U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### Supporting Documents for Initial Risk-Based Pr ioritization of High Production Volume

Chemicals

Chemical/Category: CAS No. 110-71-4, Ethane, 1,2-dimethoxy- (also known as 1,2- Dimethoxyethane, or Monoglyme)

Contents:

• Page 2: Screening-Level Risk Characterization, 3/13/2008

• Page 6: Screening-Level Hazard Characterization, 2/22/2008

• Page 21: Screening-Level Exposure Characterization, 3/14/2008U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 2 QUALITATIVE SCREENING-LEVEL RISK CHARACTERIZATION FOR 1, 2-Dimethoxyethane (CAS No. 110-71-4) (Monoglyme)

1. Background

The High Production Volume (HPV) Challenge Program 1 is a voluntary initiative aimed at developing and making publicly available screening-level health and environmen tal effects information on ch emicals manufactured in or imported into the United States (U.S.) in quantities greater than one million pounds per year. In the Challenge Program, producers and importers of HPV chemicals volun tarily sponsor chemicals; sponsorship entails the identification and initial assessment of the adequacy of ex isting toxicity data/information, conducting new testing if adequate data do not exist, and making both new and existing data and information available to the public. Each complete data submission contains data on 18 internationally agreed to “SIDS” (Screening Information Data Set Error!

Bookmark not defined. ,2 ) endpoints that are screening-level indicators of potential hazards (toxicity) for humans or the

environment and environmental fate.

The Environmental Protection Agency’s Office of Pollution Prevention and Toxics (OPPT) is evaluating the data submitted in the HPV Challenge Program on approximately 1,400 sponsored chemicals. Data submitted to the Organisation for Economic Co-operation and Development (OECD) HPV Programme are also being evaluated. OPPT developed a screening-level hazard characterization that consists of an obj ective evaluation, conducted according to established EPA guidance Error! Bookmark not defined. ,3 , of the quality and completeness of the data set provided and is based primarily on hazard data provided by sponsors. The characterization does not draw conclusions regarding the completeness of all data generated with respect to a specific chemical substance or mixture. The OECD SIDS documents (SIDS Initial Assess ment Profile; SIAP and SIDS Initial Assessment Report; SIAR) provide similar information. Under both the HPV Challenge and OECD HPV Programs, chemicals that have similar chemical structures, properties and biological activities may be grouped together and their data shared across the resulting category. Evaluation of chemical category formation and da ta extrapolation(s) among category members is performed in accor d with established U.S. EPA 1 and OECD 4 guidance.

In 2006 and 2007, EPA received data on uses of and r easonably likely exposures to chemicals on the Toxic Substances Control Act (TSCA) Inventory of existing chem icals, submitted in accordance with the requirements of the Inventory Update Reporting (IUR) rule 5 . Information is collected every five years under IUR, promulgated under the authority of section 8(a) of TSCA. The most recent reports pertain to chemicals manufactured in (including imported into) the U.S. during calendar year 2005 in quantities of 25,000 pounds or more at a single site. Information is reported on the identity of the chemical manufactured or imported and the quantity, physical form, and number of persons reas onably likely to be exposed during manuf acture of the chemical. For chemicals manufactured or imported in quantities of 300,000 pounds or more at a single site during calendar year 2005, additional information was reported on the industrial proce ssing and uses of the chemical, the number of industrial processing sites and of employees reasonably likely to be ex posed to the chemical at these sites, the consumer and

commercial uses of the chemical and an indication whether the chemical is used in products intended for use by children under 14 years of age.

For these qualitative screening-level risk characterization documents, EPA has reviewed the IUR data to evaluate exposure potential. In addition, exposure information th at may have become available through prior Agency actionshas been considered, as appropriate. The resulting exposure information has been combined with the screeninglevel hazard characterizations to develop this qualitative screening-level risk characterization 6,7 . These screeninglevel risk characterizations are technical documents intended to support subsequent decisions and actions by OPPT.

1 U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm

. 2 U.S. EPA. HPV Challenge Program – Information Sources; http://www.epa.gov/chemrtk/ pubs/general/guidocs.htm

. 3 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm

. 4 OECD. Guidance Document on the Development and Use of Chemical Categories; http://www.oecd.org/docum ent/7/0,2340,en_2649_34379_1947463_1_1_1_1,00.html

. 5 U.S. EPA – Basic IUR Information: http://www.epa.gov/opptintr/iur/pubs/ guidance/basic-information.htm

6 U.S. EPA Guidelines for Exposure Assessment; http://cfpub.epa.gov/ncea/r af/recordisplay.cfm?deid=15263

7 U.S. EPA. Risk Characterization Program; http://www.epa.gov/osa/spc/2riskchr.htm

.U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 3 Accordingly, the document is not written with the goal of informing the general public. The purpose of the qualitative screening level risk characterizations is two-fold : to support initial risk-based decisions to prioritize chemicals and inform risk management options and to identify data needs for individual chemicals or chemical categories.

2. Supporting Chemical Justification

The sponsor submitted data for additio nal chemicals to support characterization of some hazard endpoints for the HPV chemical 1,2-dimethoxyethane, or monoglyme. The supporting chemicals are 1,3-dioxolane (CAS No. 646- 06-0) for the aquatic toxicity endpoints and 2-methoxyethanol (CAS No. 109-86-4) for the human health toxicity endpoints. EPA accepted the use of 1,3-dioxalane as a su pporting chemical for aquatic toxicity because it is similar to monoglyme in terms of ch emical class (neutral organic/diethe r) and it has a similar octanol-water partition coefficient. For the human health endpoints, 2- methoxyethanol is a major metabolite of monoglyme in mammals. Thus, EPA agrees that these chem icals are appropriate analogs for monoglyme.

3. Physical-Chemical Propertie s and Environmental Fate

This report was prepared using the best available data from a number of sources, but draws no conclusions regarding whether additional relevant data may exist. Monoglyme is a liquid at room temperature. It has high water solubility and high vapor pressure. It is highly mobile in soil, does not bioaccumulate, and does not hydrolyze under environmental pHs. Biodegradation is expected to be slow. In the atmosphere, it is expected to photodegrade within slightly over one day. Based on these findings, monoglyme is expected to be moderately persistent (P2) and the bioaccumulation potential for monoglyme is ranked low (B1) based on its estimated bioconcentration factor (BCF) of 3.

