UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

 OFFICE OF CHEMICAL SAFETY 

 AND POLLUTION PREVENTION

December 16, 2013

MEMORANDUM

SUBJECT: Petition IN-10520; Dimethyl esters of glutaric acid, succinic acid, and adipic acid; Human 

Health Risk Assessment and Ecological Effects Assessment to Support Proposed Exemption from the 

Requirement of a Tolerance When Used as Inert Ingredients in Pesticide Formulations.

All PC Code: Dimethyl Glutarate: 800696

 Dimethyl Succinate: 877809

 Dimethyl Adipate: 800095

DP Barcode: 009295288

Regulatory Action: Inert 

Tolerance Exemption; 40 

CFR 180.910

Petition No: IN-10520 All CAS No:

1119-40-0, 

106-65-0, 

627-93-0

FROM: Deirdre Sunderland, Industrial Hygienist

Inert Ingredient Assessment Branch (IIAB)

Registration Division (7505P)

TO: PV Shah, Chief

Inert Ingredient Assessment Branch (IIAB)

Registration Division (7505P)
2

Table of Contents

Executive Summary............................................................................................................... 3

1.0 Background.................................................................................................................... 6

2.0 Inert Ingredient Profile....................................................................................................... 6

 2.1 Summary of Uses............................................................................................................ 6

 2.2 Physical and Chemical Properties......................................................................................... 7

 2.3 Metabolism and Pharmacokinetics....................................................................................... 9

3.0 Hazard Assessment........................................................................................................... 9

 3.1 Summary of Toxicity Data................................................................................................. 9

 3.2 Toxicity Profile.............................................................................................................. 9

 3.2.1 Acute Toxicity........................................................................................................... 9

 3.2.2 Dermal Absorption..................................................................................................... 12

 3.2.3 Subchronic Toxicity................................................................................................... 13

 3.2.4 Reproductive and Developmental Toxicity........................................................................ 18

 3.2.5 Neurotoxicity............................................................................................................ 21

 3.2.6 Mutagenicity............................................................................................................ 22

 3.2.7 Carcinogenic Potential................................................................................................ 22

 3.3 Endpoint Selection and Levels of Concern............................................................................. 22

 3.4 FQPA Safety Factor Considerations.................................................................................... 23

 

4.0 Exposure Assessment....................................................................................................... 24

 4.1 Dietary Exposure........................................................................................................... 24

 4.1.1 Acute Exposure......................................................................................................... 24

 4.1.2 Chronic Exposure...................................................................................................... 24

 4.1.3 Cancer................................................................................................................... 26

 4.2 Residential Exposure...................................................................................................... 26

 4.3 Occupational Exposure................................................................................................... 27

5.0 Aggregate Risk and Determination of Safety........................................................................... 27

5.1 Acute Dietary Risk.......................................................................................................... 27

5.2 Chronic Dietary Risk....................................................................................................... 28

5.3 Cancer Risk for U.S. Population.......................................................................................... 28

5.4 Short-term/Intermediate Aggregate Risk................................................................................ 28

6.0 Cumulative Risk............................................................................................................. 28

7.0 Environmental Fate......................................................................................................... 29

8.0 Ecological Effects........................................................................................................... 29

8.1 Acute Fish Toxicity......................................................................................................... 29

8.2 Acute Invertebrate Toxicity............................................................................................... 30

8.3 Acute Algal Toxicity....................................................................................................... 30

9.0 Risk Characterization....................................................................................................... 31
3

EXECUTIVE SUMMARY

On October 11, 2012, SciReg, Inc., on behalf of Rhodia Inc., submitted a petition to the Environmental 

Protection Agency, herein referred to as the agency or EPA, to amend 40 CFR 180.910 by establishing 

an exemption from the requirement of a tolerance for the use of the inert ingredients dimethyl esters of 

glutaric acid (i.e., dimethyl glutarate (DMG), CAS Reg. No. 1119-40-0), succinic acid (i.e., dimethyl 

succinate (DMG), CAS Reg. No. 106-65-0), and adipic acid (i.e., dimethyl adipate (DMA), CAS Reg. 

No. 627-93-0) (collectively referred to as DMEGSA for ease of reading) for use as solvents/co-solvents 

in pesticide formulations applied to growing crops and raw agricultural commodities after harvest. 

These three discrete compounds are short, straight-chain dicarboxylic acid dimethyl esters differing by 

one carbon atom, from four to six carbons, in the dicarboxylic acid moiety. They are used as solvents, 

plasticizers, polymer intermediates, and as components in paint strippers, polishes, and lacquer thinners. 

A mixture of the three, known as dibasic esters (DBE) represented by CAS Reg. No. 95481-62-2, is

also approved for use as inert ingredients under 40 CFR 180.1277. DMEGSA are similar in structure, 

physicochemical properties and toxicity responses among the category members. The three category 

members (i.e., DMG, DMS, and DMA) and a mixture of the three (e.g., DBE) produce similar levels of 

acute and repeated-dose toxicity in experimental animals, such that information on one category member 

is expected to represent the toxicity of the category as a whole. 

DMEGSA is hydrolyzed to its corresponding monomethyl esters and subsequent dicarboxylic acid 

metabolites (i.e., adipic, glutaric, and succinic acid) by carboxylesterases. Based on the expected 

similarity in toxicity and fate, this risk assessment relies upon available data for DBE, DMG, DMA, and 

DMS. In addition, the toxicological properties of their metabolites were also considered (qualitatively) 

and presented here to address potential exposure via the oral route.

Acute toxicity studies conducted with DMEGSA demonstrate low acute oral and dermal toxicity. 

DMEGSA showed minimal eye irritation, no dermal irritation, and no dermal sensitization. In addition 

to a 14-day dermal study, two oral rat studies have been conducted on DBE- a 14-day and a one month 

study. Animals in the 14-day study showed reduced weight gain and food consumption at 1,684 

mg/kg/day but showed no adverse effect at 842 mg/kg/day. Animals in the one month study showed no 

adverse effects at the limit dose of 1,000 mg/kg/day. In the dermal study mild skin irritation was noted; 

however, these effects were reversible and no systemic effects were observed at any dose tested up to 

the limit dose of 1,000 mg/kg/day. 

Oral studies on the metabolites were also used to support a safety finding for DMEGSA. Available 

repeat dose oral studies on the metabolites include a 13-week study on succinic acid, two 90-day studies 

on glutaric acid and a two year study on adipic acid. Succinic acid was shown to cause decreased body 

weight gain in rats at and above 2,500 mg/kg/day. Glutaric acid also caused a decrease in body weight 

gain in both rats and dogs at 1,000 and 750 mg/kg/day, respectively. Similarly, adipic acid was seen to 

cause decreased body weight gain and food consumption in rats at 2,250 mg/kg/day. The results of 

these studies indicate that the metabolites of DMEGSA are of low toxicity via the oral route of 

exposure. 

The majority of the repeat dose studies conducted on DBE and/or DMEGSA are via the inhalation route 

of exposure. The available database includes three 90-day inhalation studies. In the first study dose 
4

dependant degeneration of the olfactory epithelium was observed at and above 0.05 mg/L. Exposed 

animals also showed microscopic alterations in the liver (males) and lung (females) and hormonal 

changes in both sex. The significance of these findings is unclear because the decrease in male hormone 

levels should result in a decrease in sperm counts, yet the opposite effect was observed. The single study 

showing changes in estradiol was not observed in the other two studies. Furthermore, there were no 

functional parameters such as estrous cycle and sperm motility or morphology affected. A reproductive 

study was conducted with DBE and there were no effects on fertility, viability of pups at birth, and the 

ability of the mothers to lactate.

Two other 90-day rat studies tested DBE and again, degeneration of the olfactory epithelium was noted 

at all doses tested (0.02-1.0 mg/L). In both studies decreases in liver weight were observed but no 

histopathological findings were evident. At high doses slight increases in relative heart and testes 

weights in males and a slight decrease in absolute spleen weight in females were observed. These slight 

organ weight changes were not accompanied by any histopathological changes and are therefore,

considered to be of minimal biological significance. No other significant effects were observed. 

Like much of the repeat dose testing, inhalation was also the route of exposure used in the reproductive 

and developmental studies. Depressed pup weights were observed in a one-generation reproduction 

inhalation toxicity study with DBE at 1.0 mg/L but were only seen in the presence of maternal toxicity. 

In two developmental inhalation studies no developmental effects were observed. Similarly, no adverse 

developmental effects were observed in oral studies on the metabolites glutaric acid and adipic acid at 

doses up to and including 1,300 mg/kg/day.

Repeat dose inhalation studies have demonstrated the chemicals potential to affect the olfactory mucosa 

in the nasal passage of rats. These local effects are believed to be related to the hydrolysis of DMEGSA 

by carboxylesterases located in the nasal/olfactory epithelium to their dicarboxylic acid metabolites. The

effects on the olfactory epithelium are expected to be of much lower impact in humans due to major 

physiological differences between rats and humans.

No neuropathological changes or effects on the functional observation battery parameters were reported 

in any of the studies. The agency does not believe DMEGSA will be neurotoxic. Based on study results 

DMEGSA is not expected to be mutagenic or genotoxic. Chronic/carcinogenicity studies could not be

identified for DMEGSA. A DEREK evaluation for DMG and DMS was conducted and did not show any

special alerts. In addition, carcinogenicity studies were conducted with adipic acid and monosodium 

succinate in rats and no carcinogenic effects were observed. Therefore, the agency does not expect 

DMEGSA to be carcinogenic in humans. 

Repeated exposures to DMEGSA via inhalation show local effects (likely a result of irritation at the 

point of contact in the nasal region) as well as some changes in hormone levels that, although 

consistently observed, are not considered to be toxicologically significant. The point of departure for the 

risk assessment for chronic oral routes of exposure was from the 14-day oral toxicity study in rats. The

no observed adverse effect level (NOAEL) was 842 mg/kg/day and the lowest observed adverse effect 

level (LOAEL) was 1684 mg/kg/day based on reduced weight gain and food consumption. A 1000 fold 

uncertainty factor was used for chronic exposure (10X interspecies extrapolation, 10X for intraspecies 

variability and 10X FQPA safety factor). 
5

Exposure to DMEGSA will be primarily through the oral route from consuming food treated with 

pesticide products containing the chemical. EPA’s highly conservative I-DEEM model was used to 

estimate oral exposure. I-DEEM showed the exposure from the use of this inert ingredient in pesticide 

formulations (including exposure through drinking water) would result in acceptable risk to all 

subpopulations. The most highly exposed subpopulation was children 1-2 years old at 83.9% of the 

cPAD (chronic Population Adjusted Dose).

Residential exposure to outdoor pesticide products was evaluated using agency approved models to 

estimate the risk of residential post-application exposure to treated lawns. All exposure scenarios 

resulted in acceptable levels of risk to all subpopulations evaluated. Exposure to DMEGSA inert 

ingredients via paint, residential antimicrobials, and pet products were not evaluated in this risk 

assessment. When oral residential and dietary exposures were combined exposure did not exceed the 

acceptable level of risk. 

Similarly, occupational exposure would be expected via the dermal and inhalation routes of exposure; 

however, because no endpoints of concern were identified for these routes of exposure, a qualitative 

occupational assessment was conducted. 

Based on ecological (i.e., fish, invertebrates, and algae) and fate studies the agency concluded that

DMEGSA does not pose an ecological risk to terrestrial or aquatic species. DMEGSA is not expected to 

persist in the environment and the potential for bioaccumulation is low. 

