In a 14 day inhalation toxicity study (MRID 48439008) three groups of 10 male Crl:CD 

(SD) IGS BR rats each were exposed by inhalation to either vapor only or a vapor/aerosol 

mixture of 1,3-propanediol in air at concentrations targeted to 60, 600, or 1800 mg/m3

(0.06, 0.60 or 1.80 mg/L) for 6 hours/day, 4 or 5 days/week for a total of 9 exposures. A 

procedural control group of 10 male rats were exposed simultaneously to air only. Rats 

were weighed prior to each exposure and were observed for clinical signs prior to, during, 

and following each exposure. At the end of the exposure period, clinical pathology 

evaluations were conducted on 10 rats/group, and 5 rats/group were sacrificed and 

necropsied. At the end of the 18-day recovery period, the 5 surviving rats/group were 

given clinical pathology examinations, then sacrificed and necropsied. All rats were 

examined for gross and microscopic changes. The analytically determined mean 

concentrations of 1,3-propanediol in the exposure chambers were 41, 650 and 1800 

mg/m3 (0.041, 0.650, and 1.800 mg/L) over the duration of the study. All rats survived to 
12

the termination of the study and were sacrificed by design. There were no test substancerelated clinical signs of toxicity observed during the study. No statistically significant 

body weight differences were observed in any group. There were no compound-related 

adverse effects noted during clinical pathology or pathology evaluations. The NOAEL for 

repeated inhalation exposure to 1,3-propanediol in male rats was considered to be 1800 

mg/m3 or 1.8 mg/L.

Subchronic Oral Toxicity – Rat

In a 90-day oral toxicity study (MRID 48439004), 1,3 Propanediol (purity not reported; 

Lot no. D47617, 09/06/96) was administered to 10 Crl:CD®(SD)BR rats/sex/dose by 

gavage at dosages of 0, 100, 300 or 1000 mg/kg/day. Reverse osmosis-treated water was 

administered to controls. All animals survived to the scheduled necropsy. No test articlerelated changes in the clinical condition of the animals were observed. Mean body 

weights, body weight gains, food consumption, clinical pathology parameters 

(hematology, serum chemistry) and organ weights were unaffected by test article 

administration. No treatment related effects were observed on eyes at ophthalmoscopic 

examinations conducted at the end of the study. Spermatogenic endpoints were 

unaffected in all treated males. No treatment-related changes were observed at the 

macroscopic and microscopic examinations. Based on the data obtained, the no-observedadverse-effect level (NOAEL) for systemic toxicity of 1,3-Propanediol administered 

orally via gavage to male and female rats for 91 or 92 consecutive days was 1000 

mg/kg/day.

Chronic Oral Toxicity -

No chronic studies were available in the database.

Developmental and Reproductive Toxicity - Rats

1,3-Propanediol, Polymer Grade (99.8% a.i) was administered to 20 pregnant female 

Sprague-Dawley (Hag: SD) rats/dose by gavage in 0.8% aqueous hydroxypropylmethylcellulose gel (with constant dose volume of 10 mL/kg bw or 10,000 mg/kg) at 

dose levels of 0, 250, or 1000 mg/kg bw/day on gestation days (GDs) 6 through 15. 

Dams were sacrificed and necropsied on GD 20. All fetuses were weighed, sexed, 

measured, and examined externally; approximately one-half were subjected to visceral 

examination, and the remaining one-half were subjected to skeletal examination. All 

placentae were weighed individually. There were no treatment-related effects on maternal 

survival, clinical signs, body weight, food consumption, or gross pathology. The 

maternal LOAEL is not identified, and the maternal NOAEL is greater than or equal to 

1000 mg/kg bw/day. There were no treatment-related effects on live litter size, fetal 

deaths, early or late resorptions, or the fetal sex ratio. Mean fetal weights, fetal lengths, 

and placental weights of the treated groups were similar to those of controls. 

Malformations were only observed in one fetus from a control litter, and there were no 

significant increases in the litter incidences of any individual morphological variation or 

retardation for either treated group. The developmental LOAEL is not identified, and the 

developmental NOAEL is greater than or equal to 1000 mg/kg bw/day.

Immunotoxicity

No immunotoxicity studies were available in the database.
13

Neurotoxicity

No neurotoxicity studies were available in the database.

Mutagenicity and Genotoxicity

In a reverse gene mutation assay in bacteria (MRID 48439014), strains TA98, TA100, 

TA102, TA1535 and TA1537 of S. typhimurium were exposed to 1,3-propanediol 

(≥99.8% a.i., lot number EK 33/92-1) dissolved in double distilled water in two 

independent assays using triplicate plating. A cytotoxicity assay in strains TA98 and 

TA100 tested concentrations of 0, 3.3, 10, 33.3, 100, 333.3, 1000, 2500, or 5000 μg/plate 

with and without S9-mix. The first mutagenicity assay used the plate incorporation 

method at concentrations of 0, 33.3, 100, 333.3, 1000, 2500, or 5000 μg/plate with and 

without S9-mix. The second mutagenicity assay used the pre-incubation method at the 

same concentrations with and without S9-mix. The test material 1,3-propanediol was 

tested at concentrations up to the limit concentration for the assay, and there was no 

evidence that the assays were affected by cytotoxicity or insolubility. The number of 

revertants per plate was not increased over the concurrent solvent control value at any test 

material concentration, with or without S9-mix, in any test strain. The solvent and 

positive controls induced the appropriate responses in the corresponding strains. There 

was no evidence of induced mutant colonies over background.

In an in vitro mammalian cell chromosome aberration assay (MRID 48422613), Chinese 

hamster V79 cells were exposed to 1, 3-propanediol (Haskell Number H-24783, 99.9% 

purity) in culture medium with and without activation. The concentrations tested were 0, 

625, 1250, 2500, and 5000 μg/mL. Without activation (-S9 mix), the exposures were 

either for 4 hours, followed by a recovery time of 16 hours before cell harvest or an 

exposure time of 20 hours followed immediately by cell harvest. With activation (+S9 

mix), the exposures were for 4 hours, followed by a recovery time of 16 hours before cell 

harvest. The S9-fraction was obtained from Aroclor 1254-induced male Sprague-Dawley 

rat liver.

In a cytotoxicity pre-test experiment, no toxicity effects (as measured by cell killing) 

were noted either with or without activation up to the limit concentration for the assay of 

5000 μg/mL. This established the doses to be used in the cytogenetic tests (0, 625, 1250, 

2500, and 5000 μg/mL). The cytogenetic tests showed that there were no significant 

increases in the percentages of metaphase cells with structural chromosomal damage or 

polyploid cells over the solvent control values, either without or with activation. Within 

the evaluated concentration ranges, both with and without activation, the mitotic indices 

were not significantly reduced.