4. Hazard Characterization

Aquatic Organism Toxicity. The potential aquatic toxicity of monoglyme was assessed using data from the analog 1, 3-dioxolane (CAS No. 646-06-0). The evaluation of available aquatic toxicity data on the analog suggests that the potential acute hazard for fish, aquatic inve rtebrates and aquatic plants is low.

Human Health Toxicity. The acute toxicity of monoglyme is low via oral, dermal and inhalation routes of exposure. The potential toxicity from repeated exposure to monoglyme was assessed using a major metabolite, 2- methoxyethanol (CAS No. 109-86-4). In laboratory animals, repeated exposure to 2-methoxyethanol results in testicular degeneration and adverse effects on the process of blood cell formation. The thymus and adrenal gland are also potential targets of toxicity. The metabolism of m onoglyme to 2-methoxy acetic aci d, which interferes with sperm production, can lead to adverse effects on reproduction. Developmental toxicity studies with monoglyme in laboratory animals indicate adverse effects on fetal body we ight, skeletal structure and survival. Several genetic toxicity studies with monoglyme are available. Monoglyme was positive for causing gene mutations in bacteria. In mammalian cells, monoglyme did not show a potential to induce gene mutations, but did induce sister chromatid exchanges (SCE) and chromosomal aberrations. The potential health hazard of monoglyme is high based on the results of the repeated-dose (effects on blood, thymus, adrenal gland, and testicular degeneration) and developmental (increased fetal death and skeletal eff ects and decreased fetal body weight) toxi city studies at relatively low doses. Available data also suggest that monoglyme has the potential to be genotoxic.

5. Exposure Characterization

This exposure characterization was completed using available 2006 Inventory Update Rule (IUR) submissions.

Data and information that are claimed Confidential Business Information (CBI) by the submitter were reviewed and considered by EPA in preparing this assessment but are not disclosed in this summary.

In addition, the following sources were reviewed to id entify exposure and use information: the HPV Challenge Submissions, OECD SIDS Data, the Toxics Release Inventory (TRI), OSHA PEL documentation, various databases and public sources.U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 4 1, 2-Dimethoxyethane was manufactured and/or imported in the United States in amounts ranging from 1,000,000 to 10,000,000 pounds in 2005. The HPV submission indicates th at the chemical is used pr imarily as an industrial solvent, process aid and as a component of lithium batteries and industrial coatings.

Exposure to Workers The National Occupational Exposure Survey (NOES), conduc ted between 1981 and 1983 estimated a total of 3319 workers potentially exposed to this chemical (NIOSH, 2007b). Based on IUR reporting, the maximum total number of workers likely to be exposed to this chemical during manufacturing and industrial processing and use is less than 100. There may be additional potentially exposed workers that are not included in this estimate since not all production volume has been accounted for, and there is at least one use that contains a "Not Readily Obtainable" (NRO) response among the submissions. This chemical has a vapor pressure of 48 torr at 20°C. OPPT has established 0.001 torr as a value above which worker exposures to vapors should be estimated for chemical assessments. Therefore, this chemical’s vapor pressure could result in significant worker exposures to vapors if workers are close to the liquid. This chemical does not have an OSHA Permissible Exposure Limit.

The IUR-based ranking for worker exposure is high.

Exposures to General Population and the Environment The chemical is not on the Toxics Release Inventory. Based on use information, EPA assumes for the purpose of this risk prioritization that there is potential for exposure s to the general population and the environment. The IURbased ranking for general population and the environment is high due to the assumption that there will be exposure

to this chemical.

Exposure to Commercial Workers and Consumers Non-CBI IUR information indicates potential exposure to monoglyme for commercial workers and consumers. Based on its vapor pressure as cited above, there could be significant worker exposures to vapors if workers are near products containing this chemical. Information provided also suggests that monoglyme will be used in consumer products. The IUR-based ranking for commercial workers and consumers is high due to the assumption that monoglyme is used in commercial worker/consumer products.

Exposure to Children Information provided suggests that monoglyme will be used in commercial/consumer products, including children’s products. The IUR-based ranking for children’s exposure to monoglyme is high due to the assumption it is used in products intended for use by children.

6. Risk Characterization

The statements and rationale provided below are intended solely for the purpose of this screening-level and qualitative risk characterization and will be used for prio ritizing substances for future work in the U.S. HPV Challenge Program.

6.1. Risk Statement and Rationale

Potential Risk to Aquatic Organisms from Environmental Releases ( LOW CONCERN): EPA assumes there is potential for exposure to aquatic organisms from environmental releases. Although monoglyme is considered moderately persistent in the environment, it has a lo w acute aquatic toxicity h azard, which suggests a low concern for potential risk to aquatic organisms from environmental releases.

Potential Risk to the General Population from Environmental Releases (MEDIUM CONCERN): EPA assumes there is potential for exposure to the general population from environmental releases. Monoglyme is considered to be moderately persistent in the environment. The hi gh concern for hazard to human health (at relatively low doses in animal studies) combined with potential exposure s suggests a medium concern for potential risk to the general population from environmental releases.U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 5 Potential Risk to Workers (HIGH CONCERN): Available IUR data indicate that workers are likely to be exposed to monoglyme. The high concern for hazard to human health (at relatively low doses in animal studies) combined with the likely exposures that occur in the occupational setting suggests a high concern for potential risk to workers.

Potential Risk to Commercial Workers and Consumers from Known Uses (HIGH CONCERN): Available IUR

data indicate that commercial workers and consumers will be exposed to monoglyme. The high concern for hazard to human health (at relatively low doses in animal studies) combined with the possible exposures that occur in commercial worker and consumer use settings sugg ests a high concern for potential risk to both groups.

Potential Risk to Children from Possible Use of Products with Monoglyme (HIGH CONCERN): Available IUR data indicate that children are exposed to monoglyme. The high concern for hazard to human health is important in the case of children’s health because animal studies indicate this chemical is toxic to developing organisms at relatively low doses in animal studies. Therefore, the high hazard concerns combined with possible exposures suggest a high concern for potential risk to children.