In assessing an inert ingredient for use in pesticide products the agency takes into account all available 

information regarding the toxicity, fate, and use of the inert ingredient. In the case of DMEGSA many of 

the studies showed olfactory effects in rats following inhalation exposure. While these effects were 

observed in rats, it is unlikely that the same effects will be seen in humans due to physiological and 

chemical differences between the species. In addition, some studies showed hormonal changes which 

were not replicated in other studies and organ effects were most often not accompanied by histological 

changes. The implications of these effects are unknown but due to their use in food products and the low 

toxicity observed in oral and dermal studies coupled with the expected exposure from the use of these 

chemicals as inert ingredients in pesticide products, EPA concludes that there is a reasonable certainty 

that no harm will result to the general population, including infants and children, from aggregate 

exposure to residues of DMEGSA when used as an inert ingredients in pesticide formulations under 40 

CFR 180.910.
6

1.0 BACKGROUND

On October 11, 2012, SciReg, Inc., on behalf of Rhodia Inc., submitted a petition to the Environmental 

Protection Agency, herein referred to as the agency or EPA, to amend 40 CFR 180.910 by establishing 

an exemption from the requirement of a tolerance for the use of the inert ingredients dimethyl esters of 

glutaric acid (i.e., dimethyl glutarate, CAS Reg. No. 1119-40-0), succinic acid (i.e., dimethyl succinate, 

CAS Reg. No. 106-65-0), and adipic acid (i.e., dimethyl adipate, CAS Reg. No. 627-93-0) for use as 

solvents/co-solvents in pesticide formulations applied to growing crops and raw agricultural 

commodities after harvest. 

Throughout this document various names/acronyms are used to describe dimethyl glutarate (DMG), 

dimethyl adipate (DMA), and dimethyl succinate (DMS). As a point of clarification, dimethyl esters of 

glutaric acid, succinic acid, and adipic acid (DMEGSA) is used to collectively refer to the these

individual chemicals whereas dibasic esters (DBE), CAS Reg. No. 95481-62-2, is a chemical mixture of 

approximately 55-75% dimethyl glutarate, 15-27% dimethyl succinate, and 10-25% dimethyl adipate.

In 2008 the EPA published a “Screening-Level Hazard Characterization: Dibasic Esters (DBE) 

Category” document that outlined EPAs determination that information on one of the individual 

components of DBE or DBE itself would be representative of this group and subsequently can be used 

as surrogate or read across data for all members of the group:

The basis for the category is similarity in structure, physicochemical properties and toxicity 

responses among the category members. The three discrete compounds are short, straight-chain 

dicarboxylic acid dimethyl esters differing by one carbon atom, from four to six carbons, in the 

dicarboxylic acid moiety. The three category members and the mixture produce similar levels of 

acute and repeated-dose toxicity in experimental animals, such that information on one category 

member is expected to represent the toxicity of the category as a whole.

This 2008 document also associates this chemical category to the metabolites of DMEGSA “...this 

category is related to another, similar category called the dicarboxylic acids (which consists of succinic 

acid, glutaric acid and adipic acid).”

Based on the expected similarity in toxicity and fate, this risk assessment relies upon available data for 

DBE, DMG, DMA, and DMS. In addition, the toxicological properties of their metabolites were also 

considered (qualitatively) and presented here to support the toxicological profile of DMEGSA, in 

particular to address the potential exposure via the oral route.

To access the Office of Chemical Safety and Pollution Prevention (OCSPP) test guidelines referenced in 

this document electronically, please go to http://www.epa.gov/ocspp and select “Test Methods and 

Guidelines.”

2.0 INERT INGREDIENT PROFILE

2.1 Summary of Uses
7

Dibasic esters are used as solvents, plasticizers, polymer intermediates, and as components in paint

strippers, polishes, and lacquer thinners. In addition, dimethyl succinate (DMS) has been approved by 

the US Food and Drug Administration (FDA) as a direct food additive under 21 CFR 172.515 as a 

synthetic flavoring agent and adjuvant. DBE is currently exempt from the requirement of tolerance as an 

inert ingredient under 40 CFR 180.1277 when used as a solvent and/or anti-freeze at 10% w/w or less in 

microencapsulated pesticide formulations with the active ingredient cyfluthrin. 

Metabolites of DBE are naturally occurring dicarboxylic acids: succinic, glutaric, and adipic acids.

Adipic acid, for example, can be found in edible plant parts such as beet, ripe fruits of Morinda citrifolia, 

and rice straw. (OECD, 2006) Adipic and succinic acids are classified as Generally Recognized As Safe 

(GRAS) by the U.S. Food and Drug Administration (FDA) for substances directly added to human food 

(21 CFR 184.1009 and 21 CFR 582.1009, and 21 CFR 184.1091 and 21 CFR 582.1091, respectively). 

Methanol, a metabolite of DMEGSA, is an approved food use inert ingredient in pesticide formulations 

under 40 CFR Part 180.910 and 180.920 as a solvent and 180.930 as a solvent/co-solvent.

2.2 Physical and Chemical Properties

Some of the physical and chemical characteristics of dimethyl adipate, dimethyl glutarate, and dimethyl 

succinate along with their structure and nomenclature, are found in the tables below. 

Table 1. Physical and Chemical Properties of Dimethyl Adipate

Parameter Value Reference

Structure

 

ChemIDPlus, 2013

CAS # 627-93-0 ChemIDPlus 2013

Molecular Formula C8-H14-O4 ChemIDPlus 2013

Molecular Weight 174

Common Names Hexanedioc acid, dimethyl ester; dimethyl 

hexanedioate; adipic acid, dimethyl ester ChemIDPlus, 2013 

Melting Point 8.5°C SOCMA 2002*

Boiling Point 230.9°C SOCMA 2002*

Density 1.062 g/cm3 SOCMA 2002*

Vapor Pressure 0.47 Pa @ 25 oC (4 x10-3 mm Hg) MRID 48968810; 

OSCPP 830.7950

Log Kow 1.4 @ 22 oC MRID 48968808, 

OSCPP 830.7550

Water Solubility 4.0 g/L @ 20oC MRID 48968809; 

OSCPP 830.7840

Henry's Law Constant 2.31 x 10-6 atm-m3

/mole @ 25oC ; 9.77 x 10-7

atm-m3/mole 

ChemIDPlus 2013; HSDB 

2013

*Referenced in EPA’s 2008 “Decision Document for Petition #5E4442; Dibasic Esters (DBE; CAS Reg. No. 95481-62-2)”. 

The source of the information is the Synthetic Organic Chemical Manufacturers Association Dibasic Esters Group (SOCMA 

DBE Group) who submitted data on DBE and its components as part of the TSCA Section 4 Enforceable Consent Agreement 

with the EPA initiated on August 8, 1999. 
8

Table 2. Physical and Chemical Properties of Dimethyl Glutarate

Parameter Value Reference

Structure ChemIDPlus 2013

CAS # 1119-40-0 ChemIDPlus 2013

Molecular Formula C7-H12-O4 ChemIDPlus 2013

Molecular Weight 160 SOCMA 2002*

Common Names

Dimethyl glutarate; dimethyl pentanedioate;

glutaric acid, dimethyl ester; pentanedioic 

acid, dimethyl ester

ChemIDPlus, 2013

Melting Point -37 °C SOCMA 2002*

Boiling Point 213.5-214°C SOCMA 2002*

Density 1.0876 g/cm3 @ 20oC SOCMA 2002*

Vapor Pressure 8.5 Pa @ 25oC (6.4 x10-2 mm Hg) MRID 48968810; 

OSCPP 830.7950

Log Kow 1.0 @ 22oC MRID 48968808; 

OSCPP 830.7550

Water Solubility 40.5 g/L @ 20oC MRID 48968809; 

OSCPP 830.7840

Henry's Law Constant 6.43 x 10-7 atm-m3/mole @ 25oC ChemIDPlus 2013

*Referenced in EPA’s 2008 “Decision Document for Petition #5E4442; Dibasic Esters (DBE; CAS Reg. No. 95481-62-2)”. 

The source of the information is the Synthetic Organic Chemical Manufacturers Association Dibasic Esters Group (SOCMA 

DBE Group) who submitted data on DBE and its components as part of the TSCA Section 4 Enforceable Consent Agreement 

with the EPA initiated on August 8, 1999. 

Table 3. Physical and Chemical Properties of Dimethyl Succinate

Parameter Parameter Reference

Structure ChemIDPlus 2013

CAS # 106-65-0 ChemIDPlus 2013

Molecular Formula C6-H10-O4 ChemIDPlus 2013

Molecular Weight 146 SOCMA 2002*

Common Names Dimethyl succinate; dimethyl butanedioate; 

butanedioic acid, dimethyl ester

ChemIDPlus 2013

Melting Point 19°C SOCMA 2002*

Boiling Point 196°C SOCMA 2002*

Density 1.11 g/cm3 @ 25°C SOCMA 2002*

Vapor Pressure 9.4 Pa @ 25°C (7.1 x 10-2 mm Hg) MRID 48968810; 

OSCPP 830.7950

Log Kow 0.6 @ 22°C MRID 48968808; 

OSCPP 830.7550

Water Solubility 26.0 g/L @ 20 oC MRID 48968809; 

OSCPP 830.7840
9

Table 3. Physical and Chemical Properties of Dimethyl Succinate

Parameter Parameter Reference

Henry's Law Constant 6.4 x 10-8 atm-m3/mole @ 25°C ChemIDPlus 2013, HSBD 

2013

*Referenced in EPA’s 2008 “Decision Document for Petition #5E4442; Dibasic Esters (DBE; CAS Reg. No. 95481-62-2)”. 

The source of the information is the Synthetic Organic Chemical Manufacturers Association Dibasic Esters Group (SOCMA 

DBE Group) who submitted data on DBE and its components as part of the TSCA Section 4 Enforceable Consent Agreement 

with the EPA initiated on August 8, 1999.

2.3 Metabolism and Pharmacokinetics

Various studies have shown that DBE undergoes carboxylesterase-mediated hydrolysis in rodent nasal 

mucosa to form monomethyl esters (i.e., monomethyl glutarate, monomethyl succinate, and monomethyl

adipate), and subsequently dicarboxylic acids (i.e., glutaric acid, succinic acid, and adipic acid) and 

methanol (Trela, 1991; US CPSC, 1994). Mammalian carboxylesterases are localized in the 

endoplasmic reticulum of many tissues (e.g., liver, kidney, brain, testis, gastrointestinal tract, etc.), with 

the highest levels of activity found in the liver of many species. (MRID 48968830; 48968831) Although 

different areas of the body may be more efficient at metabolizing DBEs, following oral exposure, 

dimethyl esters are expected to be metabolized by carboxylesterase in the body similar to those seen in 

rodent nasal mucosa studies following inhalation exposure. 

3.0 HAZARD ASSESSMENT

3.1 Summary of Toxicity Data

This risk assessment relies upon available data for the individual components dimethyl glutarate (DMG), dimethyl 

adipate (DMA), and dimethyl succinate (DMS) as well as studies on dibasic esters (DBE) under CAS 

Reg. No. 95481-62-2 and a mixture of DMEGSA chemicals similar in composition to DBE. In addition, 

data on the dicarboxylic acids metabolites glutaric acid, succinic acid (as monosodium succinate), and 

adipic acid are used to support the toxicological profile of DMEGSA. See Table 4 for a summary of the 

acute toxicity profile, Table 5 for repeat dose studies (including reproductive and developmental), and 

Table 6 for studies on DMEGSA metabolites. 

3.2 Toxicity Profile

3.2.1 Acute Toxicity

Acute Oral Toxicity

Sprague-Dawley rats (5/sex/dose) were administered DMS via gavage at 500 and 5000 mg/kg and 

observed for 14 days. No mortalities occurred at 500 mg/kg and all animals died at 5000 mg/kg. (EPA, 

2008b)

LD50 > 500 and < 5000 mg/kg

Sprague-Dawley rats (5/sex/dose) were administered DMG via gavage at 5000 mg/kg and observed for 

14 days. All animals survived to 14 days. (EPA, 2008b)

LD50 > 5000 mg/kg
10

Sprague-Dawley rats (5/sex/dose) were administered DMA via gavage at 500 and 5000 mg/kg and 

observed for 14 days. No mortalities occurred at 500 mg/kg and two animals died at 5000 mg/kg. (EPA, 

2008b)

LD50 > 5000 mg/kg

Sprague-Dawley Crl:CD (SD) BR rats (5/sex) were administered a single oral dose of 2,000 mg/kg of a 

test substance comprised of a mixture of DMG, DMS, and DMA (OSCPP 870.1100) . No mortality or 

clinical signs were observed during the 14 day observation period. All animals were euthanized and 

necropsied at the end of the study. At necropsy, a macroscopic examination revealed no abnormalities. 

