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EXECUTIVE SUMMARY

The Antimicrobials Division (AD) Registration Review Team has evaluated the status 

of the human health assessments for diethylene glycol monomethyl ether (DGME) (case 

5010, PC Code 042204) for the purpose of registration review. DGME is an 

antimicrobial pesticide that is used for non-food uses as an additive in jet fuel, diesel fuel, 

marine fuel, and fuel oil. DGME controls fungi and bacteria in hydrocarbon systems that

can reduce fuel performance. DGME is also a deicer that lowers the freezing point of fuel

thus preventing fuel ice from forming. Fuel ice may form when airplanes fly at higher

elevations. DGME has a use classification as a material preservative (Category VII) and 

only has one registered label, and no tolerances or exemptions from the requirement of a 

tolerance. There are inert uses. However, the inert uses are not covered in this 

assessment.

DGME is formulated as a liquid ready to use product and is sold as a 99.7% active 

ingredient in tanks, drums, and totes. The only potential exposure to DGME is through 

closed mixing and loading into fuel delivery systems. The label prohibits open pouring. 

Closed mixing and loading systems typically use automatic metering pumps using hoses 

and various connecting devices to facilitate transfer from drums, totes, holding tanks, etc.

The purpose of this review is to examine and characterize the existing hazard and 

exposure databases for DGME and to determine whether new data and risk assessments 

are expected to be needed. 

DGME was first registered as a pesticide in June 2002. A Reregistration Eligibility 

Decision (RED) document has not been issued for DGME since this chemical was 

registered after November 1, 1984. The primary source of information for this assessment 

was registration records for the only registered product (EPA Reg. 324-32) and 

applicable Agency risk assessment memoranda pertaining to this registration. 

Based on this review of the Agency data, existing risk assessments, reviews and the 

existing use pattern (e.g., mixing/loading using a closed delivery systems fuel systems), 

the Agency does not expect that data or additional risk assessments will be needed to 

assess occupational, residential, dietary, and drinking water exposures. In addition, the

Agency does not anticipate the need for additional toxicity, exposure, and chemistry

studies to assess the hazards of DGME. 
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Section 1. Chemical Identity

Table 1 Chemical Identity

Common 

Name

Diethylene Glycol Monomethyl Ether 

(DGME)

Synomyms Ethanol, 2-(2-methoxyethoxy) Methyl 

Carbitol

PC Code 042204

CAS registry 

number

111-77-3

Registration 

Review Case 

No.

5010

Structure

Section 2. Toxicology

The Agency has reviewed the existing toxicity assessments and toxicity data for 

DGME. The Agency reviewed the historical toxicological database supporting the 

original registration of DGME. Based on the use pattern (material preservative for fuels)

and application methods (used only in closed systems), the Agency expects that only a 

Tier 1 toxicity data set will be needed. 

Acute Toxicity

For registration review, the Agency will rely on the existing acute toxicity database 

developed during registration. According to Agency documentation (D273299), DGME

has an acute oral toxicity category of IV based on an oral LD50 of 5,050 mg/kg for rats. 

An acute dermal toxicity category of IV was based on a dermal LD50 of 5,050 mg/kg 

from a dermal rabbit study. DGME was not identified as a dermal or eye irritant or a 

dermal sensitizer in rabbits. An inhalation toxicity category of III was assigned based on 

the results of a rat inhalation open literature study (D273299) in which no toxicity was 

identified at the maximum air concentration of 216 ppm (1.06 mg/L).

Mutagenicity

The Agency does not anticipate the need for additional mutagenicity data based on 

review of the existing mutagenicity data submitted during registration of DGME 

(D273300). In the database of mutagenicity studies, no evidence of gene mutation was

identified in an acceptable in vitro bacterial reverse gene mutation (Ames) assay (MRID 

453251-02). This study was considered as acceptable. Another acceptable study, MRID 

453251-03, indicated that no chromosomal aberrations were seen in an in vitro 

mammalian cytogenetics chromosomal aberration study. No statistically significant 

increases of chromosomal aberrations were seen with and without metabolic activation in 
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Chinese hamster ovary CHO-K1 cell cultures. Finally, no statistically significant

increases of micronucleated erthrocytes were seen in an acceptable in vivo mammalian 

cytogenetics bone marrow micronucleus assay in mice (MRID 453251-04).

Subchronic Toxicity 

Dermal

For the initial registration, EPA reviewed a published DGME subchronic dermal 

toxicity study (Hobson et al., 1986: Fund. Appli. Toxicol. 6: 339-348) (D261013). 

Hobson et al. performed a 13-week dermal study in which male guinea pigs received 

DGME dermal doses of 0, 40, 200, or 1000 mg/kg/day for 5 days/week and 6 hours/day. 