6.2. Uncertainties

Monoglyme may have minor uses that were not reported in IUR.

6.3. Data Needs

No data needs have been identified at this time.U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 6 SCREENING-LEVEL HAZARD CHARACTERIZATION

FOR HIGH PRODUCTION VOLUME CHEMICALS

SPONSORED CHEMICAL

1,2-Dimethoxyethane (CAS No. 110-71-4)

[9 th 

### CI Name: Ethane, 1,2-dimethoxy-]

SUPPORTING CHEMICALS

1,3-Dioxolane (CAS No. 646-06-0) 2-Methoxyethanol (CAS No. 109-86-4)

August 2007

Revised: February 2008

Prepared by

High Production Volume Chemicals Branch

Risk Assessment Division

and Exposure Assessment Branch Economics, Exposure and Technology Division

Office of Pollution Prevention and Toxics Environmental Protection Agency

1200 Pennsylvania Avenue, NW

Washington, DC 20460-0001U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 7 SCREENING-LEVEL HAZARD CHARACTERIZATION

OF HIGH PRODUCTION VOLUME CHEMICALS

The High Production Volume (HPV) Challenge Program 8 is a voluntary initiative aimed at developing and making publicly available screening-level health and environmen tal effects information on ch emicals manufactured in or imported into the United States in quantities greater than one million pounds per year. In the Challenge Program, producers and importers of HPV chemicals voluntarily sponsor chemicals; sponsorship entails the identification and initial assessment of the adequacy of existing toxicity data /information, conducting new testing if adequate data do not exist, and making both new and existing data and information available to the public. Each complete data submission contains data on 18 internationally agreed to “SIDS” (Screening Information Data Set Error! Bookmark not

defined. ,9 ) endpoints that are screening-level in dicators of potential hazards (toxicity ) for humans or the environment.

The Environmental Protection Agency’s Office of Pollution Prevention and Toxics (OPPT) is evaluating the data submitted in the HPV Challenge Program on approximately 1, 400 sponsored chemicals. OPPT is using a hazardbased screening process to prioritize review of the submissions. The hazard-based screening process consists of two tiers described below briefly and in more detail on the Hazard Characterization website 10

.

Tier 1 is a computerized sorting proce ss whereby key elements of a submitted data set are compared to established criteria to “bin” chemicals/categories for OPPT review. This is an automated process performed on the data as submitted by the sponsor. It does not include evaluation of the quality or completeness of the data.

In Tier 2, a screening-level hazard characterization is developed by EPA that consists of an objective evaluation of the quality and completeness of the data set provided in the Challenge Program submissions. The evaluation is performed according to established EPA guidance Error! Bookmark not defined. ,11 and is based primarily on hazard data provided by sponsors. EP A may also include additional or upda ted hazard information of which EPA, sponsors or other parties have become aware. The hazard characterization ma y also identify data gaps that will become the basis for a subsequent data needs assessm ent where deemed necessary. Under the HPV Challenge Program, chemicals that have similar chemical structures, pr operties and biological activities may be grouped together and their data shared across the resulting category. This approach often significantly reduces the need for conducting tests for all endpoi nts for all category members. As part of Tier 2, eval uation of chemical category rationale and composition and data ex trapolation(s) among category memb ers is performed in accord with

established EPA Error! Bookmark not defined. and OECD 12 guidance.

The screening-level hazard characteriza tions that emerge from Tier 2 are important contributors to OPPT’s existing chemicals review process. These hazar d characterizations are technical docume nts intended to s upport subsequent decisions and actions by OPPT. Accordingly, the documents are not written with the goal of informing the general public. However, they do provide a vehicle for public access to a concise asse ssment of the raw technical data on HPV chemicals and provide information previously not readily available to the public. The public, including sponsors, may offer comments on th e hazard characterization documents.

The screening-level hazard characterizations, as the name i ndicates, do not evaluate the po tential risks of a chemical or a chemical category, but will serve as a starting point for such reviews. In 2007, EPA received data on uses of and exposures to high-volume TSCA existing chemicals, submitted in accordance with the requirements of the Inventory Update Reporting (IUR) rule. For the chemi cals in the HPV Challenge Pr ogram, EPA will review the IUR data to evaluate exposure potential. The resulting exposure information will then be combined with the screening-level hazard characterizations to develop screening-level risk characterizations 4,13 . The screening-level

risk characterizations will inform EPA on the need for furt her work on individual chemicals or categories. Efforts are currently underway to consider how best to utilize these screening-level risk characterizations as part of a risk-

8 U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm

. 9 U.S. EPA. HPV Challenge Program – Information Sources; http://www.epa.gov/chemrtk/ pubs/general/guidocs.htm

. 10 U.S. EPA. HPV Chemicals Ha zard Characterization website ( http://www.epa.gov/hpvis/abouthc.html ).

11 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm

. 12 OECD. Guidance on the Development and Use of Chemical Categories; http://www.oecd.org/dataoecd/60/47/1947509.pdf

. 13 U.S. EPA. Risk Characterization Program; http://www.epa.gov/osa/spc/2riskchr.htm

.U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 8 based decision-making pr ocess on HPV chemicals which applies the resu lts of the successful U.S. High Production Volume Challenge Program and the IUR to support judgments concerning the need, if any, for further action.



### SCREENING-LEVEL HAZARD CHARACTERIZATION 1,2-Dimethoxyethane (CAS No. 110-71-4)

Introduction

The sponsor, Ferro Corporation, submitted a Test Plan and Robust Summaries to EPA for 1,2-Dimethoxyethane (CAS Number 110-71-4; 9 th CI name: ethane, 1,2-dimethoxy-), or monoglyme, on December 27, 2001. EPA posted the submission on the ChemRTK HPV Challenge Website on January 3, 2002 ( http://www.epa.gov/chemrtk/pubs/summaries/dimetho/c13455tc.htm ). EPA comments on the original submission were posted to the website on July 3, 2002. Public comments were also received and posted to the website. The sponsor submitted updated/revised documents on August 27, 2002, which were posted to the ChemRTK website on September 5, 2002.