(MRID 48968813)

LD50 >2,000 mg/kg

Acute Dermal Toxicity

New Zealand White rabbits (5/sex/chemical) were administered a single dose (5000 mg/kg) of either 

DMS, DMA, or DMG, applied directly to the skin for 24 hours and were observed for 14 days after 

removal of excess test substance. No mortalities occurred. (EPA, 2008b)

LD50 > 5000 mg/kg

New Zealand White rabbits (5/sex) were administered a single dose (5000 mg/kg) of DBE applied 

directly to the skin for 24 hours and were observed for 14 days after removal of excess test substance. 

No mortalities occurred. (EPA, 2008b)

LD50 > 5000 mg/kg

Sprague Dawley rats (5/sex) were administered a single dermal dose of 2,000 mg/kg of a test substance 

comprised of a mixture of DMG, DMS, and DMA applied to a clipped area skin (5 x 7 cm) for 24 hours 

under a semi-occlusive dressing (OSCPP 870.1200). Examinations for mortality, clinical signs, and 

body weight gain were performed during the 14-day study period. No deaths occurred and no clinical 

signs were observed during the observation period. All surviving animals were euthanized and 

necropsied at the end of the observation period. Macroscopic examination revealed no abnormalities. 

(MRID 48968814)

LD50 > 2,000 mg/kg 

Acute Inhalation Toxicity

Crl:CD rats (5/sex/dose) were exposed nose-only for a single 4-hour period to aerosol/vapor mixtures of 

DBE in air at 5.6 and 11 mg/L and observed for 14 days. Transient clinical signs observed at 

concentrations of 5.6 mg/L or greater include red ocular or nasal discharge, lethargy, labored breathing 

or hunched posture, and slight to severe weight loss. Ophthalmologic examination revealed mild

chemosis (swelling) in the bulbar conjunctiva. No mortalities occurred. (EPA, 2008b)

LD50 > 11 mg/L

Primary Eye Irritation

A test substance comprised of a mixture of DMG, DMS, and DMA was tested for acute ocular irritation 

by applying a single dose of 0.1 mL, into the conjunctival sac of three male New Zealand White rabbits

(OSCPP 870.2400). One eye remained untreated and served as a control. The eyes were not rinsed. 

Ocular examinations were performed at 1, 24, 48, and 72 hours after instillation. The interpretation of 

the results was based on Kay and Calandra’s modified scale. 
11

A slight corneal opacity (score 1) was observed 24 hours after instillation in one of the three animals. No 

iritis was observed throughout the observation period in any of the animals. Conjunctival redness was 

observed at 1 hour in all animals (score 2 or 3), and in two animals 24 hours after instillation (score 1). 

Chemosis (score 1 or 3) was observed in two of three animals at 1 hour after instillation. In addition,

discharge was noted at 1 hour for all animals. All effects cleared by 48 hours post instillation. Based on 

the results of this study DME is considered mildly irritating. (MRID 48968815)

According to the EPA’s previous assessments (EPA, 2008a; EPA, 2008b) when tested individually or in 

a mixture, that these chemicals cause mild to moderate eye irritation. All effects cleared by Day 7 of 

observation. 

Primary Dermal Irritation

1) DMA, DMG, and DMS were individually administered to New Zealand White rabbits 

(3/sex/chemical) as a single dose applied directly to two 1 x 1 inch areas of skin on the back and held in 

place with semi-occlusive dressings for 4 hours. Animals were observed for subsequent 3 days and 

treated areas were observed at 30 minutes and 24, 48, and 72 hours. No dermal irritation was observed 

for DMA, DMG, or DMS. (EPA, 2008b)

2) A test substance comprised of a mixture of DMG, DMS, and DMA was tested for acute skin irritation 

when a single dermal dose of 0.5 mL was applied to a clipped area of the skin (6 cm2

) of three male 

New Zealand White rabbits for four hours (OSCPP 870.2500). Cutaneous examinations were performed 

at 1, 24, 48, and 72 hours after removal of dressing. No cutaneous reactions were observed in any of the 

animals, throughout the observation period. (MRID 48968816)

The mixture was not considered a skin irritant.

NOTE: According to the Agency’s 2008 “Decision Document for Petition #5E4442; Dibasic Esters 

(DBE; CAS Reg. No. 95481-62-2)” 

Dermal irritation from DBE exposure varies depending on duration of exposure. For example, in the

dermal Irritation study in rabbits submitted by the petitioner (Sarver 1989), 24 hours of exposure to

DBE caused mild to moderate irritation at 24 and 48 hours post exposure. One rabbit had slight

edema and severe erythema at 72 hours, but no edema and no moderate to mild erythema were

observed in the remaining rabbits. In other rabbit dermal irritation studies, four hours exposure to

DBE or its components DMA, DMG and DMS were considered non- irritating to rabbits (SOCMA

2002). DBE was also found to be non-irritating to the skin of guinea pigs, however the duration of

exposure was not provided (SOCMA 2002). DBE was also not considered to be a skin-sensitizer in

guinea pigs.

Dermal Sensitization

A test substance comprised of a mixture of DMG, DMS, and DMA was assessed for dermal 

sensitization in female CBA/CaOlaHsd mice, using the Local Lymph Node Assay (OSCPP 870.2600). 

A preliminary test was conducted in two mice with the selected concentrations of 10, 25, and 50% (w/v) 

and 100% (undiluted) to assess potential local irritation. After 24 hours, no irritating effects were 

observed at these concentrations following a single application. In the main assay, five treated groups of 

four animals each received the test item to the dorsum of each ear lobe for three consecutive days at
12

concentrations of 5, 10, 25, or 50% (w/v) in the vehicle acetone/olive oil (4/1, v/v), or 100% (undiluted). 

In addition, a control group of four animals received the vehicle alone. 

No clinical signs were observed in any animals of the control group, Group 2 (5%), Group 3 (10%) or 

Group 4 (25%). On the second application day, a slight to moderate ear erythema was observed at both 

dosing sites in all mice of Group 5 (50%) and Group 6 (100%, undiluted), persisting for a total of two 

days. (MRID 48968817) Based on the results of this study, the mixture was not considered to be a 

dermal sensitizer.

Table 4. Summary of Acute Toxicity Data

Endpoint DMS DMG DMA DMA, DMG, 

and DMS 

Mixture

Toxicity 

Category

Acute Oral 

LD50 (mg/kg)

>500 and 

<5000

>5000 >5000 > 2000 and 

>5000

III-IV

Acute Dermal 

LD50 (mg/kg)

>5000 >5000 >5000 > 2000 and 

>5000

III-IV

Acute 

Inhalation LD50

(mg/L)

No Data No Data No Data >11 IV

Skin Irritation 

(4 hour 

exposure)

Not a skin 

irritant 

Not a skin 

irritant

Not a skin 

irritant

Not a skin 

irritant

IV

Eye Irritation Mild to 

moderate

Mild to 

moderate

Moderate Mild to 

moderate

III

3.2.2 Dermal Absorption

An in vitro OECD 428 study on the individual DBE homologues, DMS, DMG, and DMA, and for the 

homologues in a 1:3:1 (DMS:DMG:DMA) blend examined the dermal kinetic parameters of penetration 

rate, lag time, and permeability coefficient (Kp) for rat (males of the Sprague-Dawley strain, 

Crl:CD®(SD)IGS BR) and human skin. 

An infinite dose (150 μL) of the test solvent was applied to the epidermal surface of six skin replicates 

per species. Under occlusive conditions, receptor chamber effluent samples were collected hourly for 

each replicate until six hours postapplication. Following application of the individual dibasic ester 

homologues the penetration rates for each homologue were comparable within a species and ranged 

from 3,131.8 to 4,542.4 μg/cm2

/h for rat skin and from 79.5 to 113.0 μg/cm2/h for human skin. In 

contrast, when the DBE blend containing DMS, DMG, and DMA was applied to rat skin, the penetration 

rate for DMS (571.7 μg/cm2/h), DMG (1,571 μg/cm2/h), and DMA (507.0 μg/cm2/h) was slower 

compared to the penetration rates observed when the individual homologues were applied alone as a 

single solvent system. The permeability coefficients (Kp) were comparable for each homologue within a 

species and higher for rat skin compared to human skin. The Kp values for rat and human skin ranged 

from 2.12 x 10-3 to 4.18 x 10-3 cm/h and from 6.81 x 10-5 to 1.69 x 10-4, respectively. (Fasano, 2003)
13

3.2.3 Subchronic Toxicity 

Table 5. Summary of Toxicological Endpoints for DMEGSA Inert Ingredients for Use in 

Human Health Risk Assessments

Study Test Substance Toxicological Effect Reference

14-Day Oral

(Rat) DBE

NOAEL= 842 mg/kg/day

LOAEL= 1,684 mg/kg/day; reduced weight gain and 

food consumption

MRID 45740506

1-Month Oral

(Rat) DBE

NOAEL= 1,000 mg/kg/day (Highest Dose Tested 

(HDT))

LOAEL not established

EPA, 2008b

14-Day Dermal

(Rat)

DBE, DMA, 

DMG, DMS

Systemic NOAEL= 1,000 mg/kg/day (HDT)

Systemic LOAEL not established

Kirkpatrick, 

2000

90-Day Inhalation

(Rat)

DMS

NOAEL not established

LOAEL=0.4 mg/L; effects on nasal tissue, decreases 

in estradiol concentration in females and increased 

epididymal sperm count in males.

Bamberg, 2000 DMG

NOAEL= 0.01 mg/L

LOAEL= 0.05 mg/L; effects on nasal tissue, 

decreased serum LH and testosterone concentrations, 

increased epididymal sperm counts.

DMA

NOAEL not established

LOAEL= 0.4 mg/L; effects on nasal tissue, increased 

CP in liver, lungs, and nose.

90-Day Inhalation

(Rat) DBE NOAEL not establishedLOAEL= 0.16 mg/L; effects on nasal tissue MRID 45740503

90-Day Inhalation

(Rat) DBE NOAEL not establishedLOAEL= 0.02 mg/L; effects on nasal tissue MRID 48968819

Reproductive and 

Developmental 

Inhalation

(Rat)

DBE

Maternal NOAEL= 0.4 mg/L

Maternal LOAEL= 1 mg/L; depressed body weight

Reproductive NOAEL= 0.4 mg/L

Reproductive LOAEL= 1 mg/L; depressed pup weight

Developmental NOAEL= 1 mg/L (HDT)

Developmental LOAEL not established

MRID 48968822

Developmental 

Inhalation

(Rat)

DMG

Maternal NOAEL= 0.1 mg/L

Maternal LOAEL= 0.3 mg/L; body weight gains and 

clinical observations

Developmental NOAEL= 1 mg/L (HDT)

Developmental LOAEL not established

Munley, 2003

Developmental 

Inhalation

(Rat)

DBE

Maternal NOAEL= 0.16 mg/L

Maternal LOAEL= 0.4 mg/L; food consumption and 

body weight gain

Developmental NOAEL= 1 mg/L

Developmental LOAEL not established

MRID 48968820

ORAL

(DBE) 14-Day (rat) Oral 

DBE was tested in a 14-day oral toxicity study on Crl:CD male rats fed concentrations of 10,000, 

20,000, or 50,000 ppm (~842, 1684, or 4,210 mg/kg/day) in the diet. Daily weights and clinical 

observations were recorded. On the 14th test day, half of the rats of each test group were sacrificed. The 

remaining half was maintained on the regular diet for 14-days (recovery group). The animals in the 

recovery group were weighed every other day, observed for a 14-day recovery period, and sacrificed 14 
14

days later. All rats were examined grossly, selected tissues were weighed, and selected tissues and 

organs evaluated histologically.

No gross or microscopic pathologic changes that could be attributed to exposure of DBE were detected. 

No deaths were observed. No clinical signs other than initial and sporadic weight loss were seen. The 

rate of body weight gain was reduced in rats of the mid- and high-dose groups with lower food intake

also seen by these rats. During the recovery period, test rats in these two groups gained slightly more 

weight than the controls although the high-dose rats (4,210 mg/kg/day) weighed approximately 7% less 

at the end of the recovery period. (MRID 45740506)

No observed adverse effect level (NOAEL) = 842 mg/kg/day 

Lowest observed adverse effect level (LOAEL) = 1684 mg/kg/day based on reduced weight gain and 

food consumption. 