In an in vitro mammalian cell chromosome aberration assay (MRID 48439012), Chinese 

hamster V79 cells were exposed to 1,3-propanediol (99.8% purity, Batch # EK 33/92-1) 

in culture medium in two separate experiments. In experiment I, without activation, the 

concentrations tested were 0, 250, 1000, and 2500 μg/mL and the exposures were for 18 

hours, followed by cell harvest (18-hour mutation fixation period); with activation (S9 

mix), the concentrations tested were 0, 500, 2500, and 5000 μg/mL and the exposures 
14

were for 4 hours, with a 14-hour recovery period before harvest (18-hour mutation 

fixation period). In Experiment II, without activation, the concentrations tested were 0, 

375, 1250, and 2500 μg/mL (18-hour fixation interval) and 0 and 1250 μg/mL (28-hour 

fixation interval). In experiment II, with activation, the concentrations tested were 0, 

2500, 3750, and 5000 μg/mL (18-hour fixation interval) and 0 and 5000 μg/mL (28-hour 

fixation interval). In experiment II, the treatments lasted 4 h with S9 mix and for the 

entire fixation interval without S9 mix.

In the same study, a cytotoxicity pre-test experiment showed no toxicity effects were 

noted either with or without activation up to the limit concentration for the assay of 5000 

μg/mL. However, in the cytogenetic experiments in the absence of activation, evaluations 

were only possible up to a concentration of 2500 μg/mL (18-hour mutation fixation 

period) and 1250 μg/mL (28-hour mutation fixation period) because of low cell and 

metaphase numbers as well as poor metaphase quality at higher doses. With activation, 

test groups were scorable up to 5000 μg/mL. Within the evaluated concentration ranges, 

both with and without activation, the mitotic indices were not significantly reduced. In 

both experiments I and II, there were statistically significant and biologically relevant 

increases in the chromosome aberration frequencies after treatment with 2500 μg/mL 

(highest dose attainable) of the test material without activation. With activation, there 

were no increases in chromosome aberration frequencies in either experiment, up to the 

maximum dose of 5000 μg/mL. In both experiments there were no increases in the 

frequencies of polyploid metaphases at any dose level, either with or without activation. 

The positive controls used in both experiments gave appropriate responses.

In a mammalian cell gene mutation assay at the hypoxanthine-guanine phosphoribosyl

transferase (HGPRT) locus (MRID 48439013), Chinese hamster V79 cells cultured in 

vitro were exposed to 1, 3-propanediol (≥99.8% a.i., Batch No. EK 33/92-1) dissolved in 

culture medium at concentrations of 0, 250, 1000, 2500, or 5000 μg/mL in the absence 

and presence of mammalian metabolic activation for 4 hours. The test chemical, 1, 3-

propanediol, was tested up to the limit concentration for the assay. There were no 

indications of insolubility. The cytotoxicity pretest provided no evidence of cytotoxicity, 

either with or without metabolic activation. However, in both independent mutagenicity 

experiments I and II, in the absence of metabolic activation the cloning efficiencies 

showed significant decreases at 1000, 2500 and 5000 μg/mL. The cell density at the first 

subculturing was only slightly reduced at 2500 μg/mL, being 77.2 % and 75.1% of the 

control values in experiments I and II, respectively. At the highest test concentration of 

5000 μg/mL, there was a marked reduction of the cell density at first subculturing, to 

37.8 % and 14.4 % in Experiments I and II, respectively. The only slight suggestions of 

any increases in the mutation rate by the test material were not considered biologically 

significant because (1) the corresponding solvent controls had relatively low mutation 

rates in these experiments, (2) the mutation rates of the treated cells were well within the 

historical control range (0-45 mutants/106 cells), and (3) there were no hints of any 

increases in response to increasing concentrations. The positive controls did induce the 

appropriate response. There was no evidence of induced mutant colonies over 

background.
15

In a Hsd/Win: NMRI mouse bone marrow micronucleus test (MRID 48439005), 14 

mice/sex were administered 2150 mg/kg of 1,3-propanediol (Batch No. EK 33/92-1, 

99.8% pure) dissolved in water via gavage. Half the animals were sacrificed 24 hours 

after treatment and half were sacrificed 48 hours after treatment, with the bone marrow 

cells being harvested immediately upon sacrifice. In all experiments, slides from five 

animals per sex and group were examined, with 1000 polychromatic erythrocytes (PCEs) 

being examined for micronuclei per mouse. The ratio of PCEs to normochromatic 

erythrocytes (NCEs) was always based on 1000 erythrocytes (PCEs + NCEs) scored per 

slide for every mouse. In the experiment, 1,3-propanediol was tested only at 2150 mg/kg 

because a preliminary toxicity assay showed that this was the maximum practicable dose 

and it exceeded the guideline requirements for a limit dose of 2000 mg/kg. There was no 

reduction in the PCE/NCE ratio at either sampling-time (24 or 48 hours) in this 

experiment. There was also no statistically significant test-article-related increase in 

micronucleated polychromatic erythrocytes in either male or female animals when 

compared with corresponding negative control group animals at the 24- and 48-hour 

sampling times. The same was true for the evaluation of the data of both sexes combined 

at the 24-hour sampling time. However, at the 48-hour sampling time a slight, statistically 

significant increase (p = 0.029) in micronucleated polychromatic erythrocytes was 

present. To determine whether this increase indicated a potential mutagenic activity of 

the test material, according to the test guideline, a second test (repeat experiment) was 

performed to examine the reproducibility of the statistically significant response at the 

48-hour sampling time in males and females combined, and to assess a possible dose 

relation in the increase of micronucleated polychromatic erythrocytes. In the repeat 

experiment, after a single oral administration of the test material at 1000, 1470, or 2150 

mg/kg, there was again no reduction in the PCE/NCE ratio at any test dose when 

compared with the corresponding negative control group. There was no statistically 

significant test article-related increase in micronucleated polychromatic erythrocytes in 

either male or female animals analyzed separately, or in males and females combined, 

when compared with corresponding negative control group animals at the 48-hour 

sampling time after treatment. There was no dose-related increase in the number of 

micronucleated polychromatic erythrocytes in either sex. The statistically significant 

positive response in males and females combined for the 48-hour sampling time in the 

experiment was therefore not verified during the repeated test using two additional dose 

levels and was, accordingly, considered to be biologically insignificant. The vehicle 

(saline) controls had acceptable micronuclei frequencies. The positive control mice 

(males and females treated with cyclophosphamide) showed statistically significant 

increases in the frequency of micronuclei, indicating that the assay was working properly. 