This screening-level hazard characterizati on is based primarily on the review of the test plan an d robust summaries of studies submitted by the sponsor(s) under the HPV Challe nge Program. In preparing the hazard characterization, EPA considered its own comments and public comments on the original submission as well as the sponsor’s responses to comments and revisions made to the submission. Summary tables of SIDS endpoint data are provided herein and the structure(s) of the chemical(s) are provided in the ap pendix. The screening-level hazard characterization for environmental and human health toxicity is based largely on SIDS endpoints and is described according to established EPA or OECD effect le vel definitions and hazard assessment practices.

Supporting Chemical Justification

The sponsor submitted data for additional chemicals to s upport characterization of some endpoints. The supporting chemicals are: 1,3-dioxolane (CAS No. 646-06-0) and 2- methoxyethanol (CAS No. 109-86-4). EPA agrees that these chemicals are appropriate analogs for monoglyme. Chemical structures are provided in the data table in the Appendix.

Summary-Conclusion

Monoglyme is a liquid at room temperature. It has high wate r solubility and high vapor pressure. It is highly mobile in soil, does not bioaccumulate, and does not hydrolyze under environmental pHs. Biodegradation is expected to be slow. In the atmosphere, it is expected to photodegrade within slightly over one day. Based on these findings, monoglyme is expected to be moderately persistent (P2) and the bioaccumulation potential for monoglyme is ranked low (B1) based on its estimated bioconcentration factor (BCF) of 3.

The evaluation of available aquatic toxicity data on supporting chemicals (primarily 1,3-dioxalane) for fish, aquatic invertebrates and aquatic plants indicates that the potential acute hazard of monoglyme to aquatic organisms is low.

The acute toxicity of monoglyme is low via oral, dermal and inhalation routes of exposure. Repeated-dose studies with monoglyme have not been conducted. However, detailed information on the metabolic pathway of monoglyme justifies the use of 2-methoxyethanol, a major metabolite of this chemical, as a supporti ng chemical for assessing the repeated-dose toxicity of monoglyme. In 13-week drinking water studies of 2-methoxyethanol, testicular degeneration and adverse effects on hematopoiesis were seen in both rats and mice. Additional target organs in these studies were the thymus in rats and adrenal gland in mice. Adverse effects to reproduction are based on metabolism of monoglyme to 2-methoxy acetic acid, which interferes with sperm production. In a screening test performed by the National Toxicology Program (NTP), no viable pups were delivered from mice given single oral doses of monoglyme during days 7 through 14 of gestation. Body weight loss was seen in treated dams. The following effects were observed in oral developmental toxicity studi es: increased numbers of stillborn pups, fetal edema, and increased gestation length in rats and decreas ed fetal body weight and skeletal defects in mice. Increases in gene mutations were observed in bacterial ce lls without metabolic activation, but not when metabolic activation was present. In mammalian cells, monoglyme did not show potential to induce gene mutations, but didU.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 9 induce sister chromatid exchanges (S CE) and chromosomal aberrations.

The potential health hazard of monoglyme is high based on the results of the repeated-dose (blood, thymus, adrenal gland, and testicular degeneration) and developmental (increased fetal death and skeletal effects and decreased fetal body weight) toxicity studies at relatively low doses in animal studies. Available data indicate monoglyme has the potential to be genotoxic.

No data gaps were identified under the HPV Challenge Program.

1. Physical-Chemical Properties and Environmental Fate

This report was prepared using the best available data from a number of sources, including information from the HPV test plan and robust summaries (Ferro, 2001), the Hazardous Substance Data Bank (HSDB, 2007) and estimations using EPI Suite TM (U.S. EPA, 2007).

Basic physical-chemical and environmental fate properties of monoglyme are listed in Tables 1a and 1b, respectively.

Physical-Chemical Properties Characterization Monoglyme is a liquid at room temperature and has bot h high water solubility and a high vapor pressure.

Environmental Fate Characterization Monoglyme will mainly exist in the vapor phase in the atmo sphere because of its high vapor pressure. In the atmosphere, monoglyme has an estimated half-life of 25 hours due to photooxidation with hydroxyl radicals. Environmental fate information for monoglyme indicates that it is highly soluble in water. Volatilization of monoglyme may be possible from dry soil surfaces, based on its vapor pressure, but will be low from moist soil and water surfaces based on an estimated Henry's Law constant. It is highly mobile in soil, does not bioaccumulate, and does not hydrolyze under environmental pHs. Biodegradation is judged to be slow. Limited data, based on enrichment and pure culture studies, suggest that this compound may be resistant to biodegradation in both soil and water. This inference is supported by data for several ether analogs. Therefore, monoglyme is expected to be moderately persistent (P2). Bioaccumulation potential is ranked low (B1) based on its estimated BCF of 3It will have high mobility in soil. The estimated BCF value indicates it will not tend to bioaccumulate.

Table 1a. Physical-Chemica l Properties of MonoglymeU.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 10 Structure O

O

Property Value/Descriptor 1

CAS No. 110-71-4

IUPAC monoglyme

MW 90.12

Physical State colorless liquid

Melting Point -58°C (m)

Boiling Point 82-83°C (m)

Vapor Pressure 48 mm Hg @ 20°C (m)

Water Solubility 1x10 +6 mg/L (m)

Density 0.863 @ 20/4°C

Log Kow -0.21

1 (m) denotes measured values and all values are from Ferro (2001).U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 11 Table 1b. Environmental Fate Characteristics of Monoglyme

Property Value/Descriptor 1 Reference

Photodegradation Half life = 25 hours (c alculated) Ferro 2001 & US EPA 2007

Aerobic Degradation No biodegradation over 33 weeks (m) Ferro 2001 & HSDB 2007

hydrolysis No information

Bioaccumulation BCF = 3

Henry’s Law

Constant 1.1x10 -6 atm-cu m/mole

Photolysis Not significant

K
oc 18 (calculated) Ferro 2001 & HSDB 2007

Fugacity Air 0.82-2.32%, Water 47.8-63.3%, Soil 35.8- 50.2%, sediment <0.14% (Level III) Ferro 2001 & US EPA 2007

Persistence P2 (moderate)

Bioaccumulation B1 (low) FR 1999

1 

### ( m ) denotes measured value

2. Environmental Effects – Aquatic Toxicity

Because no adequate data were available on monoglyme, EPA accepted the use of 1,3-dioxalane as a supporting chemical for aquatic toxicity because it is similar to monoglyme in terms of ch emical class (neutral organic/diether) and similar octanol-water partition coefficient. In addition, ECOSAR estimations for both compounds suggest low and similar toxicity. All data presented below are from the submission by the sponsor (Ferro, 2001) unless

otherwise noted.