(DBE) 1 month (rat) Oral

In an oral gavage toxicity study, male and female Sprague-Daley rats were dosed with DBE daily at 0, 

100, 300 or 1000 mg/kg/day for 1 month. Clinical observations included mortality, body weights, food 

consumption, and clinicopathological measurements. Except for a small decrease in urine pH (not 

statistically significant) in male and female rats at 1000 mg/kg/day, no other systemic toxicity was 

evident. (EPA, 2008b)

NOAEL = 1000 mg/kg/day (highest dose tested)

LOAEL not established

Studies on metabolites (oral) - See Table 6

(Succinic acid) 13 week (rat) Oral

In a 13-week study, groups of male and female F344 rats were administered succinic acid (as 

monosodium succinate) at 0, 0.3, 0.6, 1.25, 2.5, 5 and 10% (approximately 0, 300, 600, 1250, 2500, 

5000 and 10,000 mg/kg/day) in their drinking water. All animals in the 10% group were severely 

emaciated and died within the first 4 weeks. The decreased body weight gain was also seen at and above 

2.5%. No effects were seen on hematological or biochemical parameters. Although atrophy of organs 

was observed, no treatment-related histological lesions were seen in any organ. (EPA, 2008c)

NOAEL = 1.25% (~1250 mg/kg/day)

LOAEL = 2.5% (~2500 mg/kg/day); based on decreased body weight gain

(Glutaric acid) 90 day (rat) Oral

Groups of male and female Sprague-Dawley rats were fed glutaric acid at 0, 0.5, 1.0 and 2.0% 

(approximately 0, 250, 500 and 1000 mg/kg/day) for 90 days. Body weight gain was markedly 

decreased in the 2% group in both sexes. No effects were seen on food consumption, hematology, 

clinical chemistry, urinalysis, absolute or relative organ weights or histopathology. No difference 

between control and treatment groups was observed in absolute or relative testes and ovary weights. 

Histopathological examination of testes, seminal vesicles, ovaries and uteri did not reveal any treatmentrelated effects. (EPA, 2008c)

NOAEL = 1% (~500 mg/kg/day)

LOAEL = 2% (~1000 mg/kg/day); based on decreased body weight gain
15

(Glutaric acid) 90 day (dog) Oral

In a 90-day study, groups of male and female Beagle dogs were fed diets containing 0, 1, 3 and 5% 

glutaric acid for days 1 – 10 and 0.5, 1, and 2% glutaric acid for days 11 – 90. Body weight loss was 

seen in male and females in the 5% group and in females of the 3% group after 10 days. The dogs in the 

high-dose group did not gain weight during the study whereas the body weight gain for all other animals 

was comparable to the control group. No changes to other parameters, including histology of testes or 

ovaries, were noted. (EPA, 2008c)

NOAEL = 2% (~500 mg/kg/day)

LOAEL = 3% (~750 mg/kg/day); based on decreased body weight gain

(Adipic acid) 2 year (rat) Oral

In a 2-year chronic feeding study, male and female Carworth Farms rats were fed diets containing 0, 0.1, 

1.0, 3.0 and 5.0% (males) or 0 and 1% (females) adipic acid (approximately 0, 75, 750, 2250, and 3750 

mg/kg/day, respectively). In males, body weight gain was suppressed in the 3 and 5% dose groups and 

there was a slight but consistent reduction in food consumption in the 5% exposure group. Wheezing, 

bloody crust about eyes and nose and body sores were noted in all groups (including control animals). 

There was a lower incidence of signs indicative of respiratory infection and body sores in animals from 

the 5% exposure group. No marked differences between control and treated groups were noted in organ 

weights or microscopic examination. In females, body weight gain and food consumption were not 

affected by treatment. (Horn, 1957)

NOAEL = 1% (~750 mg/kg/day)

LOAEL = 3% (~2250 mg/kg/day), based on decreased body weight gains and food consumption in 

males)

DERMAL 

(DBE, DMA, DMG, DMS) 14-Day (rat) Dermal 

Undiluted DBE, DMA, DMG, or DMS was applied to the shaved intact dorsal skin of rats (Crl:CD (SD) 

IGS BR) at doses of 100, 300 or 1000 mg/kg/day for seven days a week for two weeks. No mortality or 

clinical effects were observed. There was a low incidence of slight erythema and/or edema in rats 

exposed to DBE, DMA, DMG, or DMS. Minimal to mild erythema was observed in males and females 

treated with DBE, DMA and DMG. Generally minimal to mild dermal irritation in the form of focal 

eschar (scabbing) formation and desquamation was observed in rats treated with DBE, DMA, DMG, and 

DMS. All observed effects were reversible. (Kirkpatrick, 2000)

Systemic Effects NOAEL= 1000 mg/kg/day (highest dose tested)

Systemic Effects LOAEL not established

INHALATION

(DMS, DMG, DMA) 90-Day (rat) Inhalation (Bamberger, 2000)*-(Presented separately for ease of 

reading):

DMS

 *

Summary Taken directly from EPA’s 2008 “Supporting Documents for Initial Risk-Based Prioritization of High Production 

Volume Chemicals” for Dibasic Esters. 
16

Sprague-Dawley rats were exposed to DMS via inhalation at 0 or 400 mg/m3 (0.4 mg/L), 6 hours/day, 5 

days/week for 90 days. A 1-month recovery group was included in the study. Neurobehavioral test 

battery; evaluation of male reproductive organs including sperm count, motility and morphology; cell 

proliferation (CP—hepatic, lung, and nasal tissues); female estrous cycle determination; and hormonal 

analysis (serum leutenizing hormone (LH), follicle stimulating hormone (FSH) and testosterone in males 

and serum estradiol and progesterone concentrations in females) were included in the test. Testsubstance-related effects seen in the noses of male and female rats at 400 mg/m3 DMS included 

degeneration/atrophy and focal respiratory metaplasia of the olfactory mucosa with minimum to mild 

severity. Degeneration/atrophy of the olfactory mucosa was evident in recovery animals in the same 

locations as observed in the animals examined after 90 days of exposure. Male rats exposed to 400 

mg/m3 showed marked increase in CP in the liver and the females had greater CP in the nose level III 

relative to controls. Females showed a statistically significant decrease (43% of control) in serum 

estradiol concentrations; however, the change in estradiol was not observed in the other two studies 

therefore, it was not considered adverse. In male rats, epididymal sperm counts were significantly 

increased (141 – 153% of control) but other sperm parameters were not affected. Hence, the changes in 

epididymal sperm count were not considered as adverse.

NOAEL not established

LOAEL = 400 mg/m3 (0.4 mg/L); based on effects on nasal tissues, decrease in estradiol concentration 

in females and increased epididymal sperm counts in males

DMG

Sprague-Dawley rats were exposed to DMG via inhalation at 0, 10, 50 or 400 mg/m3 (0, 0.01, 0.05 or 

0.4 mg/L), 6 hours/day, 5 days/week for 90 days. A 1-month recovery group was included in the study. 

Neurobehavioral test battery; evaluation of male reproductive organs including sperm count, motility 

and morphology; cell proliferation (CP—hepatic, lung, and nasal tissues); female estrous cycle 

determination; and hormonal analysis (serum LH, FSH and testosterone in males and serum estradiol 

and progesterone concentrations in females) were included in the test. Male rats exposed to 400 mg/m3

showed lower mean body weight and body weight gains during the study and male and female rats had 

lower food consumption. Test substance-related effects seen in the noses of male and female rats at 400 

mg/m3 DMG included degeneration/atrophy and focal respiratory metaplasia of the olfactory mucosa 

with minimum to mild severity. Degeneration/atrophy of the olfactory mucosa was evident in recovery 

animals in the same locations as observed in the animals examined after 90 days of exposure. Male and 

female rats exposed to 400 mg/m3 DMG showed marked increase in CP in the nose level III. Male rats 

showed a statistically significant decrease in serum testosterone levels at 50 and 400 mg/m3 (59 and 50% 

of control, respectively). Serum LH concentration was decreased in a dose-dependent manner and was 

statistically significant at 400 mg/m3 (71% of control). In addition, a significant increase in epididymal 

sperm count was seen in the animals exposed to 50 and 400 mg/m3 (124 and 131% of control,

respectively); however, other sperm parameters were not affected.

NOAEL = 10 mg/m3 (0.01 mg/L)

LOAEL = 50 mg/m3 (0.05 mg/L), based on decrease in serum LH concentration in a dose-dependent 

manner, decrease in testosterone concentration, effects on nasal tissues, increased epididymal sperm 

counts at 50 mg/m3 and above in males

DMA

Sprague-Dawley rats were exposed to DMA via inhalation at 0 or 400 mg/m3 (measured as 390 mg/m3; 

0.39 mg/L), 6 hours/day, 5 days/week for 90 days. A 1-month recovery group was included in the study. 
17

Neurobehavioral test battery; evaluation of male reproductive organs including sperm count, motility,

and morphology; cell proliferation (CP—hepatic, lung, and nasal tissues); female estrous cycle 

determination; and hormonal analysis (serum LH, FSH and testosterone in males and serum estradiol 

and progesterone concentrations in females) were included in the test. Test-substance-related effects 

seen in the noses of male and female rats at 400 mg/m3 DMA included degeneration/atrophy and focal 

respiratory metaplasia of the olfactory mucosa with minimum to mild severity. Degeneration/atrophy of 

the olfactory mucosa was evident in recovery animals in the same locations as observed in the animals 

examined after 90 days of exposure. Male rats exposed to 400 mg/m3 showed marked increase in CP in 

the liver and had greater CP in the nose level II relative to controls. Female rats exposed to 400 mg/m3

had greater CP in the lungs relative to controls. In male rats, although not statistically significant, an 

increase in epididymal sperm counts was noted.

NOAEL not established

LOAEL = 400 mg/m3 (0.4 mg/L); based on effects on nasal tissues, increase in CP in liver, lungs and 

nose

(DBE) 90-Day (rat) Inhalation

In a 90-day inhalation toxicity study, CRL:CD®BR rats were exposed to DBE aerosol-vapor mixture at 

160, 400 or 1000 mg/m3 (~0.160, 0.400 or 1.0 mg/L) 6 hours/day, 5 days/week for approximately 14 

weeks. Microscopic examination of nasal tissues showed degeneration of the olfactory epithelium in all 

DBE-exposed groups. Effects were of minimal severity in the 160 mg/m3 group and mild to moderate at 

the mid- and high-concentrations. Dose-dependent decreases in absolute and relative liver weights were 

observed in female rats in all exposed groups and males exposed to 1000 mg/m3. However, a 

histopathologic examination revealed no toxic effects in the liver and therefore, the biological 

significance of the reduced liver weights is unknown. Other statistically significant differences between 

test and control rats in the 1000 mg/m3 group included slight increases in relative heart and testes 

weights in males and a slight decrease in absolute spleen weight in females. These slight organ weight 

changes were not accompanied by any histopathological changes and are therefore, considered not

adverse. There were also slight decreases in blood sodium concentrations in both male and female rats 

exposed to 1.0 mg/L DBE, and slight increases in blood calcium concentrations in female rats exposed 

to 0.40 mg/L and 1.0 mg/L of DBE. These slight changes in blood sodium and calcium levels were not

considered to be adverse since these changes were minor in magnitude and there was no clear dose 

response. (MRID 45740503)

NOAEL not established

LOAEL = 160 mg/m3 (0.16 mg/L); based on degeneration of olfactory epithelium

(DBE) 90-Day (rat) Inhalation

In another 90-day inhalation toxicity study (OSCPP 870.3465), Crl:CD/BR male and female rats were 

exposed to DBE at 20, 76 or 390 mg/m3 (0.02, 0.076 or 0.39 mg/L) for 13 weeks. The results indicated 

degeneration of olfactory epithelium in male rats exposed to 76 or 390 mg/m3 and in female rats 

exposed to all test concentrations. At the end of the 6-week recovery period, these effects were still 

visible in affected animals. Absolute liver weights in female rats exposed to 390 mg/m3 were decreased, 

but the liver-to-body weight ratios were not different from the controls. Liver weights were normal after 

the six week recovery period and there were no toxic effects observed histopathologically. A slight 

decrease in sodium levels was evident in all female exposure groups and males exposed to 76 and 390 

mg/m3. After 6 weeks of recovery, the sodium level was still low in animals exposed to 390 mg/m3. 
18

These changes were slight and generally within the range of biological variation and therefore, not 

considered to be toxicologically relevant. (MRID 48968819)

NOAEL not established 

LOAEL = 20 mg/m3 (0.02 mg/L); based on degeneration of olfactory epithelium 

3.2.4 Reproductive and Developmental Toxicity

(DBE) Reproductive and Developmental Toxicity (rat) Inhalation

In a combined study, thirty Sprague Dawley rats of each sex were exposed to dibasic esters for 6 hours a 

day, 5 days a week for 15 weeks to 0, 160, or 400 mg/m3 of DBE vapor or to 1000 mg/m3 of DBE 

aerosol-vapor mixture. Ten rats/sex/group were necropsied after 15 weeks. The remaining 20 

rats/sex/group were exposed in the reproduction study through breeding, gestation and lactation periods. 