Under the experimental conditions reported, 1,3-propanediol was considered to not be 

mutagenic in mice as measured by damage to chromosomes or the mitotic apparatus.

Carcinogenicity

No carcinogenicity studies were available in the database. However based on lack of 

mutagenicity concern, lack of any systemic toxicity up to limit dose in the available 

studies, and lack of any structural alerts for carcinogenicity in Derek analysis, EPA 

concluded that 1,3-propanediol is not expected to pose a cancer risk. 
16

Metabolism and Pharmacokinetics

The proposed metabolic pathway for 1,3-propanediol follows that for other simple 

alcohols, where alcohol and aldehyde dehydrogenase enzymes sequentially break down 

this substance to acids used in intermediary metabolism. 1,3-propanediol is metabolized 

to 3-hydroxypropionaldehyde, malondialdehyde or 3-hydroxypropionic acid, malonic 

semi-aldehyde, malonic acid, and ultimately carbon dioxide and water. 

Table 4. Toxicology Profile for 1,3-Propanediol

Guideline No./ 

Study Type

Doses Levels MRID No. 

(year)/References

Results

2-week Inhalation 

Toxicity study (rats)

0, 41, 650, 1800 

mg/m3

(0, 0.041, 0.650, 

1.800 mg/L)

MRID48439008

Scott (1998)

LOAEL = was not established

NOAEL = 1800 mg/m3 or 1.800 mg/L

90-Day Oral 

Toxicity Study 

(rats)

Male: 0, 100, 

300, 1000 mg/kg 

bw/day

Female: 0, 100, 

300, 1000 mg/kg 

bw/day

MRID: 48439004

Kirkpatrick (1999)

LOAEL = was not established.

NOAEL = 1,000 mg/kg bw/day

Developmental 

Toxicity (rats)

0, 250, 1000 

mg/kg bw/day

MRID: 48439006

Leuschner (1992)

Maternal LOAEL was not established.

Maternal NOAEL = 1,000 mg/kg/day

Developmental LOAEL was not established. 

Developmental NOAEL = 1,000 mg/kg/day

Bacterial Reverse 

Mutation Test

0, 3.3, 10, 33.3, 

100, 333.3, 

1000, 2500, 

5000 μg/plate

MRID: 48439014

Wollny (1994)

No evidence of induced mutant colonies over 

background.

In vitro mammalian 

Cell Gene Mutation 

Test

0, 250, 1000, 

2500, 5000 

μg/mL

MRID: 48439013

Wollny (1994)

No evidence of induced mutant colonies over 

background.

In Vitro

Chromosome 

Aberration Assay

0, 625, 1250, 

2500, 5000 

μg/mL

MRID: 48422613

Gudi (2001)

No evidence of induction of structural and 

numerical chromosome aberrations.

in vitro mammalian 

cell chromosome 

aberration assay

Variable for each 

test with a 

maximum of 

5000 μg/mL.

MRID: 48439012

Wolfgang (1994)

Under the experimental conditions reported, the 

test article 1,3-propanediol reproducibly induced 

structural chromosomal aberrations in the V79 

Chinese hamster cell line.

Mammalian 

Erythrocyte 

Micronucleus Test

2150 mg/kg bw MRID: 48439005

Krauser (1995)

1,3-propanediol, did not induce micronuclei in 

bone marrow erythrocytes of mice (males and/or 

females) given a single oral dose of the test 

material up to a maximum dose of 2150 mg/kg, 

and then assayed at 24 and 48 hours posttreatment.

B. Toxicity Endpoint Selection

No toxicological endpoints have been identified for 1,3-propanediol due to no adverse 

observable effects seen in toxicity studies with doses up to 1,000 mg/kg/day. 
17

C. Special Considerations for Infants and Children

EPA did not use a safety factor analysis for assessing risk because no systemic toxicity or 

developmental toxicity was seen in the developmental toxicity study in rats. No systemic

toxicity was seen in the 90-day toxicity study in rats via gavage at doses up to 1,000 

mg/kg/day. 

IV. EXPOSURE ASSESSMENT

In conducting a dietary exposure assessment using the Dietary Exposure Evaluation 

Model DEEM-FCIDTM, Version 3.16, EPA used food consumption information from the 

U.S. Department of Agriculture’s National Health and Nutrition Examination Survey, 

What we eat in America, (NHANES/WWEIA). This dietary survey was conducted from 

2003 to 2008. As to residue levels in food, no residue data were submitted for 1,3-

propanediol. 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.

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 ingredients 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 
18

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, and then use 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. 

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.

A. Dietary Exposure:

In evaluating dietary exposure to 1,3-propanediol, EPA considered exposure 

under the proposed exemption from the requirement of a tolerance (40 CFR 180.940(a)) 

and as an inert ingredient used in pesticide formulations applied to growing crops (40 

CFR 180.910). EPA assessed dietary exposures from 1,3-propanediol as follows:

In the absence of actual dietary exposure data resulting from this proposed use the 

EPA has utilized a conservative, health-protective method of estimating dietary intake 

that is based upon conservative assumptions related to the amount of residues that can be 

transferred to foods as a result of the proposed use of 1,3-propanediol in food contact 

sanitizing pesticide products. This same methodology has been utilized by EPA in 

estimating dietary exposures to antimicrobial pesticides used in food-handling settings. 

The Agency believes the assumptions used to estimate chronic dietary exposures lead to 

an extremely conservative assessment of dietary risk due to a series of compounded 

conservatisms as described in the unit. First, when a surface is treated with a disinfectant, 

a quantity of the disinfectant remains on the surface (Residual Solution). In the absence 

of any other data, EPA has used an estimated worst-case concentration of 1mg of solution 

per square centimeter (cm2) of treated surface area for this quantity. Second, the 

conservatism of this methodology is compounded by EPA’s decision to assume a worst 

case scenario that all food that an individual consumes will come into contact with 4,000 

cm2 of sanitized non-porous food-contact surfaces. This contact area represents all the 

surface area from silverware, china, and glass used by a person who regularly eats three 

meals per day at an institutional or public facility. The surface area of counter tops that 

comes in contact with food is expected to be smaller than the surface area for food 
19

utensils. As a conservative estimate, EPA assumed that 2,000 cm2 of treated counter top 

surface area, comes into contact with an individual’s food per day. Third, EPA assumes 

that 100% of the material presented on food contact surfaces will migrate to food.

 i. Acute exposure. No adverse effects attributable to a single exposure of 1,3-

propanediol were seen in the toxicity databases. Therefore, acute dietary risk assessment 

for 1,3-propanediol is not required.

 ii. Chronic exposure. No adverse effects attributable to a chronic exposure of 1,3-

propanediol were seen in the toxicity databases. Therefore, chronic dietary risk 

assessment for 1,3-propanediol is not required.

iii. Cancer exposure. 1,3-Propanediol is not expected to be carcinogenic. Therefore, a 

cancer dietary exposure assessment is not necessary to assess cancer risk.