Acute Toxicity to Fish

1,3-Dioxolane (CAS No. 646-06-0, supporting chemical) Bluegill sunfish ( Lepomis macrochirus ) were exposed to 0 or 95.4 mg/L of supporting chemical, 1,3-dioxolane (measured concentration), for 96 hours under static-renewal conditions. No fish died during the exposure period.

No sub-lethal effects of the test substance were observed.

96-h LC 50 > 95.4 mg/L

Acute Toxicity to Aquatic Invertebrates

1,3-Dioxolane (CAS No. 646-06-0, supporting chemical) (1) Daphnia magna were exposed to measured concentrations of 0, 213, 411 or 772 mg/L of supporting chemical, 1,3-dioxolane, for 48 hours under static-renewal conditions. There was no mortality. No immobilization was seen at 24 hours in control or treated groups. At 48 hours, 0/20, 8/20, 6/20 and 9/20 daphnia were immobilized at 0, 213, 411 and 772 mg/L, respectively. Based on the lack of mort ality and the lack of a concentration-dependent response, it appears that the stress of the renewal conditions may have contributed to the immobilization.

24-h EC 50 > 764 mg/L

48-h EC 50 > 772 mg/L (highest concentration tested)U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 12 2-methoxyethanol (CAS No. 109-86-4, supporting chemical) (2) Daphnia magna were exposed to supporting chemical 2-methoxyethanol for 24 hours in a static test (no other details were provided).

24-h EC 50 > 10,000 mg/L

Toxicity to Aquatic Plants

1,3-Dioxolane (CAS No. 646-06-0, supporting chemical) (1) Green algae ( Pseudokirchneriella subcapitata ) were exposed to measured concentrations of 0 (<31.0), 36.9, 81.0, 163, 280 or 877 mg/L of supporting chemical, 1,3-dioxolane. After 72 hours, the percentage cell growth inhibition compared to the control was 19% at 877 mg/L. There was no significant sta tistical difference between the algal growth of the control and test solutions.

72-h EC 50 (biomass) > 877 mg/L (highest measured concentration)

72-h EC 50 (growth) > 877 mg/L

(2) A standard toxicity test for aquatic plants was not provided for monoglyme. A 96-hour EC 50 for green algae, estimated by ECOSAR, was provided to evaluate the plant toxicity of monoglyme.

96-h EC 50 = 4043 (estimated)

Conclusion: The evaluation of available aquatic toxicity data on supporting chemicals for fish, aquatic invertebrates and aquatic plants indicates that the pote ntial hazard of monoglyme to aquatic organisms is low.

3. Human Health Effects

Acute Oral Toxicity

Monoglyme (CAS No. 110-71-4) Female rats (4/group) were administered monoglyme via oral gavage at doses of 500, 1000, 2000 or 4000 mg/kg-bw and observed for 14 days. No mortality was seen; however, at 2000 and 4000 mg/kg-bw rats were unbalanced and lethargic after treatment. All surviving animals gained weight during the observation period. There were no abnormal findings during necropsy.

LD 50 > 4000 mg/kg-bw

Acute Inhalation Toxicity

Monoglyme (CAS No. 110-71-4) Rats (sex and number/group not specified) were administered monoglyme via whole-body vapor inhalation of 20 or 63 mg/L of for 6 hours and observed for 14 days. Exposure to 20 mg/L produced signs of irritation and slight ataxia. None of the animals died and all gained weight normally during the observation period. Rats exposed to 63 mg/L showed signs of irritation at the beginning of exposure, progressed to prostration after 1.5 hours and remained prostrate until the 6-hour exposure was terminated. Although all of the animals survived during the 6-hour exposure to 63 mg/L, all of them died within 72 hours post-exposure. 20 mg/L < LC 50 < 63 mg/L

Acute Dermal Toxicity

Monoglyme (CAS No. 110-71-4) Female rabbits (2/group) were administered dermal doses of monoglyme at 1000 or 2000 mg/kg-bw and observed for 14 days. Rabbits at the 1000 mg/kg-bw level appeared healthy and gained weight during the observation period. One of the two rabbits in the high-dose group died.

LD 50 = 1000 - 2000 mg/kg-bw

Repeated-Dose ToxicityU.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 13 2-Methoxyethanol (CAS No. 109-86-4, supporting chemical) (1) Male and female rats (10/sex/dose) were administered supporting chemical, 2-methoxyethanol, in drinking water at concentrations of 0, 750, 1500, 3000, 4500 or 6000 ppm (70-800 mg/kg-bw/day) over a 13-week period. Mortality was observed at 4500 and 6000 ppm in males and females. Dose-related decreases in body weight gain were reported. Testicular degeneration in males and decreased thymus weights in males and females occurred at the lowest concentration. Treatment-related histopathology changes were observed in the testes, thymus andhematopoietic tissues (spleen, bone marrow and liver). Higher doses produced a progressive anemia. A doserelated degeneration of the germinal epithelium in the semini ferous tubules of the testes was observed. In special stop-exposure studies in male rats, in which administration of 2-methoxyethanol was stopped after 60 days, marked degeneration of the seminiferous tubules was present in rats treated with 3000 ppm and mild to moderate degeneration was observed in rats treated with 1500 ppm. LOAEL = 750 ppm (approximately 70 mg/kg-bw/day; based on testicular degeneration in males and decreased thymus weights in both sexes )