Ten pups/sex/group were necropsied at age 21 days. In the teratology part of the study 24 pregnant rats 

per group were exposed to DBE on gestation days 7-16 and euthanized on day 21. Effects seen after 15 

weeks were slightly depressed body weights and depressed male liver weights at 1000 mg/m3 and doserelated depressed liver weights in all exposed females. There were no histological findings other than a 

dose-related mild degeneration of the olfactory epithelium in all DBE exposed groups. There were no 

reproductive effects except for depressed pup weights in the 1000 mg/m3 group, and no effects in the 

teratology study except for an increased incidence of delayed renal papillary development which was not 

considered to be compound related instead a result of an unusually low control group value relative to 

the relevant historical control values. (MRID 48968822)

Maternal NOAEL= 400 mg/m3

Maternal LOAEL= 1000 mg/m3 based on depressed body weight

Reproductive NOAEL= 400 mg/m3 

Reproductive LOAEL= 1000 mg/m3 based on depressed pup weight

Developmental NOAEL= 1000 mg/m3 (highest dose tested) 

Developmental LOAEL not established

(DMG) Developmental Toxicity (rabbit) Inhalation

A developmental inhalation study was carried out on Hra:(NZW)SPF rabbits exposed to Dimethyl 

glutarate (DMG) for approximately 6 hours each day on gestation days 7 through 28 at concentrations of 

30, 100, 300, or 1000 mg/m3

. Maternal body weight, food consumption, and clinical observation data 

were collected daily. Animals were euthanized on day 29 of gestation and subjected to a gross external 

and internal postmortem examination. Gravid uteri were removed, weighed, and dissected and the 

uterine contents were evaluated. Each live fetus was weighed, sexed, and examined for external, 

visceral, and skeletal alterations. 

There was no evidence of maternal toxicity at 30 or 100 mg/m3 and there was no evidence of 

developmental toxicity at any level tested. At 1000 mg/m3 one animal was found dead on gestation day 

13 and one animal was sacrificed in extremis on gestation day 22. Among survivors there were 

reductions in maternal body weight gains and food consumption and there were compound-related 

clinical observations (ocular discharge and wet fur). At 300 mg/m3, evidence of maternal toxicity was 

limited to reduced maternal body weight gains and increased clinical observations (ocular discharge). 

There was a significant decrease in sternal ossifications at 1000 mg/m3

; however, it was not considered 

to be compound related rather the result of an unusually low control group value relative to historical 

control group data. (Munley, 2003)
19

Maternal NOAEL= 100 mg/m3

Maternal LOAEL= 300 mg/m3 based on body weight gains and clinical observations

Developmental NOAEL= 1000 mg/m3 (highest dose tested)

Developmental LOAEL not established

(DBE) Developmental Toxicity (rat) Inhalation

A group of pregnant female Crl:CD®BR rats were exposed to either 0.16, 0.4, or 1.0 mg dibasic esters 

(DBE)/L (160, 400 or 1000 mg/m3

) by inhalation for 6 hr/day from Days 7 through 16 of gestation

(OSCPP 870.3700). A suppression of both food consumption and the rate of body weight gain was seen 

in the 0.4 and 1.0 mg/L groups during the first 6 exposure days. Staining on the fur and perineal area 

was seen in rats exposed to 1.0 mg/L and liver weight decreases, although not statistically significant, 

occurred in the 2 high exposure groups. All female rats were euthanized on gestation Day 21 and the 

fetuses were examined. None of the reproductive parameters were altered in any of the groups and no 

fetal effects were observed. DBE was not observed to be a developmental toxin in the rat following 

inhalation exposures as high as 1.0 mg DBE/L (1000 mg/m3). (MRID 48968820)

Maternal NOAEL = 160 mg/m3

Maternal LOAEL = 400 mg/m3 based on food consumption and body weight gain

Developmental NOAEL = 1000 mg/m3 (highest dose tested)

Developmental LOAEL not established

REPRODUCTIVE AND DEVELOPMENTAL TOXICITY Studies on Metabolites –

See Table 6

(Glutaric acid) Developmental Toxicity (rat) Oral

Groups of pregnant female CD rats were administered doses of glutaric acid at 0, 125, 400 and 1300 

mg/kg/day via gavage on gestation days 6 – 15. Animals were sacrificed on gestation day 20 and 

examined for any gross pathological changes. At 400 mg/kg/day and higher, clinical signs such as 

salivation, rales, and nasal discharge were observed. Mean body weight gain was decreased at 1300 

mg/kg/day during the dosing period, but they were comparable to control animals during post-dosing 

(GD 15 – 20). Animals dosed with 1,300 mg/kg also exhibited slight inactivity, labored breathing, 

decreased body temperature, soft stool, and staining around the mouth, nares, and anogenital area. At

1300 mg/kg/day, one female died and one was sacrificed on gestation day 13. No changes were seen in 

reproductive status. There were no effects on the number of corpora lutea, implantation sites, number of 

live and dead fetuses or fetal body weights. No differences were seen in visceral and skeletal 

abnormalities between the control and the treatment groups. No adverse effects on pregnancy and no 

teratogenic effects were observed. A marked increase in the number of resorptions was observed at 1300 

mg/kg/day. The number or resorptions was within normal expected limits; therefore, the increase was 

not considered biologically meaningful. (EPA, 2008c)

Maternal NOAEL = 125 mg/kg/day

Maternal LOAEL = 400 mg/kg/day based on salivation, rales, and nasal discharge

Developmental NOAEL = 1300 mg/kg/day

Developmental LOAEL not established

(Glutaric acid) Developmental Toxicity (rabbit) Oral

Groups of pregnant female New Zealand White rabbits were administered glutaric acid at 0, 50, 160 and 

500 mg/kg/day via gavage on days 6 – 18 of gestation; females were sacrificed on gestation day 29 and 
20

examined for gross pathological changes. No changes were seen in reproductive status. There were no 

effects on the number of corpora lutea, implantations, number of live and dead fetuses, resorptions, fetal 

body weights or external, visceral and skeletal abnormalities. There were no adverse effects on 

pregnancy and no embryotoxic or teratogenic effects were observed. (EPA, 2008c)

Maternal NOAEL = 500 mg/kg/day (highest dose tested)

Maternal LOAEL not established

Developmental NOAEL = 500 mg/kg/day (highest dose tested)

Developmental LOAEL not established

(Adipic acid) Developmental Toxicity (rat) Oral

Groups of pregnant female Wistar rats were administered adipic acid via gavage at 0, 2.9, 13, 62 and 

288 mg/kg/day during gestation days 6 – 15. Females were sacrificed on gestation day 20 and were 

examined for any gross pathological changes. There were no effects on the number of corpora lutea, 

implantations, number of live and dead fetuses, resorptions, fetal body weights, or external, visceral and 

skeletal abnormalities. (EPA, 2008c)

Maternal NOAEL = 288 mg/kg/day (highest dose tested)

Maternal LOAEL not established

Developmental NOAEL = 288 mg/kg/day (highest dose tested)

Developmental LOAEL not established

(Adipic acid) Developmental Toxicity (rat) Oral

Groups of pregnant female Dutch-belted rabbits were administered adipic acid at 0, 2.5, 12, 54 and 250 

mg/kg/day via gavage on gestation days 6-18; females were sacrificed on gestation day 29 and examined 

for gross pathological changes. No changes were seen in reproductive status. There were no effects on 

the number of corpora lutea, implantations, number of live and dead fetuses, resorptions, fetal body 

weights, and external, visceral and skeletal abnormalities. There were no adverse effects on pregnancy 

and no embryotoxic or teratogenic effects were observed. (EPA, 2008c)

Maternal NOAEL = 250 mg/kg/day (highest dose tested)

Maternal LOAEL not established

Developmental NOAEL = 250 mg/kg/day (highest dose tested)

Developmental LOAEL not established

(Adipic acid) Developmental Toxicity (mouse) Oral

Groups of pregnant female CD-1 mice were administered adipic acid via gavage at 0, 2.6, 12, 56 and 

263 mg/kg/day during gestation days 6 – 15. There were no effects on the number of implantations, 

number of live and dead fetuses, resorptions, fetal body weights, or external, visceral and skeletal 

abnormalities. (OECD, 2006)

Maternal NOAEL = 263 mg/kg/day (highest dose tested)

Maternal LOAEL not established

Developmental NOAEL = 263 mg/kg/day (highest dose tested)

Developmental LOAEL not established
21

Table 6. Summary of Toxicological Endpoints for Metabolites of DMEGSA: Glutaric 

Acid, Adipic Acid, and Succinic Acid

Study Test Substance Toxicological Effect Reference

13-Week Oral

(Rat)

Succinic Acid (as 

Monosodium 

Succinate)

NOAEL= ~1,250 mg/kg/day

LOAEL= ~2,500 mg/kg/day; decreased body 

weight gain

EPA, 2008c

90-Day Oral

(Rat) Glutaric Acid

NOAEL= ~500 mg/kg/day 

LOAEL= ~1,000 mg/kg/day; decreased body 

weight gain

EPA, 2008c

90-Day Oral 

(Dog) Glutaric Acid

NOAEL= ~500 mg/kg/day 

LOAEL= ~750 mg/kg/day; decreased body 

weight gain

EPA, 2008c

2 Year Oral

(Rat) Adipic Acid

NOAEL= ~750 mg/kg/day 

LOAEL= ~2,250; decreased body weight gain 

and food consumption

Horn, 1957

Developmental 

Oral 

(Rat)

Glutaric Acid

Maternal NOAEL= 125 mg/kg/day

Maternal LOAEL= 400 mg/kg/day; salivation, 

rales, and nasal discharge

Developmental NOAEL= 1,300 mg/kg/day 

(HDT)

Developmental LOAEL not established

EPA, 2008c

Developmental 

Oral 

(Rabbit)

Glutaric Acid

Maternal NOAEL= 500 mg/kg/day (HDT)

Maternal LOAEL not established

Developmental NOAEL= 500 mg/kg/day (HDT)

Developmental LOAEL not established

EPA, 2008c

Developmental 

Oral

(Rat)

Adipic Acid

Maternal NOAEL= 288 mg/kg/day (HDT)

Maternal LOAEL not established

Developmental NOAEL= 288 mg/kg/day (HDT)

Developmental LOAEL not established

EPA, 2008c

Developmental 

Oral

(Rat)

Adipic Acid

Maternal NOAEL= 250 mg/kg/day (HDT)

Maternal LOAEL not established

Developmental NOAEL= 250 mg/kg/day (HDT)

Developmental LOAEL not established

EPA, 2008c

Developmental 

Oral

(Mouse)

Adipic Acid

Maternal NOAEL= 263 mg/kg/day (HDT)

Maternal LOAEL not established

Developmental NOAEL= 263 mg/kg/day (HDT)

Developmental LOAEL not established

OECD, 2006

3.2.5 Neurotoxicity

In the previously reviewed 90-day inhalation studies (Bamberger, 2000) described above, DMA, DMG, 

and DMS did not induce neurotoxicity in rats at doses up to 0.4 mg/L. There were no microscopic 

neuropathological changes that could be attributed to exposure to these chemicals. In addition, no test 

substance-related effects on functional observational battery parameters in male and female rats exposed 

to DMA, DMG, or DMS were observed.