B. Residential Exposure

The term “residential exposure” is used in this document to refer to non-occupational, 

non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, 

termiticides, and flea and tick control on pets). Due to the absence of a toxicity endpoint 

for 1,3-propanediol in the database, residential exposure is not expected to be of concern. 

Therefore a quantitative residential exposure risk assessment was not performed.

V. AGGREGATE RISK AND DETERMINATION OF SAFETY

EPA determines whether acute and chronic pesticide exposures are safe by comparing 

aggregate exposure estimates to the aPAD and cPAD. The aPAD and cPAD represent the 

highest safe exposures, taking into account all appropriate safety factors (SFs). EPA calculates 

the aPAD and cPAD by dividing the POD by all applicable UFs. For linear cancer risks, EPA 

calculates the probability of additional cancer cases given the estimated aggregate exposure. 

Short-, intermediate-, and chronic-term risks are evaluated by comparing the estimated aggregate 

food, water, and residential exposure to the POD. The MOE is the product of all applicable UFs 

and should not be exceeded. 

A. Acute Dietary Risk. An acute aggregate risk assessment takes into account exposure 

estimates from acute dietary consumption of food and drinking water using the exposure 

assumptions discussed in section IV for acute exposure and the use limitations in 

pesticide formulations. However there was no hazard attributable to a single exposure 

seen in the toxicity database for 1,3-propanediol; therefore an acute aggregate risk 

assessment is not required. 

B. Chronic Dietary Risk. A chronic aggregate risk assessment takes into account 

exposure estimates from chronic dietary consumption of food and drinking water using 

the exposure assumptions discussed in section IV for chronic exposure and the use 
20

limitations in pesticide formulations. However there was no hazard attributable to 

chronic exposures in the toxicity database for 1,3-propanediol, therefore an chronic 

aggregate risk assessment is not required.

C. Aggregate Cancer Risk for U.S. Population. The Agency has not identified any 

concerns for carcinogenicity relating to 1,3-propanediol; therefore, a cancer dietary 

exposure assessment was not performed and an aggregate risk assessment is not a 

concern.

D. Short-Term Aggregate Risk. Short-term aggregate exposure takes into account 

short-term residential exposure plus chronic exposure to food and water (considered to be 

a background exposure level). 1,3-Propanediol is used as an inert ingredient in pesticide 

products that are currently registered for uses that could result in short-term residential 

exposure however no adverse effects were attributable to chronic exposure to 1,3-

propanediol were seen in the toxicity database; therefore, a short-term aggregate risk 

assessment is not required. 

E. Intermediate-Term Aggregate Risk. Intermediate-term aggregate exposure takes 

into account intermediate-term residential exposure plus chronic exposure to food and 

water (considered to be a background exposure level). 1,3-Propanediol is used as an inert 

ingredient in pesticide products that are currently registered for uses that could result in 

intermediate-term residential exposure however no adverse effects were attributable to 

chronic exposure to 1,3-propanediol were seen in the toxicity database; therefore, an

intermediate-term aggregate risk assessment is not required. 

F. Determination of Safety. EPA concludes that there is a reasonable certainty that no 

harm will result to the general population or to infants and children from aggregate 

exposure to residues of 1,3-propanediol.

VI. OCCUPATIONAL EXPOSURE/RISK PATHWAY

The representative occupational scenarios selected by the Agency for assessment are

evaluated based on likely maximum application rates for products which may contain the inert 

ingredient for the short-term exposure assessment, and average application rates for products 

likely to contain the inert ingredient for the intermediate- and long-term exposure durations. 

Active ingredient application rates are corrected for the maximum amount of inert ingredient

likely to be in the final formulations to determine exposure and risk from exposure to the inert 

ingredient by fungicide, insecticide or herbicide. 

RD traditionally considers a level of concern (LOC) for these risk assessments to be an 

MOE of 100 based on the standard 10X inter and 10X intra species extrapolation safety factors 

and additional uncertainty in the database.

A. Occupational Handler Risk
21

Exposure Scenarios

Due to the absence of dermal and inhalation toxicity end points, occupational handler 

risks are not of concern. Therefore an occupational handler risk assessment was not 

performed.

B. Occupational Post-Application Risk

Exposure Scenarios

RD uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred 

to as re-entry exposure). Such exposures may occur when workers enter previously 

treated areas to perform job functions, including activities related to crop production, 

such as scouting for pests or harvesting. Post-application exposure levels vary over time 

and depend on such things as the type of activity, the nature of the crop or target that was 

treated, the type of pesticide application, and the chemical’s degradation properties. In 

addition, the timing of pesticide applications, relative to harvest activities, can greatly 

reduce the potential for post-application exposure. Inhalation exposures are not typically 

calculated for occupational post-application scenarios because inhalation exposures 

generally account for a negligible percentage of the overall body burden for most 

pesticide chemicals. 

Due to the absence of dermal and inhalation toxicity endpoints, occupational postapplication risks are not of concern. Therefore an occupational post-application risk 

assessment was not performed.

VII. CUMULATIVE EXPSOURE 

Cumulative effects from substances with a common mechanism of toxicity. Section 

408(b)(2)(D)(v) 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.”

EPA has not found 1,3-propanediol to share a common mechanism of toxicity with any 

other substances, and that 1,3-propanediol does not appear to produce a toxic metabolite 

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

assumed that 1,3-propanediol does not have 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 

EPA's website at http://www.epa.gov/pesticides/cumulative.
22

VIII. ENVIRONMENTAL JUSTICE STATEMENT 

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

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

Actions to Address Environmental Justice in Minority Populations and Low-Income 

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

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

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

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

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

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

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

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

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

specialized subgroups and exposure assessments are performed when conditions or 

circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of 

pesticide products and associated risks for adult applicators and for toddlers, youths, and adults 

entering or playing on treated areas post-application are evaluated. Further considerations are 

currently in development as OPP has committed resources and expertise to the development of 

specialized software and models that consider exposure to bystanders and farm workers as well 

as lifestyle and traditional dietary patterns among specific subgroups

IX. ENVIRONMENTAL FATE CONSIDERATIONS

Based on a Biodegradability study (Berti 2007) (MRID 48422603), the compound 1,3-

propanediol is readily biodegradable. Based on physico-chemical properties, 1,3-propanediol is 

water soluble and will partition to the soil. The low Kow (-0.71) suggests that 1,3-propanediol is 

not expected to absorb by sediment or suspended solids. The study showed that 71% of the 

compound was converted to CO2 after 28 days suggesting that the substance was completely 

mineralized without any major metabolites or degradation products. Due to its rate of 

biodegradation, 1,3-propanediol is not expected to be of major environmental fate concern.