NOAEL = Not established

(2) Male and female mice (10/sex/dose) were administered supporting chemical, 2-methoxyethanol, at doses of 0, 2000, 4000, 6000, 8000 or 10,000 ppm (300 to 1800 mg/kg-bw/day) daily in drinking water over a 13-week period. 2-methoxyethanol produced dose-related effects on the testes (4000 ppm and above), spleen and adrenal gland (females only). A dose-related degeneration of the germinal epithelium in seminiferous tubules of the testes was observed. A dose-related increase in splenic hematopoiesis was more prominent. 2-Methoxyethanol caused prominent lipid vacuolization of the X-zone of the adre nal gland in female mice. A NOAEL was not achieved for females since adrenal gland hypertrophy and increased he matopoiesis in the spleen occurred at the lowest concentration administered. Hematology evaluation showed progressive anemia associated with a cellular depletion of bone marrow and fibrosis of the splenic capsule. LOAEL (male) = 4000 ppm (approximately 529 mg/kg-bw/day; based on testicular degeneration and increased hematopoiesis in the spleen ) NOAEL (male) = 2000 ppm (approximately 300 mg/kg-bw/day) LOAEL (female) = 2000 ppm (approximately 492 mg/kg-bw/day; based on adrenal gland hypertrophy and increased hematopoiesis in the spleen at the lowest dose tested ) NOAEL (female) = Not established

Reproductive Toxicity

There were no specific reproductive toxicity tests repo rted by the submitter for monoglyme. However, positive effects (testicular degeneration) in the repeated-dose toxic ity studies using the surrogate chemical 2-methoxyethanol along with the submitted developmental toxicity study (n ext section) were used to address the reproductive endpoints for the purposes of the HPV Challenge Prog ram. Therefore, NOAEL/L OAELs for fertility and/or reproductive toxicity cannot be determined for these studies.

Developmental Toxicity

Monoglyme (CAS No. 110-71-4) (1) Pregnant female Harlan Sprague-Dawley rats (6-28 per group) were administered monoglyme via oral gavage at doses of 0, 30, 60, 120, 250, 500 or 1000 mg/kg-bw/day on days 8 through 18 of gestation. On gestation day 19, dams were sacrificed for teratological evaluation of pups. Fetuses were assessed for litter size, early deaths, gross malformations, perinatal size, fetal body weight and skeletal examination. Dose levels of 120, 250, 500 and 1000 mg/kg-bw/day produced 100% resorptions. At the three highest doses, the necrotic masses were uniformly small; suggesting early embryonic death soon after treatment was initiated. At 120 mg/kg-bw/day, fetuses were larger, having survived for somewhat longer times. These observ ations are consistent with the dose-dependent reduction by the test substance in maternal weight gain. Animals at 60 mg/kg-bw/day showed a 7-fold increase in resorptions per litter. Fetal mortality was not elevated at 30 mg/kg-bw /day. In the 60 mg/kg-bw/day group, fewer than 1 pup per litter survived compared to 12.3 in controls. These pups did not recei ve maternal care and none survived beyond postnatal day 1. At 120 mg/kg-bw and above, there was complete early fetal death and possible maternal toxicity. The lower doses were associated with fetotoxicity includ ing stillbirths and reduced body weight. No major external malformations were reported. There was a delay in parturition at the 60 mg/kg-bw dose and some delay was seen atU.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 14 30 mg/kg-bw/day. Substantial edema of fetuses was seen at 60 mg/kg-bw/day. Edema was less frequent at 30 mg/kg-bw/day but may have been biologically significant since edema was not seen in control fetuses. Fetuses exposed to 60 mg/kg-bw/day showed a reduced stain rating in the skeletal assay (not re stricted to specific bones), indicating less advanced bone ossification and consistent with overall retardation of growth and development. A NOEL for developmental effects was not established. LOAEL (maternal toxicity) = 120 mg/kg-bw/day; based on decreased maternal body weight gain, partly due to early deaths ) NOAEL (maternal toxicity) = 60 mg/kg-bw/day LOAEL (developmental toxicity) = 30 mg/kg-bw/day; based on increased stillborn, fetal edema, increased gestation length ) NOAEL (developmental toxi city) = Not established

(2) Pregnant female CRJ:CD-1 mice were administered via oral gavage 0, 250, 350 or 490 mg/kg-bw/day monoglyme on days 7 through 10 of gestation. At the end of the dosing period, the dams were sacrificed for evaluation of pups. Fetuses were assessed for litter size, ea rly deaths, gross malformations, perinatal size, fetal body weight and skeletal examinat ion. There was a clear dose-dependent increase in malformations (exencephaly) and embryo toxicity (mortality). Maternal data were scant a nd information on relevant parameters for gauging maternal toxicity was not provided. Administration of monoglyme was associated with increases in external and skeletal malformations (rib fusions and malformation of vertebrae). The 250 mg/kg-bw/day dose appears to be a NOAEL

for external malformations but consider able skeletal defects and reduced feta l body weight suggest that the NOAEL

was not established. LOAEL (maternal toxicity) > 490 mg/kg-bw/day; based on no treatment-related effects at highest dose tested ) NOAEL (maternal toxicity) = 490 mg/kg-bw/day LOAEL (developmental toxicity) = 250 mg/kg-bw/day ; based on decreased fetal body weight and skeletal

defects ) NOAEL (developmental toxi city) = Not established

(3) Fifty female CD-1 mice were administered monoglyme via oral gavage at 0 or 2000 mg/kg-bw/day on days 7 through 14 of gestation in a screening test conducted by the National Toxicology Program (NTP). If no pups were delivered by day 23 of gestation, mice were sacrificed. During day 8 and 18 of gestation, the body weight of

controls increased 13.3% whereas treated animals showed a weight loss of 7%. No viable litters were produced from 49 pregnant mice dosed at 2000 mg/kg-bw/day. As the uteri of most of these were sodium sulfide positive, it was concluded that 1,2-dimehoxyethane causes embryotoxicity at 2000 mg/kg-bw/day. LOAEL < 2000mg/kg-bw/day (based on no viable litters)

NOAEL = Not established

Genetic Toxicity – Gene Mutation

In vitro Monoglyme (CAS No. 110-71-4) (1) A Chinese hamster ovary cell mutation test (HGPRT) with monoglyme was conducted at 4.0, 4.5, 5.0, 5.5 and

6.0% v/v with and without metabolic activation. Po sitive and negative controls were used and responded appropriately. Cytotoxicity increased with increasing concentrations of monoglyme. No genotoxic activity was

detected either with or without metabolic activation. Monoglyme was not mut agenic in this assay.