The agency concluded that based on the lack of neurotoxicity seen in any of the reviewed studies on the 

chemicals or their metabolites and the common use of the chemicals in food products it is unlikely that 

these chemicals would be neurotoxic.
22

3.2.6 Mutagenicity 

The following paragraph is a taken from the previous 2008 EPA’s “Decision Document for Petition 

#5E4442: Dibasic Esters”. References have been added for clarification

...submitted studies indicating that DBE was non-mutagenic in most assays 

(Salmonella/microsome (MRID 45740505), Salmonella/suspension and microforward (MRID 

45740509), and mouse bone marrow micronucleus assays (MRID 45740507), but caused 

chromosomal aberrations at concentrations greater than 0.3% in the chromosome aberration test. 

The Agency agrees that DBE is negative for mutagenicity in most tests, but positive for dosedependent increases in chromosomal aberrations in lymphocites. (MRID 45740508) 

The Agency reviewed additional mutagenicity studies sponsored by SOCMA when originally assessing 

the mutagenic potential for DBEs. DMA and DMG did not induce chromosome damage or bone marrow 

toxicity in male rats treated for two six-hour periods of whole body inhalation exposure to DMA or 

DMG at dose levels of 0.50, 1.0, or 2.0 mg/L (500 mg/m3

, 1000 mg/m3, or 2000 mg/m3). (Mason, 2001) 

DMG did not demonstrate mutagenic potential in an in vitro hypoxanthine-guanine phosphoribosyl 

transferase (HPRT) cell mutation assay, either in the presence or absence of S9 metabolic activation.

(Clare, 2002) Although DBE tested positive for dose dependent increases in chromosomal aberration in 

lymphocytes, it was negative in the in vivo micronucleus for chromosomal aberrations. 

Table 7. Summary of Genotoxicological Endpoints for DMEGSA Inert Ingredients for Use 

in Human Health Risk Assessments

Study Test Substance Toxicological Effect Reference

Mutagenicity: Microsome Assay

(Salmonella) DBE Negative MRID 45740505

Chromosome Abberation DBE S9(-): Negative

S9(+): Positive

MRID 45740508

Genotoxicity Mouse Micronucleus DBE Negative MRID 45740507

Rat micronucleus -

inhalation

DMG Negative Mason, 2001

3.2.7 Carcinogenic Potential 

No carcinogenicity studies are available on DMEGSA or DBE chemicals. In the absence of quantitative 

data a qualitative structure activity relationship (SAR) database, DEREK Version 11, was used to 

determine if there were structural alerts suggestive of carcinogenicity. No structural alerts were 

identified for DMG and DMS. In addition, the metabolites succinic acid and adipic acid have been 

evaluated for carcinogenicity in chronic studies and there was no increase in the incidence of tumors 

over that in the corresponding control group. (MRID 48968818; OECD, 2006)

3.3 Endpoint Selection and Levels of Concern

Repeated exposures to DMEGSA via inhalation show local effects (likely a result of irritation at the 

point of contact in the nasal region) as well as some changes in hormone levels that, although 

consistently observed, are not considered to be toxicologically significant. Although these studies 

showed changes in the cells of the nasal region (degeneration/atrophy with minimum to mild severity) in 
23

animals exposed daily for 90 days via the inhalation route of exposure, these effects on the olfactory 

epithelium are expected to be of much lower impact in humans due to major anatomical and 

physiological differences between rats and humans. Rats have a larger surface of nasal epithelium and 

different air flow and breathing pattern compared to humans (MRID 48968834; 48968835). The airflow 

is not directed to the olfactory epithelium to the same extent in the human nasal cavity so the local 

exposure will therefore be significantly lower in humans. In addition, rodents are obligate nasal 

breathers while humans breathe through both the mouth and nose. Rats also have greater 

carboxylesterase activity in nasal/olfactory epithelium than do humans (MRID 48968828; 48968832). 

“Preliminary in vitro experiments with human nasal tissue homogenates suggest that DBE metabolism 

in human nasal tissue is 100 to 1000 times less active that rat nasal tissue.” (US CPSC, 1994) Therefore,

humans are expected to be much less sensitive.

Exposed animals also showed microscopic alterations in the liver (males) and lung (females).The 

hormonal changes observed in these studies with DMS, DMA, and DMG were: an increase in sperm 

counts (2/3 studies), a decrease in testosterone levels (1/3 studies), and a decrease in leutenizing 

hormone levels (1/3 studies) in males and a decrease in estradiol levels in females (1/3 studies). The 

significance of these findings is unclear because the decrease in male hormone levels should result in a 

decrease in sperm counts, yet the opposite effect was observed. The single study showing changes in 

estradiol was not observed in the other two studies. Furthermore, there were no functional parameters 

such as estrous cycle and sperm motility or morphology affected. In addition, a reproductive study was 

conducted with DBE and there were no effects on fertility, viability of pups at birth, and the ability of 

the mothers to lactate. For these reasons the point of departure for the risk assessment for chronic oral 

routes of exposure was from the 14-day oral toxicity study in rats. The NOAEL was 842 mg/kg/day

and the LOAEL was 1684 mg/kg/day based on reduced weight gain and food consumption. A 1000

fold uncertainty factor was used for the chronic exposure (10X interspecies extrapolation, 10X for 

intraspecies variability and 10X FQPA factor (See Section 3.4 for more information on the FQPA safety 

factor)). 

The dermal study did not result in an endpoint of concern. Therefore, quantification of dermal risk is not 

necessary. Adverse local olfactory effects were observed in inhalation toxicity studies; however, due to 

anatomical and physiological difference between study animals and humans, the effects are likely to be 

less severe in humans and subsequently of minimal toxicological concern. No systemic endpoint of 

concern was identified in the available inhalation toxicity studies; therefore, quantification of inhalation 

risk is not necessary. The study and endpoint of concern used for estimation of chronic RfD was used 

for short-term and intermediate-term incidental oral estimation. The residential and aggregate level of 

concern (LOC) is for margins of exposure (MOE) that are less than 1000 and is based on 10X 

interspecies extrapolation, 10X for intraspecies variability and a 10X FQPA safety factor. No in vivo

dermal absorption studies are available for DBEs: however, the dermal absorption estimation was not 

necessary to quantify dermal exposure base on lack of a dermal endpoint of concern. 

3.4 FQPA Safety Factor Considerations

FFDCA section 408 provides that EPA shall apply an additional tenfold margin of exposure (safety) for 

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

completeness of the data base unless EPA determines that a different margin of exposure (safety) will be 

safe for infants and children. EPA concludes that the FQPA safety factor of 10X for DMEGSA should 
24

be retained because of the need to extrapolate from a subchronic study for a chronic risk assessment. 

Although the 10X FQPA safety factor has been retained due to the lack of a chronic oral study the 

following conditions have been met:

i. The toxicity database for DMEGSA and their metabolites includes several subchronic 

and chronic studies, several developmental and reproductive toxicity studies, and mutagenicity 

studies. No chronic studies are available on DBEs; however, chronic toxicity studies on 

metabolites are available to characterize long term toxicity potential of DBEs. 

ii. Increased incidence of delayed renal papillary development and decreased pup weights 

were observed in reproductive/developmental inhalation toxicity studies at 1000 mg/m3; 

however, these effects were only observed in the presence of depressed maternal body weight. 

In addition, there were no systemic effects seen in oral studies at doses up to and including the 

limit dose of 1000 mg/kg/day indicating no evidence of increased susceptibility. 

iii. There is no indication that DMEGSA are neurotoxic chemicals. Although no 

neurotoxicity studies are available in the database, no clinical signs of neurotoxicity were 

observed in the available subchronic and chronic studies. Therefore, there is no need for a 

developmental neurotoxicity study or additional UFs to account for neurotoxicity. 

vi. The dietary food exposure assessment utilizes proposed tolerance level or higher residues 

and 100% CT information for all commodities. By using these screening-level assessments, 

chronic exposures/risks will not be underestimated.

In conclusion, based on the absence of developmental toxicity for DBE in inhalation studies at 

maternally toxic doses and the higher developmental NOAEL for DMG there is no concern, at this time, 

for increased sensitivity to infants and children to DBE when used as an inert ingredient in pesticide 

formulations. However, due to the lack of a chronic oral toxicity study the 10X FQPA safety factor has 

been retained to protect infants and children. 

4.0 EXPOSURE ASSESSMENT

4.1 Dietary Exposure:

4.1.1 Acute exposure

No adverse effect attributable to a single exposure of DMEGSA was seen in the database. Therefore, an 

acute dietary risk assessment for DMEGSA is not required.

4.1.2 Chronic exposure

In conducting the chronic 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 DMEGSA. In the absence of specific residue data, EPA has 
25

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

the subject inert ingredient. 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 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.
26

Table 8. Summary of Chronic Dietary Exposure and Risk for APG

Population Subgroup cPAD 

(mg/kg/day)

Chronic

Exposure (mg/kg/day) % cPAD

General U.S. Population

0.842

0.189 22.6

All Infants (<1 year old) 0.394 46.8

Children 1-2 years old 0.706 83.9

Children 3-5 years old 0.486 57.7

Children 6-12 years old 0.251 29.8

Youth 13-19 years old 0.135 16.0

Adults 20-49 years old 0.145 17.2

Adults 50+ years old 0.152 18.0

Females 13-49 years old 0.146 17.4

Based on analyses of estimated dietary risks for the general U.S. population and various population 

subgroups, the chronic dietary exposure estimates for DMEGSA are below the agency’s level of concern 

for all supported commodities. The chronic dietary exposure estimate for the highest exposed population 

subgroup, children 1-2 years old, is 83.9% of the chronic population adjusted dose (cPAD).

4.1.3 Cancer 

Although there are no animal carcinogenicity studies available in the database, DMEGSA tested 

negative in mutagenicity and clastogenicity assays and no evidence of specific target organ toxicity was 

observed in any of the repeat dose studies. A qualitative structure activity relationship database, DEREK 

Version 11, was used to determine if there were structural alerts suggestive of carcinogenicity. No 

structural alerts were identified for DMG and DMS. Additionally, no evidence of carcinogenicity was 

observed in a two year feeding study on the metabolite adipic acid and monosodium succinate. The 

Agency does not anticipate DMEGSA to be carcinogenic; therefore, a carcinogenicity assessment was 

not performed. 

4.2 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). DMEGSA may be used as inert ingredients in 

pesticide products that are registered for uses that may result in residential exposures. The major routes

of exposure from residential uses are expected to be inhalation and dermal exposure; however, there is 

also a potential for incidental oral exposure in children exposed to areas that have been treated with 

pesticides containing the inert ingredient. Since no endpoint of concern was identified in the dermal 

study and the result seen in the inhalation studies were not expected to be significant in humans, only 

incidental oral exposure scenarios in children were conducted. Subsequently, residential handler 

scenarios were not assessed. A screening level residential exposure assessment was conducted to 

represent worst-case residential exposure and high end-use product application methods. The assessment 

methodologies were taken from: Standard Operating Procedures for Residential Pesticide Exposure 

Assessment. EPA/OPP/Health Effects Division February 2012. 
27

Table 9. Residential Post-application Short- and Intermediate-term Exposures and Risks for DMEGSA Inert

Ingredients

Exposure Scenario Application Rate1 Exposed Population & 

Exposure Duration2

Daily Dose 

(mg/kg/day)

MOE

Outdoor Products

Hand-to-Mouth from 

Treated Lawn

1.8 lb/day

Child ST 0.034 25000

Child IT 0.016 53000

Object-to-Mouth from 

Treated Lawn

Child ST 0.008 100000 Child IT

Soil Ingestion Child ST 0.0001 7500000 Child IT 1 Application rates are based on high end rates for similar products. 2 ST and IT indicate short- or intermediate-term exposure durations

EPA has calculated the residential post-application exposures for children exposed via hand-to-mouth or 

by placing nonfood objects that have come into contact with pesticides containing the inert ingredient in 

their mouth. Currently, there are no current or proposed residential pesticide uses for this inert 

ingredient; however, the agency evaluated this high level screening model in the event that future uses 

of this inert ingredient result in nonfood residential oral exposures to children. Of the three scenarios 

evaluated, the highest daily dose from exposure to treated lawns is from short-term and intermediateterm hand-to-mouth exposure scenarios at 0.034 and 0.016 mg/kg/day, respectively. The short-term 

MOE was calculated to be 25,000 and the intermediate-term MOE was 53,000. As the level of concern 

is for MOEs that are lower than 1000, these MOEs are not of concern.