X. ECOTOXICITY

In an acute invertebrate toxicity study (Kuhn R. et al. 1989), Daphnia magna, 6-24 hours 

old, were placed in each test and control vessel, i.e. 20 animals per concentration step. After a 

test period of 24 hours and again after 48 hours, the number of animals in the control and test 

solution that could still swim was counted. Both pH and oxygen content were monitored in the 

experiment to assure they were within acceptable ranges. The 24-hour EC50 was determined to 

be 8285 mg/L and 48-hour EC50 was determined to be 7417 mg/L. This concentration is above 

limit dose and therefore 1,3-propanediol is considered practically non-toxic on an acute basis to 

aquatic invertebrates. (MRID 48422622)
23

In an acute fish toxicity study (Samel, A. 2000), fathead minnows were tested in a static 

system at five nominal concentrations, 750, 1250, 2500, 5000 and 10,000 mg/L 1,3-propanediol, 

as well as a dilution water control. Each test chamber (15L) held 10 fish. A recirculating water 

bath was used to maintain a mean temperature of 22°C over the 96-hour test. Dissolved oxygen, 

pH and temperature were measured in all chambers/replicate chambers of control and test 

substance concentrations. No mortality or sublethal effects were seen in any of the test 

concentrations or in the water control fish. The 96-hour LC50 was determined to be greater than 

9720 mg/L, the mean measured concentration. This concentration is above the limit dose 

required for testing and therefore 1,3-propanediol is considered practically non-toxic on an acute 

basis to freshwater fish. (MRID 48422628)

In an algal toxicity study (Kamp, N. 1996), Scendesmus subspicatus was used to test 

growth rate through biomass production after 72 hour incubation in different dilutions of 1,3-

propanediol. Algae in a solution without any test substance served as control. A stock solution 

with 12.5 g test substance dissolved in deionized water was prepared along with the follow test 

concentrations: 0.5, 1.0, 2.0, 4.0, 8.0 and 10g per liter. The test and control solutions were 

incubated for a period of 72 hours at 25 °C and at an illumination rate of ~8000 lux. The EbC50

(inhibition of biomass after 72 hours) is 1.6 g test substance per liter of deionized water and the 

ErC50 (inhibition of growth rate after 72 hours) is > 10 g test substance per liter of deionized 

water. The NOEC was ≤ 0.5 g test substance per liter of deionized water. Based on these values, 

1,3-propanediol is considered practically non-toxic to algae. (MRID 48439002)

XI. RISK CHARACTERIZATION 

Dupont Tate & Lyle BioProducts Company. (198 Blair Bend Drive, Loudon, TN 37774) 

submitted a petition (PP 2E8091), requesting an exemption from the requirement of a tolerance 

pursuant to section 408(d)(1) of the Federal Food, Drug, and Cosmetic Act with respect to 1,3-

propanediol (CAS Reg. No. 504-63-2) as an inert ingredient for pre- and post-harvest (40 CFR 

180.910) and antimicrobial food-contact surface sanitizing formulations (40 CFR 40180.940). 

EPA published the Notice of Filing for this petition in the Federal Register on January 16, 2013 

(78 FE 3377). No substantial comments were received in response to this notice. 1,3-Propanediol 

was approved for non-food use in 2011. The majority of the data in this risk assessment decision 

document has been taken from the 2011 non-food use decision document.

The acute oral toxicity of 1,3-propanediol in rodents, expressed as an LD50 ranges from 

10,500 to 15,789 mg/kg bw. No acute dermal toxicity studies for 1,3-propanediol were available 

in the toxicity database. The acute inhalation toxicicty of 1,3-propanediol in rats produced a LC50

was > 5.0 mg/L. Primary eye irritation studies of 1,3-propanediol on rabbits showed minimal 

effects, slight redness of the conjunctivae, and clearing in less than 24 hours. It is considered 

minimally irritating to the eyes of rabbits. Primary skin irritation studies with 1,3-propanediol 

showed slight to mild erythema and edema to rabbits but clearing after 72 hrs. It is considered 

mildly irritating to the skin of rabbits. Dermal sensitization studies on guinea-pigs showed that 

1,3-propanediol is not a sensitizer.
24

In a 14-day inhalation toxicity study (MRID 48439008) three groups of 10 male Crl:CD 

(SD) IGS BR rats each were exposed by inhalation to either vapor only or a vapor/aerosol 

mixture of 1,3-propanediol in air at concentrations targeted to 60, 600, or 1800 mg/m3 (0.06, 

0.60 or 1.80 mg/L) for 6 hours/day, 4 or 5 days/week for a total of 9 exposures. A procedural 

control group of 10 male rats were exposed simultaneously to air only. The analytically 

determined mean concentrations of 1,3-propanediol in the exposure chambers were 41, 650 and 

1800 mg/m3 (0.041, 0.650, and 1.800 mg/L) over the duration of the study. All rats survived to 

the termination of the study and were sacrificed at the end of the study duration. There were no 

test substance-related clinical signs of toxicity observed during the study. No statistically 

significant body weight differences were observed in any group. There were no compoundrelated adverse effects noted during clinical observations or pathology evaluations. The NOAEL 

for repeated inhalation exposure to 1,3-propanediol in male rats was considered to be 1800 

mg/m3 or 1.8 mg/L (the highest dose tested) and no LOAEL was identified.

In a 90-day oral toxicity study (MRID 48439004), 1,3-propanediol was administered to 

10 Crl:CD®(SD)BR rats/sex/dose by gavage at dosages of 0, 100, 300 or 1000 mg/kg/day. 

Reverse osmosis-treated water was administered to controls. All animals survived to the 

scheduled necropsy. No test article-related changes in the clinical condition of the animals were 

observed. Mean body weights, body weight gains, food consumption, clinical pathology 

parameters (hematology, serum chemistry) and organ weights were unaffected by test article 

administration. No treatment related changes were observed in eyes up on ophthalmoscopic 

examinations at the end of the study. Spermatogenic endpoints were unaffected in all treated 

males. No treatment-related changes were observed at the macroscopic and microscopic 

examinations. Based on the data obtained, the NOAEL for systemic toxicity of 1,3-propanediol 

administered orally via gavage to male and female rats for 91 or 92 consecutive days was 1000 

mg/kg/day (the highest dose tested) and no LOAEL was identified.