Monoglyme (CAS No. 110-71-4) (2) In an in vitro bacterial reverse mutation assay using S. typhimurium strains TA 98 and TA 100, monoglyme tested positive in both strains without mammalian metabolic activation and negative in both strains with metabolic activation. Concentrations tested were from 333 to 10,000 (assumed to be ug/plate). These data were not presented in the HPV Submission but may be found at the following URL from the National Toxicology Program (NTP):http://ntpapps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=sa lmonella.salmonellaData&study_no=206306&cas_no=110%2D 71%2D4&endpointlist=SA

. Monoglyme induced gene mutations in bacteria in the absence of meta bolic activation in this assayU.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 15 Genetic Toxicity – Chromosomal Aberrations

In vitro In sister chromatid exchange test (SCE) using Chinese hamster ovary cells, monoglyme was tested at 2.0, 3.0 and

4.0% v/v with and without metabolic activation. Po sitive and negative controls were used and responded appropriately. Cytotoxicity was observed with increasing concentration. Monoglyme produced SCE in the absence and presence of metabolic activation. A high number of cells were also observed with significant types of chromosomal aberrations suggesting that the material was a cl astogenic, especially in the presence of S9 activation. Monoglyme induced sister chromatid ex change in the presence and absence of metabolic activation in this

assay.

Genetic Toxicity – Other

In vitro Monoglyme (CAS No. 110-71-4) Rat hepatocytes were exposed to 0, 0. 03, 0.1, 0.3, 1.0, 3.0 and 6.0% v/v of monoglyme. Negative and positive controls were used. Monoglyme did not produce either statistically significant or dose-related increases in the amount of unscheduled DNA synthesis activity. There was no evidence of genotoxic activity. Monoglyme was not mut agenic in this assay.

Conclusion: The acute toxicity of monoglyme is low via oral, dermal and inhalation routes of exposure. Repeated-dose studies with monoglyme have not been conducted. However, detailed information on the metabolic pathway of monoglyme justifies the use of 2-methoxyethanol, a major metabolite of this chemical, as a supporti ng chemical for assessing the repeated-dose toxicity of monoglyme. In 13-week drinking water studies of 2-methoxyethanol, testicular degeneration and adverse effects on hematopoiesis were seen in both rats and mice. Additional target organs in these studies were the thymus in rats and adrenal gland in mice. Adverse effects to reproduction are based on metabolism of monoglyme to 2-methoxy acetic acid, which interferes with sperm production. In a screening test performed by the National Toxicology Program (NTP), no viable pups were delivered from mice given single oral doses of monoglyme during days 7 through 14 of gestation. Body weight loss was seen in treated dams. The following effects were observed in oral developmental toxicity st udies: increased stillborn, fetal edema, and increased gestation length in rats and decreased fetal body weight and skeletal defects in mice. Increases in gene

mutations were observed in bacterial cells without meta bolic activation, but not when metabolic activation was present. In mammalian cells, monoglyme did not show potential to induce gene mutations, but did induce sister chromatid exchanges (SCE) and chromosomal aberrations.

The potential health hazard of monoglyme is high based on the results of the available repeated-dose and developmental toxicity studies.

4. Hazard Characterization

Monoglyme is a liquid at room temperature. It has high wate r solubility and high vapor pressure. It is highly mobile in soil, does not bioaccumulate, and does not hydrolyze under environmental pHs. Biodegradation is expected to be slow. In the atmosphere, it is expected to photodegrade within slightly over one day. Based on these findings, monoglyme is expected to be moderately persistent (P2) and the bioaccumulation potential for monoglyme is ranked low (B1) based on its estimated bioconcentration factor (BCF) of 3.

The evaluation of available aquatic toxicity data on supporting chemicals (primarily 1,3-dioxalane) for fish, aquatic invertebrates and aquatic plants indicates that the potential acute hazard of monoglyme to aquatic organisms is low.

The acute toxicity of monoglyme is low via oral, dermal and inhalation routes of exposure. Repeated-dose studies with monoglyme have not been conducted. However, detailed information on the metabolic pathway of monoglyme justifies the use of 2-methoxyethanol, a major metabolite of this chemical, as a supporti ng chemical for assessing the repeated-dose toxicity of monoglyme. In 13-week drinking water studies of 2-methoxyethanol, testicular degeneration and adverse effects on hematopoiesis were seen in both rats and mice. Additional target organs inU.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 16 these studies were the thymus in rats and adrenal gland in mice. Adverse effects to reproduction are based on metabolism of monoglyme to 2-methoxy acetic acid, which interferes with sperm production. In a screening test performed by the National Toxicology Program (NTP), no viable pups were delivered from mice given single oral doses of monoglyme during days 7 through 14 of gestation. Body weight loss was seen in treated dams. The following effects were observed in oral developmental toxicity studi es: increased numbers of stillborn pups, fetal edema, and increased gestation length in rats and decreas ed fetal body weight and skeletal defects in mice. Increases in gene mutations were observed in bacterial ce lls without metabolic activation, but not when metabolic activation was present. In mammalian cells, monoglyme did not show potential to induce gene mutations, but did induce sister chromatid exchanges (S CE) and chromosomal aberrations.

The potential health hazard of monoglyme is high based on the results of the repeated-dose (blood, thymus, adrenal gland, and testicular degeneration) and developmental (increased fetal death and skeletal effects and decreased fetal body weight) toxicity studies. Available data indicate monoglyme has the potential to be genotoxic.

5. Data Gaps

No data gaps were identified under the HPV Challenge Program.U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 17 APPENDIX

Summary Table of the Screening Information Data Set

as submitted under the U.S. HPV Challenge Program

Endpoints SPONSORED CHEMICAL Monoglyme

(110-71-4) SUPPORTING

CHEMICAL 1,3-Dioxolane

(CAS No. 646-06-0) SUPPORTING

CHEMICAL 2-Methoxyethanol (CAS No. 109-86-4)

Structure O

O O

O OH O

Summary of Environmental Effects – Aquatic Toxicity Data

Fish

96-h LC 50 (mg/L) No Measured Data

7984 (est) > 95.4

8148 (est.) -

Aquatic Invertebrates

48-h EC 50 (mg/L) No Measured Data

7344 (est.) > 772 mg/L

7443 (est) -

Aquatic Plants

72-h EC 50 (mg/L)

(growth)

(biomass) 4043 mg/L (est) (96-h) 4074 (est.)