4.3 Occupational Exposure

As stated in Section 3.3 of the document, repeated exposures to DMEGSA via inhalation show local 

effects (likely a result of irritation at the point of contact in the nasal region) as well as some changes in 

hormone levels that, although consistently observed, are not considered to be toxicologically significant.

Expected exposure from occupational use of DMEGSA is via the dermal and inhalation routes of 

exposure. Because no endpoints of concern have been identified in dermal or inhalation studies a 

qualitative occupational assessment was conducted. 

5.0 Aggregate Risk and Determination of Safety 

Acute and chronic pesticide exposures are evaluated by the agency by comparing aggregate exposure 

estimates to the acute and chronic population adjusted dose (aPAD, 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 to ensure that the MOE called for by the product of all applicable 

UFs is not exceeded. 

5.1 Acute Dietary Risk. 

No hazard attributable to a single exposure seen in the toxicity database for the DMEGSA; therefore an 

acute aggregate risk assessment was not conducted. 
28

5.2 Chronic Dietary Risk.

A chronic dietary risk assessment takes into account exposure estimates from chronic dietary consumption of food and drinking water using the exposure assumptions discussed in section 4.1.2 for chronic 

exposure. The chronic analysis was based on a toxicity study in rats with a NOAEL of 842 mg/kg/day 

and LOAEL of 1684 mg/kg/day based on body weight gain and food consumption. A 1000-fold 

uncertainty factor (UF) (10X for interspecies extrapolation, 10X for intraspecies variation, and 10X 

FQPA safety factor) was incorporated. The chronic dietary exposure from food and water to DMEGSA 

is 22.6% of the cPAD for the U.S. population and 83.9% of the cPAD for children 1-2 yrs old, the most 

highly exposed population subgroup. 

5.3 Cancer Risk for U.S. Population. 

The Agency has not identified any concerns for carcinogenicity relating to DMEGSA; therefore, a 

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

concern.

5.4 Short-Term/Intermediate Aggregate Risk. 

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

exposure to food and water (considered to be a background exposure level). DMEGSA could be used as 

an inert ingredient in pesticide products that could result in short-term and intermediate-term residential 

exposure. Using the exposure assumptions described in section 4.1.2, EPA has calculated the combined 

short- and intermediate term aggregated food, water, and residential oral exposures. EPA has concluded 

the combined short-term and intermediate aggregated food, water, and residential oral exposures for 

children resulted in an aggregate MOEs of 1450 and 1500, respectively. As the level of concern is for 

MOEs that are lower than 1000, these MOEs are not of concern.

Table 10. Short-Term and Intermediate-Term Aggregate Risk for DMEGSA

Population

LOC for 

Aggregate

Risk1

mg/kg/day; (MOE)

food & water2

mg/kg/day; (MOE)

residential3

Aggregate MOE

(food and 

residential)4

Short-Term

Child 1000 0.547; (1500) 0.034; (25000) 1450

Intermediate-Term

Child 1000 0.547; (1500) 0.008; (100000) 1500 1 The LOC is based on a 1000X safety factor for inter- and intra-species extrapolation and 10 FQPA SF 2 MOE food = [(short- or intermediate-term oral NOAEL)/(chronic dietary exposure)]. Chronic dietary exposure values from Table 8 3 MOE residential from Table 9 4 Aggregate MOE (food and residential) = NOAEL/(mg/kg/day (food and water) +mg/kg/day (residential))

6.0 Cumulative Risk

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 
29

particular pesticide's residues and “other substances that have a common mechanism of toxicity.” EPA 

has not found DMEGSA to share a common mechanism of toxicity with any other substances, and 

DMEGSAs do not appear to produce a toxic metabolite produced by other substances. For the purposes 

of this tolerance action, therefore, EPA has assumed that the DMEGSA 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.

7.0 Environmental Fate 

In determining the environmental fate of DMEGSA the Agency considered data submitted by the 

petitioner as well as information available from the Hazardous Substances Data Bank (HSDB), the 

EPA’s HPV Document for Dibasic Esters, the Decision Document for Petition #5E4442 and the robust 

summaries of DBE, DMA, DMG, and DMS sponsored by SOCMA (2002) as part of the EPA HPV 

Challenge Program. See Tables 1-3 for the physical/chemical properties for these chemicals. 

DMA, DMG, and DMS have similar physical-chemical properties and are components of the mixture 

DBE. As with its component chemicals, DBE is expected to photodegrade when released to air, with a 

half-life of ranging from 3-24 days. If released to soil, DBE is expected to have high mobility through 

soil, based on its Log Kow. In a microbial biodegradation test using the shake-flask method, DBE had a

half-life of 2.5 to 3.2 days. DMG degraded 98% after 28 days and DMS degraded >95% after 10 days in 

aerobic tests with activated sludge. 

If released to water, DBE is not expected to volatilize from surface waters or adsorb to suspended solids 

and sediments in water column, but will biodegrade in the presence of bacteria in a matter of days and 

hydrolyze in a matter of months to years depending on pH. Based on the moderate vapor pressure it is 

believed that these chemicals will be moderately volatile and that when released to the atmosphere they 

will exist primarily in the vapor phase.

The estimated Log BCF indicates that the potential for bioaccumulation is low. They are not persistent 

(B1) and are not bioaccumulative (P1). 

8.0 Ecological Effects

8.1 Acute Fish Toxicity

Brachydanio rerio

Brachydanio rerio were exposed to DMS. Limited study information was available. The 96-hour LC50

= 50-100 mg/L. (EPA, 2008b)

Lepomis macrochirus

Bluegill sunfish (Lepomis macrochirus); 10/per concentration were exposed to DMG at nominal 

concentrations of 20-50 mg/L for 96 hours under static conditions. The 96-hour LC50 = 30.9 mg/L.

(EPA, 2008b)

Pimephales promelas
30

Fathead minnows (Pimephales promelas) were exposed to DBE with the test medium in a non-GLP

test with a protocol comparable to EPA’s test guideline OPPTS 850.1075 (Fish Acute Toxicity Test).

The test animals were exposed to nominal concentrations of 0, 10, 13, 18, 24, 32, 42, 56, 75, and 100 

ppm (v/v) under static conditions.

The temperature, pH, and oxygen in the medium were maintained. DBE exhibited moderate acute

toxicity to fathead minnows under static, unaerated test conditions during a 96-hour exposure. The 96-

hour LC50 ranged between the No Observed Effect Concentration (NOEC) of 18 ppm (v/v) and the

Lowest Observed Effect Concentration (LOEC) of 24 ppm (v/v). Therefore, the 96-hour LC50 of DBE 

to fish was estimated to be greater than 18 ppm (v/v) but less than 24 ppm (v/v) in laboratory

supply water. (EPA, 2008b)

8,2 Acute Invertebrate Toxicity

Daphnia magna

D. magna (20/concentration) were exposed to DMA at mean measured concentrations of 6.9, 14, 29, 58 

or 120 mg/L for 48 hours under static conditions. The 48-hour EC50 = 72 mg/L. (EPA, 2008b)

Daphnia magna

Two studies on DBE exposed D. magna at concentrations of 100 to 300 mg/L and 112 and 150 mg/L for 

48 hours under static conditions. The 48-hour EC50 were 136 mg/L and >112 and < 150 mg/L, 

respectively. (EPA, 2008b) 

Daphnia magna

In another study (OSCPP 850.1010), DME was tested for acute toxicity to Daphnia magna. Twenty

daphnids were exposed to DME for 24 hours at concentrations of 39, 90, 120, 140, 200, 290, 440, and 

680 mg/L. No immobilization was observed up to 120 mg/L and 100% mortality was observed at 290 

mg/L. The NOEC was 120 mg/L and the LOEC was 140 mg/L. Therefore, the 24-hour EC50 for DME 

was calculated to be 180 mg/L by graphical means. (MRID 48968812)

8.3 Acute Algal Toxicity

Pseudokirchneriella subcapitata

Green algae (Pseudokirchneriella subcapitata) were exposed to DMA for 72 hours at measured

concentrations of 6.25, 12.5, 25, 50, and 100 mg/L, under static conditions. The EC50 (biomass) >100 

mg/L and EC50 (growth) >100 mg/L. (EPA, 2008b)

Pseudokirchneriella subcapitata

A 72-hour Algal Growth Inhibition Test (OSCPP 850.4500) for DME was performed on 

Pseudokirchneriella subcapitata. The measured concentrations of the test item in the test media of the 

test concentrations of 4.6, 10, 22, 46, and 100 mg/L were 99 and 100% of the nominal values, 

respectively, at the start of the test. At the end of the test, 62 to 72% of the nominal values were found. 

The mean measured test concentrations were between 78 and 85% of the nominal values. 
31

DME had a statistically significant inhibitory effect on the growth of the algae (average growth rate

and yield) after the test period of 72 hours at the mean measured concentration of 85 mg/L. Thus, this 

concentration was determined to be the 72-hour LOEC. The 72-hour NOEC was determined to be

36 mg/L, since up to and including this mean measured test concentration, the growth rate and yield 

of the algae after 72 hours were not statistically significantly lower than in the control (MRID 

48968824).

9.0 Risk Characterization 

DBE has been previously approved by the agency under 40 CFR 180.1277 for use as a solvent and/or 

anti-freeze at 10% w/w or less in microencapsulated pesticide formulations with the active ingredient 

cyfluthrin. In addition, DMEGSA are used as solvents, plasticizers, polymer intermediates, and as 

components in paint strippers, polishes, and lacquer thinners. DMS and the metabolites adipic acid and 

succinic acid are considered GRAS chemicals and are directly added to food. Methanol, a metabolite of 

DMEGSA, is an approved food use inert ingredient in pesticide formulations under 40 CFR Part 

180.910 and 180.920 as a solvent and 180.930 as a solvent/co-solvent.

Various inhalation and in vitro studies have shown that DMEGSA is hydrolyzed to its corresponding 

monomethyl esters and subsequent dicarboxylic acid metabolites (i.e., adipic, glutaric, and succinic 

acid) by carboxylesterases located in the nasal/olfactory epithelium. Carboxylesterases are also found in 

many other mammalian tissues including the liver, kidney, brain, testis, and gastrointestinal tract. 

Following oral exposure, dimethyl esters are expected to be metabolized in the body similar to what 

was seen in rodent nasal mucosa; however, different areas of the body may be more or less efficient at 

metabolizing DBEs. For instance, olfactory mucosal homogenates hydrolyze DBE to their 

corresponding metabolites more efficiently (7 to 10 fold higher) than respiratory mucosal homogenates.

Acute toxicity studies conducted with DME demonstrate low acute oral and dermal toxicity. DME 

showed minimal eye irritation and no dermal irritation. A dermal penetration study conducted with DBE 

demonstrated that the dermal absorption rate is higher in rat skin compared to human skin (2.12 x 10-3 to 

4.18 x 10-3 cm/h versus 6.81 x 10-5 to 1.69 x 10-4

cm/h, respectively). Results of a dermal sensitization 

conducted with DME were negative.

The repeat dose database for DMEGSA contains oral, dermal, and inhalation studies. Due to their 

prevalence in commercial paint strippers, polishes, and lacquer thinners the majority of the studies were 

conducted via inhalation, the most expected route of exposure from non-pesticidal uses. The relevance 

of these studies to humans is discussed later in this section. 