The mutagenic potential of 1,3-propanediol was evaluated in a bacterial reverse mutation 

test, an in vitro mammalian cell gene mutation test, an in vitro chromosome aberration assay, an 

in vitro mammalian cell chromosome aberration assay and a mammalian erythrocyte 

micronucleus test. These test were all negative except for the in vitro mammalian cell 

chromosome aberration assay which showed under the reported experimental conditions that 1,3-

propanediol reproducibly induced structural chromosomal aberrations in the V79 Chinese 

hamster cell line. However due to negative in vivo mouse micronucleus assay, there are no 

concern for clastogenicity. Based on the results of these studies, 1,3-propanediol is not 

considered to be mutagenic. 

No carcinogenicity studies on 1,3-propanediol were available in the toxicity database, 

however based on the lack of mutagenicity concerns, lack of any systemic toxicity at the limit 

dose and lack of any structural alerts for carcinogenicity in Derek analysis, , there are no 

concerns for carcinogenicity for 1,3-propanediol.

In a developmental toxicity study, 1,3-propanediol was administered to 20 pregnant 

female Sprague-Dawley (Hag: SD) rats/dose by gavage in 0.8% aqueous hydroxypropylmethylcellulose gel (with constant dose volume of 10 mL/kg bw) at dose levels of 0, 250, or 

1000 mg/kg bw/day on gestation days (GDs) 6 through 15. Dams were sacrificed and necropsied 
25

on GD 20. There were no treatment-related effects on maternal survival, clinical signs, body 

weight, food consumption, or gross pathology. The maternal LOAEL is not identified, and the 

maternal NOAEL is greater than or equal to 1000 mg/kg bw/day (the highest dose tested). There 

were no treatment-related effects on live litter size, fetal deaths, early or late resorptions, or the 

fetal sex ratio. Mean fetal weights, fetal lengths, and placental weights of the treated groups 

were similar to those of controls and there were no significant increases in the litter incidences of 

any individual morphological variation or retardation for either treated group. The 

developmental LOAEL is not identified, and the developmental NOAEL is greater than or equal 

to 1000 mg/kg bw/day (the highest dose tested).

There were no immunotoxicity or neurotoxicity studies on 1,3-propanediol available in 

the toxicity database. However, there was no evidence of clinical signs of neurotoxicity or 

immunotoxicity triggers in the available database up to the limit dose.

The proposed metabolic pathway for 1,3-propanediol follows that for other simple 

alcohols, where alcohol and aldehyde dehydrogenase enzymes sequentially break down this 

substance to aldehydes and acids used in intermediary metabolism. 1,3-propanediol is 

metabolized to 3-hydroxypropionaldehyde, malondialdehyde or 3-hydroxypropionic acid, 

malonic semi-aldehyde, malonic acid, and ultimately, carbon dioxide and water. 

EPA did not use a safety factor analysis for assessing risk because no toxicological 

endpoints have been identified for this chemical. 

Acute and chronic dietary risk assessments were not conducted because no endpoints of 

concern following single or multiple exposures were identified in the available studies. 1,3-

Propanediol is not expected to be carcinogenic. Therefore, a cancer dietary exposure assessment 

is not necessary to assess cancer risk.

The term “residential exposure” is used in this document to refer to non-occupational, 

non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, 

and flea and tick control on pets). Due to the absence of a toxicity endpoint for 1,3-propanediol 

in the database, residential exposure is not expected to be of concern. Therefore a quantitative 

residential exposure risk assessment was not performed.

Short-term aggregate exposure takes into account short-term residential exposure plus 

chronic exposure to food and water (considered to be a background exposure level). 1,3-

Propanediol is used as an inert ingredient in pesticide products that are currently registered for 

uses that could result in short-term residential exposure however no adverse effects were 

attributable to chronic exposure to 1,3-propanediol were seen in the toxicity database; therefore, 

a short-term aggregate risk assessment is not required. 

Intermediate-term aggregate exposure takes into account intermediate-term residential 

exposure plus chronic exposure to food and water (considered to be a background exposure 

level). 1,3-Propanediol is used as an inert ingredient in pesticide products that are currently 

registered for uses that could result in intermediate-term residential exposure however no adverse 
26

effects were attributable to chronic exposure to 1,3-propanediol were seen in the toxicity 

database; therefore, an intermediate-term aggregate risk assessment is not required. 

Due to the absence of dermal and inhalation toxicity, occupational handler and postapplication risks are not of concern. Therefore occupational handler and post-application risk 

assessments were not performed.

Based on a Biodegradability study (Berti 2007), the compound 1,3-propanediol is readily 

biodegradable. Based on physico-chemical properties, 1,3-propanediol is water soluble and will 

partition to the soil. The low Kow (-0.71) suggests that 1,3-propanediol is not expected to absorb 

by sediment or suspended solids. The study showed that 71% of the compound was converted to 

CO2 after 28 days suggesting that the substance was completely mineralized without any major 

metabolites or degradation products. Due to its rate of biodegradation, 1,3-propanediol is not 

expected to be of major environmental fate concern.

Based on 3 acute ecotoxicity studies, 1,3-propanediol is practically non-toxic to 

freshwater invertebrates, freshwater fish and algae. Freshwater invertebrate, Daphnia magna had 

a 24-hr EC50 of 8285 mg/L and a 48-hr EC50 of 7417 mg/L. The freshwater fish, fathead minnow 

had a 96-hr LC50 of 9720 mg/L. Lastly the algae, Scendesmus subspicatus, had a 72-hr EbC50of 

1.6g/L and a 72-hr ErC50 >10 g/L with a NOAEC ≤ 0.5 g/L.

Taking into consideration all available information on 1,3-propanediol, EPA concludes 

that there is a reasonable certainty that no harm to any population subgroup will result from 

aggregate exposure to 1,3-propanediol when considering occupation, dietary exposure and all 

other nonoccupational sources of pesticide exposure for which there is reliable information. 

Therefore, the establishment of an exemption from tolerance under 40 CFR 180.910 and 180.940 

for residues of 1,3-propanediol (CAS Reg. No. 504-63-2) when used as a pesticide inert 

ingredient for pre- and post-harvest (40 CFR 180.910) and antimicrobial food-contact surface 

sanitizing formulations (40 CFR 180.940), can be considered assessed as safe under section 

408(q) of the FFDCA. 
27

REFERENCES

Berti, W.R., Wolstenholme, B.W. (2007). 1,3-Propanediol: Assessment of Ready 

Biodegradability by the Co2 Evolution Test. Testing laboratory: Environmental and 

Microbiological Sciences & Engineering. Report No.: EMSER 10-06. Owner company: E.I. du 

Pont de Nemours and Company. MRID 48422603. Unpublshed.