Body weight, selected organ weights, hematology, clinical chemistry, urinalysis, and 

gross and histopathologic examinations were observed in this study. A NOAEL of 40 

mg/kg/day was determined based on elevation of urinary calcium, alteration in spleen 

weight, and changes in the mean corpuscular hemoglobin concentration (MCHC) at dose 

levels of 200 mg/kg/day and above (D261013).

Inhalation 

A 90-day inhalation study in male Fisher 344 rats submitted in registration (Miller et 

al. 1985, MRID 44655801) identified no effects on body weights, organ weights, gross 

pathology, histopathology, hematology or serum concentrations up to 216 ppm (1.06 

mg/liter). This concentration was the maximum attainable concentration and was more 

than 60% of the theoretical maximum vapor pressure (U.S. EPA 2002). This study was 

not used to generate inhalation toxicity endpoints for short- and intermediate effects for 

the occupational assessment, since it did not identify a dose response, but the study was 

used for establishing an acute inhalation category.

Developmental Toxicity

EPA reviewed rat and rabbit developmental studies on DiGME (D621013). 

According to this review, Yamano et al. (1993), administered DiGME to Wistar rats at 

dose levels of 0, 200, 600, and 1800 mg/kg/day during days 7-17 of gestation. At 600 

mg/kg, decreased fetal body weight and adverse effect on the fetal thymus were noted in 

the absence of maternal effects. In another rat study by Hardin et al. (1986), Sprague 

Dawley rats were dosed at 0, 720, and 2165 mg/kg. Skeletal abnomalities (reduced 

cranium, reduced skeletal ossification, and rudimentary ribs) and visceral abnormalities 

(dilated renal pelvis) were observed at 720 mg/kg at a dose that was not maternally toxic.

Scortichini et al (1986) dosed pregnant New Zealand rabbits dermally at 0, 50, 250 and 

750 mg/kg during days 6-18 of gestation. No developmental effects were observed but 

maternal effects (reduced body weight) were noticed at the highest dose level.

Summary of Toxicity Data

Based on the review of the registration submissions, the acute toxicity and 

mutagenicity data appear to be satisfied (D273299 and D273300). According to the EPA 

registration submission (D261013), the subchronic dermal study and the dermal 
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developmental data appeared to satisfy the subchronic and developmental data 

requirements. Traditionally, the Agency requires a 90-day inhalation toxicity study to 

assess inhalation toxicity endpoints, but the study was not needed based on the use 

pattern and the label restriction for engineering controls (e.g. closed mixing/loading) that 

will minimize inhalation exposure. Additionally, the Agency also indicated some concern 

based on the developmental effects and that a 2-generation reproductive study may be 

needed. However, the 2-generation reproductive study will not be needed since DGME 

is only used for non-food uses. New uses or new registrations in the future could 

potentially trigger the need for these toxicity data considerations in the future.

Section 3. Dietary Assessment

Currently, there is only one registered label for the active ingredient, and no 

tolerances or exemptions from the requirement of a tolerance. No residue data are 

needed and no dietary exposures of concern are anticipated based on the use pattern

of DGME.

Section 4. Aggregate and Cumulative Exposure

In examining aggregate exposure, EPA takes into account the available and reliable 

information concerning exposures to pesticide residues in food and drinking water, and 

non-occupational pesticide exposures. Dietary (food and drinking water) exposures of 

concern are not anticipated for DGME. An aggregate risk assessment for DGME is not 

needed since there is no dietary or residential exposure for the active ingredient. 

Therefore, an aggregate assessment is not needed.

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to 

establish, modify, or revoke a tolerance, the Agency consider "available information” 

concerning the cumulative effects of a particular pesticide's residues and "other 

substances that have a common mechanism of toxicity.” EPA has not yet determined 

whether DGME has a common mechanism with other compounds, consequently a 

cumulative assessment will not be performed at this time.

Section 5. Occupational/Residential Exposure

An occupational and/or residential exposure assessment is required for an active 

ingredient if (1) certain toxicological criteria are triggered and (2) there is potential 

exposure to handlers (mixers, loaders, applicators, etc.) during use or to persons entering 

treated sites after application is complete. There are no potential residential exposures

and minimal exposures to persons entering treated sites so a residential risk assessment is 

not needed.

DGME is an antimicrobial pesticide used on indoor nonfood uses as a fuel additive in 

occupational settings only. The label prohibits mixing or loading of DGME with any fuel 

unless it is done through closed delivery systems. These systems typically use automatic 

metering pumps using hoses and various connecting devices to facilitate transfer from 

drums, totes, holding tanks, etc. According to data from the supplier, the closed system 

process begins at “pickup” from the supplier. The additive, in bulk, is loaded into the 
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railroad tank cars or tank trucks through closed piping or hose systems. The bulk is 

delivered at a gasoline terminal where it is transferred through closed mixing to a holding 

tank. When an order is made additive is metered into the fuel of a tank truck at a rate of 

0.1-0.15% by weight, as it is loaded (US EPA, 2002). 