Two oral rat studies have been conducted on DBE, a 14-day and a one month study. Animals in the 14-

day study showed reduced weight gain and food consumption at 1,684 mg/kg/day but showed no 

adverse effects at 842 mg/kg/day. Animals in the one month study showed no adverse effects at the 

limit dose of 1,000 mg/kg/day. A 14-day dermal study was also conducted with DBE and DMEGSA. 

Although mild skin irritation was noted in rats at doses equal to and greater than 100 mg/kg/day, the 

effects were reversible and no systemic effects were observed at any dose tested up to the limit dose of 

1,000 mg/kg/day. 
32

Based on the limited oral data for DMEGSA oral studies on the metabolites were also used to support a 

safety finding for DMEGSA. Available repeat dose oral studies on the metabolites include a 13-week 

study on succinic acid, two 90-day studies on glutaric acid and a two year study on adipic acid. Succinic 

acid was shown to cause decreased body weight gain in rats at and above 2,500 mg/kg/day. Glutaric 

acid also caused a decrease in body weight gain in both rats and dogs at 1,000 and 750 mg/kg/day, 

respectively. Similarly, adipic acid was seen to cause decreased body weight gain and food 

consumption in rats at 2,250 mg/kg/day. The results of these studies indicate that the metabolites of 

DMEGSA are of low toxicity via the oral route of exposure. 

The majority of the repeat dose and reproductive/developmental studies conducted on DBE and/or 

DMEGSA are via the inhalation route of exposure. The available database includes three 90-day 

inhalation studies in rats, one conducted with DMEGSA and two with DBE. In the first study rats were 

exposed to DMS and DMA at doses of 0 or 0.4 mg/L and DMG at doses of 0, 0.01, 0.05, or 0.4 mg/L. 

Degeneration of the olfactory epithelium was observed for all chemicals at and above 0.05 mg/L with 

the severity of the effect being dose dependent. Exposed animals also showed microscopic alterations in 

the liver (males) and lung (females).The hormonal changes observed in these studies with DMS, DMA, 

and DMG were: an increase in sperm counts (2/3 studies), a decrease in testosterone levels (1/3 studies), 

and a decrease in leutenizing hormone levels (1/3 studies) in males and a decrease in estradiol levels in 

females (1/3 studies). The significance of these findings is unclear because the decrease in male 

hormone levels should result in a decrease in sperm counts, yet the opposite effect was observed. The 

single study showing changes in estradiol was not observed in the other two studies. Furthermore, there 

were no functional parameters such as estrous cycle and sperm motility or morphology affected. In 

addition, a reproductive study was conducted with DBE and there were no effects on fertility, viability 

of pups at birth, and the ability of the mothers to lactate.

The two other 90-day rat studies tested DBE and again, degeneration of the olfactory epithelium was 

noted at all doses tested (0.02-1.0 mg/L). In both studies decreases in liver weight were observed but no 

histopathological findings were evident. Similarly, when rats were exposed to 1 mg/L DBE slight 

increases in relative heart and testes weights in males and a slight decrease in absolute spleen weight in 

females were observed. These slight organ weight changes were not accompanied by any 

histopathological changes and are therefore considered of minimal biological significance. No other 

significant effects were observed. 

Repeat dose inhalation studies have demonstrated the chemicals potential to affect the olfactory mucosa 

in the nasal passage of rats. These local effects are believed to be related to the hydrolysis of DMEGSA 

by carboxylesterases located in the nasal/olfactory epithelium to the dicarboxylic acid metabolites. 

These effects on the olfactory epithelium are expected to be of much lower impact in humans due to 

major physiological differences between rats and humans. Rats have a larger surface of nasal epithelium 

and different air flow and breathing pattern compared to humans. The airflow is not directed to the 

olfactory epithelium to the same extent in the human nasal cavity so the local exposure will therefore be

significantly lower in humans. In addition, rodents are obligate nasal breathers while man breathes 

through both the mouth and nose. Rats also have greater carboxylesterase activity in nasal/olfactory

epithelium than do humans. “Preliminary in vitro experiments with human nasal tissue homogenates 

suggest that DBE metabolism in human nasal tissue is 100 to 1000 times less active that rat nasal 

tissue.” (US CPSC, 1994) Therefore, humans are expected to be less much sensitive.
33

In addition to much of the repeat dose testing, inhalation was also the route of exposure used in much of 

the reproductive and developmental studies. Depressed pup weights were observed in a one-generation 

reproduction inhalation toxicity study with DBE at 1.0 mg/L but were only seen in the presence of 

maternal toxicity. Two developmental inhalation toxicity studies were conducted, one testing DBE on 

rats and with DMG on rabbits. In both studies no developmental effects were observed at doses up to 

and including 1.0 mg/L. Similarly, no adverse developmental effects were observed in oral studies on 

the metabolites glutaric acid (rat and rabbit) and adipic acid (rat and mice) at doses up to and including 

1,300 mg/kg/day.

An Ames test conducted with DBE was negative; however, a chromosome aberration study conducted 

with DBE was positive at high concentrations (3.3 and 4.4 mg/mL) in the presence of S9 metabolic

activation (negative without S9 activation) in lymphocytes from female donors. This result is not 

consistent with what is known about the hydrolysis products of the methyl esters. Methanol is not 

clastogenic or genotoxic. Glutaric acid, succinic acid, and adipic acid are all endogenous and not 

considered to be clastogenic or genotoxic; a chromosome aberration study conducted with adipic acid 

was negative. As such, it is possible that, in the presence of S9 metabolic activation, the esters were 

hydrolyzed and the acids released, affecting the pH, making it more acidic. This is known to cause

false positive effects in cytogenicity assays. Therefore, an in vivo genotoxicity assay on somatic cells 

was performed. A bone marrow micronucleus assay was performed in mice following a single

inhalatory nose-only exposure to DBE for six hours. There were no statistically significant differences 

in the proportion of micronucleated polychromatic erythrocytes between mice of all groups including

controls at any sampling time up to 72 hours following exposure up to a very high concentration of 19 

mg/L, illustrating the absence of clastogenicity of the test substance in vivo. In addition, a rat 

micronucleus study conducted with DMG was negative.

No neuropathological changes or effects on the functional observation battery parameters were reported

in any of the studies. The agency does not believe DMEGSA will be neurotoxic.

Chronic/carcinogenicity studies could not be identified for DMEGSA; however, a DEREK evaluation 

for DMG and DMS was conducted and did not show any special alerts. In addition, carcinogenicity

studies were conducted with adipic acid and monosodium succinate in rats and no carcinogenic effects 

were observed. Therefore, the agency does not expect DMEGSA to be carcinogenic in humans. 

Repeated exposures to DMEGSA via inhalation show local effects (likely a result of irritation at the 

point of contact in the nasal region) as well as some changes in hormone levels that, although 

consistently observed, are not considered to be toxicologically significant. The point of departure for the 

risk assessment for chronic oral routes of exposure was from the 14-day oral toxicity study in rats. The 

NOAEL was 842 mg/kg/day and the LOAEL was 1684 mg/kg/day based on reduced weight gain and

food consumption. A 1000 fold uncertainty factor was used for the chronic exposure (10X interspecies 

extrapolation, 10X for intraspecies variability and 10X FQPA factor (See Section 3.4 for more 

information on the FQPA safety factor)). 

Exposure to DMEGSA will be primarily through the oral route of exposure when eating food treated 

with pesticides containing the chemical. In order to estimate the dietary exposure to DMEGSA the 

EPA’s highly conservative I-DEEM model, which incorporates a default drinking water concentration of 

100 ppb, was used. I-DEEM showed the exposure from the use of this inert ingredient in pesticide 

formulations (including exposure through drinking water) would result in acceptable risk to all 
34

subpopulations. The most highly exposed subpopulation was children 1-2 years old at 83.9% of the 

cPAD.

Residential exposure to outdoor pesticide products were evaluated using Agency approved models to 

estimate the risk to residential post-application oral exposures to treated lawns. The dermal study did not 

result in an endpoint of concern therefore dermal exposure was not assessed. . The residential and 

aggregate level of concern (LOC) is for margins of exposure (MOE) that are less than 1000 and is based 

on 10X for interspecies extrapolation, 10X for intraspecies variability, and a10X FQPA safety factor. 

All exposure scenarios resulted in acceptable levels of risk (i.e., MOEs >1000) to all subpopulations 

evaluated. Exposure to DMEGSA inert ingredients via paint, residential antimicrobials, and pet products 

were not evaluated in this risk assessment. When residential and dietary exposures were combined 

exposure did not exceed the acceptable level of risk. 

Occupational exposure would be expected via the dermal and inhalation routes of exposure; however, 

because endpoints of concern were not identified for these routes of exposure in animal studies a 

qualitative occupational assessment was conducted. 

Based on ecological (i.e., fish, invertebrates, and algae) and fate studies the agency concluded that

DMEGSA does not pose an ecological risk to terrestrial or aquatic species. DBE is expected to 

photodegrade when released to air, with a half-life of ranging from 3-24 days. If released to soil, DBE is 

expected to have high mobility through soil and degrade rapidly. If released to water, DBE is not 

expected to volatilize from surface waters or adsorb to suspended solids and sediments in water column, 

but will biodegrade in the presence of bacteria in a matter of days and hydrolyze in a matter of months to 

years depending on pH. Based on the moderate vapor pressure it is believed that these chemicals will be 

moderately volatile and that when released to the atmosphere they will exist primarily in the vapor 

phase. DMEGSA is not expected to persist in the environment and the potential for bioaccumulation is 

low. 

Many of the studies for DMEGSA and DBE showed olfactory effects in rats following inhalation 

exposure. While these effects were observed in rats, it is unlikely that the same effects will be seen in 

humans due to physiological and chemical differences between the species. In addition, some studies 

showed hormonal changes; however, these effects were not seen in other studies and were not 

accompanied by histological changes. 

Based on the evaluated toxicity studies coupled with the expected exposure from the use of these 

chemicals as inert ingredients in pesticide products, EPA concludes that there is a reasonable certainty 

that no harm will result to the general population, including infants and children, from aggregate 

exposure to residues of DMEGSA when used as an inert ingredients in pesticide formulations under 40 

CFR 180.910.
35

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39

Appendix A

US EPA Ver. 3.16, 03-08-d

DEEM-FCID Chronic analysis for INERTS- APG NHANES 2003-2008 2-day

Residue file name: C:\Documents and Settings\dsunderl\My Documents\IDEEM\INERTS_57ACTIVE_100PPBH2OREV.R08

 Adjustment factor #2 NOT used.

Analysis Date 10-29-2013/14:36:37 Residue file dated: 09-26-2013/10:32:39

Reference dose (RfD, Chronic) = .842 mg/kg bw/day

NOEL (Chronic) = 842 mg/kg bw/day

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

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

 Total exposure by population subgroup

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

 Total Exposure

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

 Population mg/kg Margin of Percent 

 Subgroup body wt/day Exposure of RfD 

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

Total US Population 0.189343 4,447 22.5%

Hispanic 0.206762 4,072 24.6%

Non-Hisp-White 0.185800 4,532 22.1%

Non-Hisp-Black 0.175951 4,785 20.9%

Non-Hisp-Other 0.223356 3,770 26.5%

Nursing Infants 0.248204 3,392 29.5%

Non-Nursing Infants 0.459734 1,831 54.6%

Female 13+ PREG 0.165239 5,096 19.6%

Children 1-6 0.546673 1,540 64.9%

Children 7-12 0.227410 3,703 27.0%

Male 13-19 0.133762 6,295 15.9%

Female 13-19/NP 0.135932 6,194 16.1%

Male 20+ 0.140996 5,972 16.7%

Female 20+/NP 0.153162 5,497 18.2%

Seniors 55+ 0.152687 5,515 18.1%

All Infants 0.394428 2,135 46.8%

Female 13-50 0.146403 5,751 17.4%

Children 1-2 0.706242 1,192 83.9%

Children 3-5 0.485634 1,734 57.7%

Children 6-12 0.250554 3,361 29.8%

Youth 13-19 0.134797 6,246 16.0%

Adults 20-49 0.144740 5,817 17.2%

Adults 50-99 0.151788 5,547 18.0%

Female 13-49 0.146333 5,754 17.4%

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