Coombs, A.D., Clark, D.G. (1997). Acute toxicity, skin and eye irritation and skin sensitizing 

potential of trimethylene glycol. Testing laboratory: Experimental Toxicology Division of Shell 

Toxicology Laboratory Tunstall. Report no.: TLGR.0026.77. Owner company: Shell Chemical 

Co. MRID 48422607. Unpublished.

Gingell, R., Kirkpatrick, J.B., Steup, D.R. (2000). Subchronic Toxicity Study of 1,3-Propanediol 

Administered Orally to Rats. International Journal of Toxicology, 19:27-32. MRID 48422612.

Gudi, R., Brown, C. (2001). H-24783 In Vitro Mammalian Chromosome Aberration Test. 

Testing laboratory: BioReliance. Report no.: DuPont-5683. Owner company: E.I. DuPont de 

Nemours and Company. MRID 48422613. Unpublished.

Kamp, N. (1996a). Study on the Toxicity towards Algae of 1,3-Propanediol according to OECDTest Guideline 201, Edition dated June 7th, 1984. Testing laboratory: Institut Fresenius. Report 

no.: Degussa 95-0127-DGO. Owner company: E.I. DuPont de Nemours and Company. MRID 

48439002. Unpublished.

Kaur. G., Srivastava, A.K., Chand, S. (2012) Advances in biotechnological production of 1,3-

propanediol. Biochemical Engineering Journal Vol 64. Pg. 106-118. 

Kegelman, T.A. (1997). Inhalation Approximate Lethal Concentration (ALC) of H-22121 in 

Rats. Testing laboratory: Haskell Laboratory for Toxicology and Industrial Medicine. Report no.: 

HL-1997-00095. Owner company: E.I. DuPont de Nemours and Company. MRID 48422619. 

Unpublished

Kirkpatrick, J.B. (1999). A 90-Day Oral (Gavage) Study of 1,3-Propanediol in Rats. Testing 

laboratory: WIL Research Laboratories, Inc. Report no.: WIL-93128. Owner company: Shell 

Chemical Company. MRID 4849004. Unpublished.

Kranser, K. (1995). 1,3-Propanediol, Mouse Micronucleus Test (Single Oral Administration). 

Testing laboratory: ASTA Medica AG, Institute of Toxicology. Report no.: Degussa 94-0170-

DGM. Owner company: E.I. DuPont de Nemours and Company. MRID 48439005. Unpublished.

Kuhn, R., Pattard, M., Pernak, K.-D., Winter, A. (1989). Results of the Harmful Effects of 

Selected Water Pollutants (Anilines, Phenols, Aliphatic Compounds) to Daphnia magna. Water 

Research, 23(4):495-499. MRID 48422622. 
28

Leuschner, F. (1992). Examination of the Influence of 1,3-Propanediol, polymer Grade on the 

Pregnant Rat and the Fetus by Oral Administration. Testing laboratory: Laboratory of 

Pharmacology and Toxicology. Report no.: Degussa 92-0063-DGB. Owner company E.I. 

DuPont de Nemours and Company. MRID 48439006. Unpublished.

Mertens, J.J. W.M. (1997). A 14-Day Oral (Gavage) Range-Finding Study of 1,3-Propanediol in 

Rats. Testing laboratory: WIL Research Laboratories, Inc. Report no.: WIL-93127. Owner 

company: Shell Cheimcal Co. MRIS 48439007. Unpublished.

Samel, A. (2000). H-24503: Static, Acute, 96-Hour LC50 to the Fathead minnow, Pimphales 

promelas. Testing laboratory: Haskell Laboratory for Toxicology and Industrial Medicine. 

Report no.: DuPont-4185. Owner company E.I. DuPont de Nemours and Company. MRID 

48422628. Unpublished. 

Scott, R.S. (1998). H-23131: Two-Week Inhalation Toxicity Study in Male Rats. Testing 

laboratory: Haskell Laboratory for Toxicology and Industrial Medicine. Report no.: DuPont1167. Owner company: E.I. DuPont de Nemours and Company. MRID 48439008. Unpublished.

Spanjers, M.Th., Til, H.P. (1979). Determination of the Acute Oral Toxicity of Propane-1,3-Diol 

in Rats. Testing laboratory: Degussa, Frankfurt, W. Germany. Report no.: Degussa 79-0077-

DKT. Owner company: E.I. DuPont de Nemours and Company. MRID 48422633. Unpublished.

Til, H.P., Keizer, A.M.M. (1979). Sensitization potential of Propanediol-1,3 and its distillation 

residue in guinea pigs. Testing laboratory: Centraal instituut voor voedingsonderzoek. Report 

no.: Degussa 79-0078-DKT. Owner company: E.I. DuPont de Nemours and Company. MRID 

48422635. Unpublished

Van Beek, L. (1979). Primary skin and eye irritation tests with propanediol-1,3 in albino rabbits. 

Testing laboratory: Degussa Industrielle Toxikologie. Report no.: Degussa-79-0093-DKT. 

Owner company: E.I. DuPont de Nemours and Company. MRID 48439011. Unpublished.

Volkner, W. (1994). Chromosome aberration assay in Chinese hamster v79 cells in vitro with 

1,3-propanediol Testing laboratory: CCR (Cytotest Cell Research GMBH & Co.). Report no.: 

Degussa 94-0059-DGM. Owner company: E.I. DuPont de Nemours and Company. MRID 

48439012. Unpublished.

Wollny, E. (1994a). Gene mutation assay in Chinese hamster V79 cells in vitro (V79/HPRT) 

with 1,3-Propanediol. Testing laboratory: CCR (Cytotest Cell Research GMBH & Co.). Report 

no.: Degussa 94-0060-DGM. Owner company: E.I. DuPont de Nemours and Company. MRID 

4849013. Unpublished.

Wollny, E. (1994b). Salmonella typhimurium reverse mutation assay with 1,3-propanediol. 