An occupational assessment was conducted in 1999 (D261014) and the calculated 

MOEs were acceptable for handlers (e.g., closed mixing/loading worker exposure).

Potential for postapplication exposures (e.g., exposure to persons entering treated sites 

after application is completed) is expected to be minimal based on the engineering 

controls. EPA expects dermal and inhalation handler exposures will likely be minimized

using a closed delivery system. In addition, the label specifies that the appropriate 

personal protective equipment (PPE) [e.g. chemical resistant gloves, long sleeved shirt, 

socks, shoes, and pants] will be used for handling exposures such as connecting hoses or 

maintenance of the closed system. Because of the safety requirements (PPE) and 

engineering controls specified on the label, an additional occupational risk assessment is 

anticipated as not needed. No additional exposure data are needed for the closed mixing 

fuel additive use. Product use data was already provided in the original submission, so it 

is not anticipated as needed.

Section 6. Anticipated Data Needs

The Antimicrobial Division (AD) does not anticipate the need for any additional 

human health data needs for DGME at the current time. New uses or new registrations in 

the future could potentially trigger the need for these toxicity data considerations in the 

future, however. 

Section 7. Tolerances

There are no tolerances or exemptions from the requirement of tolerance for DGME.

Section 8. Endocrine Disruption

As required under FFDCA section 408(p), EPA has developed the Endocrine 

Disruptor Screening Program (EDSP) to determine whether certain substances (including 

pesticide active and other ingredients) may have an effect in humans or wildlife similar to 

an effect produced by a “naturally occurring estrogen, or other such endocrine effects as 

the Administrator may designate.” The EDSP employs a two-tiered approach to making 

the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays 

to identify the potential of a chemical substance to interact with the estrogen, androgen, 

or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening 

and are found to have the potential to interact with E, A, or T hormonal systems will 

proceed to the next stage of the EDSP where EPA will determine which, if any, of the 

Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to 

identify any adverse endocrine related effects caused by the substance, and establish a 

dose-response relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data call-ins for 

the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert 
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ingredients. This list of chemicals was selected based on the potential for human 

exposure through pathways such as food and water, residential activity, and certain postapplication agricultural scenarios. This list should not be construed as a list of known or 

likely endocrine disruptors.

DGME is not among the group of 58 pesticide active ingredients on the initial list to 

be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all 

pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data 

call-ins for all pesticide active ingredients. 

For further information on the status of the EDSP, the policies and procedures, the list 

of 67 chemicals, the test guidelines and the Tier 1 screening battery, please visit our 

website: http://www.epa.gov/endo/.

Section 9. Human Incident Data

There have been no human incidents reported in any of the OPP databases associated 

with exposure to DGME as a fuel additive. 

Section 10. Overall Conclusions

The Agency reviewed the hazard and exposure databases for DGME and anticipates 

that no additional studies will be needed for registration review. The Agency does not 

expect to conduct any additional risk assessments for this chemical since this use was 

already assessed in registration. EPA also expects the exposure to be minimal based on 

engineering controls typically used for fuel additive use. New uses or new registrations 

could potentially trigger the need for additional risk assessments and toxicity data 

considerations in the future, however.

Section 11. References

US EPA, 2002. Memorandum from F. Sanders, Antimicrobials Division Director to M. 

Mulkey, Office of Pesticide Programs Director. Subject: 12-Month Time Limited 

Registration of Diethylene Glycol Monomethyl Ether. Antimicrobials Division (AD), 

Office of Pesticide Programs (OPP). June 2002.

D261013. Memorandum from T. McMahon, Senior Toxicologist, Risk Assessment 

Science Support Branch (RASSB) to D. Edwards, Branch Chief, Regulatory 

Management Branch 1 (RMB1). Subject: Diethylene Glycol Monomethyl Ether 

(DGME). Review of Literature Data in Support of Jet Fuel De-Icer Use. Antimicrobials 

Division (AD), Office of Pesticide Programs (OPP). November 1999.

D261014. Memorandum from S. Mostaghimi, Environmental Engineer, Risk 

Assessment Science Support Branch (RASSB) to W.Dang, Team Leader, Risk 

Assessment Science Support Branch (RASSB). Occupational Exposure Assessment 

Estimates of Diethylene Glycol Monomethyl Ether. Antimicrobials Division (AD), 

Office of Pesticide Programs (OPP). December 1999.
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D273299. Memorandum from C. Jiang, Chemist, RASSB to M.Swindell, Team Leader, 

RMB1. Subject:Acute Toxicity Reviews. Phillips Fuel Additive. Antimicrobials Division 

(AD), Office of Pesticide Programs (OPP). April 2001.

D273300. Memorandum from S. Malish, Toxicologist, RASSB to M.Swindell, Team 

Leader, RMB1. Subject: Toxicity Reviews of Mutagenicity Studies. Phillips Fuel 

Additive. Antimicrobials Division (AD), Office of Pesticide Programs (OPP). August 

2001.