Testing laboratory: CCR (Cytotest Cell Research GMBH & Co.). Report no.: Degussa 94-0058-

DGM. Owner company: E.I. DuPont de Nemours and Company. MRID 48439014. Unpublished. 
APPENDIX

Derek Nexus Report

Author

rkent

Report date

20 February 2013 12:24:09

Prediction date

20 February 2013 12:22:30

Program version

Derek Nexus: 3.0.1, Nexus: 1.5.0

Compound name

Structure

Species

bacterium, mammal

Endpoints

alpha-2-mu-Globulin nephropathy, Anaphylaxis, Bladder urothelial hyperplasia, Carcinogenicity, 

Cardiotoxicity, Cerebral oedema, Chloracne, Cholinesterase inhibition, Chromosome damage in vitro, 

Chromosome damage in vivo, Cumulative effect on white cell count and immunology, Cyanide-type 

effects, Developmental toxicity, Genotoxicity in vitro, Genotoxicity in vivo, Hepatotoxicity, HERG 

channel inhibition in vitro, High acute toxicity, Irritation (of the eye), Irritation (of the gastrointestinal 

tract), Irritation (of the respiratory tract), Irritation (of the skin), Lachrymation, Methaemoglobinaemia, 

Mutagenicity in vitro, Mutagenicity in vivo, Nephrotoxicity, Neurotoxicity, Occupational asthma, Ocular 

toxicity, Oestrogenicity, Peroxisome proliferation, Phospholipidosis, Photo-induced chromosome damage 

in vitro, Photoallergenicity, Photocarcinogenicity, Photogenotoxicity in vitro, Photogenotoxicity in vivo, 

Photomutagenicity in vitro, Phototoxicity, Pulmonary toxicity, Rapid prototypes: adrenal gland toxicity, 

Rapid prototypes: bladder disorders, Rapid prototypes: blood in urine, Rapid prototypes: bone marrow 

toxicity, Rapid prototypes: bradycardia, Rapid prototypes: cardiotoxicity, Rapid prototypes: chromosome 

damage in vitro, Rapid prototypes: hepatotoxicity, Rapid prototypes: kidney disorders, Rapid prototypes: 

mitochondrial dysfunction, Rapid prototypes: nephrotoxicity, Rapid prototypes: splenotoxicity, Rapid 

prototypes: testicular toxicity, Rapid prototypes: thyroid toxicity, Respiratory sensitisation, Skin 

sensitisation, Teratogenicity, Testicular toxicity, Thyroid toxicity, Uncoupler of oxidative phosphorylation

Superendpoints

Carcinogenicity (SUPER), Chromosome damage (SUPER), Genotoxicity (SUPER), Hepatotoxicity 

(SUPER), HERG channel inhibition (SUPER), Irritation (SUPER), Miscellaneous endpoints (SUPER), 

Mutagenicity (SUPER), Ocular toxicity (SUPER), Rapid prototypes: adrenal gland toxicity (SUPER), 

Rapid prototypes: bladder disorders (SUPER), Rapid prototypes: blood in urine (SUPER), Rapid 

prototypes: bone marrow toxicity (SUPER), Rapid prototypes: bradycardia (SUPER), Rapid prototypes: 

cardiotoxicity (SUPER), Rapid prototypes: chromosome damage in vitro (SUPER), Rapid prototypes: 

hepatotoxicity (SUPER), Rapid prototypes: kidney disorders (SUPER), Rapid prototypes: mitochondrial 

dysfunction (SUPER), Rapid prototypes: nephrotoxicity (SUPER), Rapid prototypes: splenotoxicity 

(SUPER), Rapid prototypes: testicular toxicity (SUPER), Rapid prototypes: thyroid toxicity (SUPER), 

Reproductive toxicity (SUPER), Respiratory sensitisation (SUPER), Skin sensitisation (SUPER), Thyroid 

toxicity (SUPER)
30

Constraints

Perceive tautomers true

Perceive mixtures true

Perceive alerts without rules false

Average molecular mass

76.09 (Lhasa Limited, version 1.0)

Exact molecular mass

76.0524 (Lhasa Limited, version 1.0)

Log Kp

-3.92 (Potts & Guy, version 1.0 (LogP: BioByte Corp., version 5.3; Average Molecular Mass: Lhasa 

Limited, version 1.0))

Log P

-1.04 (BioByte Corp., version 5.3)

Submitted compound

Predictions

Derek KB 2012 1.0

KnowledgeBase name

Derek KB 2012 1.0

KnowledgeBase version

1.0

KnowledgeBase last modified

29 November 2012 11:56:30

KnowledgeBase location

C:/Program Files/Lhasa Limited/Lhasa Knowledge Suite - Nexus 

1.5/KnowledgeBases/org.lhasalimited.pluto.knowledge.derek_1.0.7

KnowledgeBase certified by

Lhasa Limited, Leeds, Yorkshire, UK
31

Alerts found

RapidPrototype059 1,3-Dihydroxypropane or derivative. Rapid prototypes: nephrotoxicity in mammal

Reasoning summary

Rapid prototypes: nephrotoxicity in mammal is EQUIVOCAL

Reasoning summary and alerts found

Rapid prototypes: nephrotoxicity in mammal is EQUIVOCAL

RapidPrototype059 1,3-Dihydroxypropane or derivative

Alert overview: RapidPrototype059 1,3-Dihydroxypropane or derivative

Comments

This alert describes the nephrotoxicity of 1,3-dihydroxypropane and its derivatives. This is a rapid prototype alert 

derived using a proprietary data set of 731 chemicals, classified on the basis of the presence or absence of 

histopathologic lesions in the kidney in oral rat repeat dose studies mostly of 28-days duration. Eight chemicals in 

this data set activated this rapid prototype alert and five of these were nephrotoxic.

Locations

Reasoning details

Rapid prototypes: nephrotoxicity is EQUIVOCAL

The parameters that have influenced your prediction are: substructures in the input structure, which have a potential 

for rapid prototypes: nephrotoxicity, your selected species which is mammal.

Rule 266: If [species mammal] is [certain] then [Species dependent variable 8] is [equivocal]

species mammal is CERTAIN
32

Rule 995: If [Rapid prototypes: nephrotoxicity alert] is [certain] then [Rapid prototypes: nephrotoxicity] is [Species 

dependent variable 8]

Rapid prototypes: nephrotoxicity alert is CERTAIN

Species dependent variable 8 is EQUIVOCAL

Rule 266

If [species mammal] is [certain] then [Species dependent variable 8] is [equivocal]

Comments:

In mammals the variable "Species dependent variable 8" is equivocal.

References:

Rule 995

If [Rapid prototypes: nephrotoxicity alert] is [certain] then [Rapid prototypes: nephrotoxicity] is [Species dependent 

variable 8]

Comments:

If a chemical contains a rapid prototype alert for nephrotoxicity then it is considered equivocal that the chemical 

will cause nephrotoxicity in mammals and impossible in bacteria. The variation in rule outcome with species is 

achieved via use of the variable "Species dependent variable 8".

References:

Reasoning glossary:

Certain

There is proof that the proposition is true.

Probable

There is at least one strong argument that the proposition is true and there are no arguments against it.

Plausible

The weight of evidence supports the proposition.

Equivocal

There is an equal weight of evidence for and against the proposition.

Doubted

The weight of evidence opposes the proposition.

Improbable

There is at least one strong argument that the proposition is false and there are no arguments that it is true.

Impossible

There is proof that the proposition is false.

Open

There is no evidence that supports or opposes the proposition.

Contradicted

There is proof that the proposition is both true and false.