> 877 mg/L

> 877 mg/L -

Summary of Human Health Data

Acute Oral Toxicity

LD 50 (mg/kg-bw) > 4000 (female rat) - -

Acute Dermal Toxicity

LD 50 (mg/kg-bw) > 1000 (female rat) - 

### -

Acute Inhalation Toxicity

LC 50 (mg/L) 20 - 63 (6-h) - 

### -

Repeated-Dose Toxicity

NOAEL/LOAEL No Data - RatU.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 18 Summary Table of the Screening Information Data Set

as submitted under the U.S. HPV Challenge Program

Endpoints SPONSORED CHEMICAL Monoglyme

(110-71-4) SUPPORTING

CHEMICAL 1,3-Dioxolane

(CAS No. 646-06-0) SUPPORTING

CHEMICAL 2-Methoxyethanol (CAS No. 109-86-4)

(mg/kg-bw/day) (RA)

Rat

(drinking water)

(No NOAEL)

LOAEL = 70

Mouse

(drinking water)

NOAEL = 300 (male) and none (female)

LOAEL = 529 (male) and 492 (female) (drinking water)

(No NOAEL)

LOAEL = 70

Mouse

(drinking water)

NOAEL = 300 (male) and none (female)

LOAEL = 529 (male) and 492 (female)

Reproductive Toxicity

NOAEL/LOAEL

(mg/kg-bw/day) Addressed by positive findings in both repeated dose [testicular effects in 2- methoxyethanol study] and developmental [fetal death and effects] studies -



### -

Developmental Toxicity

NOAEL/LOAEL

(mg/kg-bw/day)

(maternal toxicity)

Rat 

### -U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 19 Summary Table of the Screening Information Data Set

as submitted under the U.S. HPV Challenge Program

Endpoints SPONSORED CHEMICAL Monoglyme

(110-71-4) SUPPORTING

CHEMICAL 1,3-Dioxolane

(CAS No. 646-06-0) SUPPORTING

CHEMICAL 2-Methoxyethanol (CAS No. 109-86-4)

(developmental toxicity)

(maternal toxicity)

(developmental toxicity) LOAEL = 120

NAOEL = 60

LOAEL = 30

NOAEL =Not established

Mouse

NOAEL/LOAEL = 490

LOAEL = 250

NOAEL = Not established 

### -

Genetic Toxicity –

Gene Mutation

In vitro Positive (bacteria – without activation)

Negative (bacteria – with activation) - 

### -

Genetic Toxicity –

Gene Mutation

In vivo ─ - 

### -

Genetic Toxicity – Chromosomal

Aberrations

In vitro Positive - 

### -

Genetic Toxicity – Chromosomal

Aberrations

In vivo ⎯ - 

### -

Genetic Toxicity – Other

In vitro Negative (UDS study)

- 

### -U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 20 Summary Table of the Screening Information Data Set

as submitted under the U.S. HPV Challenge Program

Endpoints SPONSORED CHEMICAL Monoglyme

(110-71-4) SUPPORTING

CHEMICAL 1,3-Dioxolane

(CAS No. 646-06-0) SUPPORTING

CHEMICAL 2-Methoxyethanol (CAS No. 109-86-4)

Additional Information

⎯ - 

### -

− indicates that the endpoint was not addressed for this chemical. Bold values represent measured data.

RA = Read Across

REFERENCES

EFDB, 2007. Environmental Fate Data Base. Accessed 2 Ja nuary 2008 for several ether analogs (CAS nos. 628-81- 9; 628-28-4; 60-29-7; 115-10-6; 540-67-0; 108-20-3; 6863-58-7; 142-96-1). http://www.syrres.com/esc/biodeg.htm

Ferro, 2001. Robust Summaries & Test Plans: monoglyme HPV Test Pl an, submitted by Fe rro Corporation http://www.epa.gov/chemrtk/pubs/s ummaries/dimetho/c13455tp.pdf

FR 1999, Category for Persistent, Bioaccumul ative, and Toxic New Chemical Substances. Federal Register 64, Number 213 (November 4, 1999) Page 60194-60204

HSDB, 2007. Hazard Substances Data Base. As cited in HSDB record for monoglym e, accessed August 28, 2007. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB

.

USEPA, 2007. EPI Suite TM (version 3.2) PC-Computer software developed by EPA’s Office of Pollution Prevention Toxics and Syracuse Re search Corporation. http://www.epa.gov/opptintr/exposure/pubs/episuite.htmU.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 21 

# Screening Level Exposure Characterization for HPV Challenge Chemical

1,2 Dimethoxyethane

(Monoglyme)

CAS #110-71-4

March 14, 2008

Prepared by

Exposure Asses s ment Branch Chemical Engineering Branch Economics Exposure and Technology Division

Office of Pollution Prevention and Toxics Environmental Protection Agency

1200 Pennsylvania Avenue, NW

Washington, DC 20460-0001U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 22 

# Screening Level Exposure Characterization for HPV Challenge Chemical

1,2 Dimethoxyethane (CAS #110-71-4)

Non-CBI Executive Summary

This chemical has some public use and exposure information in the HPV Challenge Program

submission. The information indicates that the 1,2-dimethoxyethane is used primarily as an industrial solvent, process aid, and as a compone nt of lithium batteries and industrial coatings (Ferro, 2001).

1,2 Dimethoxyethane was manufactured and/or impor ted in the United States in calendar year 2005 (USEPA, 2007a). This chemical has an ag gregated volume produced and/or imported in the range of 1,000,000 to 10,000,000 pounds. Persons submitting Inventory Update Reporting (IUR) information in 2006 asserted that some of the information was confidential business information (CBI) and therefore cannot be disclo sed. Data and information that are CBI have been excluded from this summary.

Exposure was characterized using both public, no n-confidential sources and one or more IUR submissions were available at the time the expos ure characterization was written. If additional information warrants an update of the exposure ch aracterization, the update will be posted on the

EPA website.

A SIDS dossier has not been prepared for this chemical. The chemical is not on the Toxics Release Inventory (USEPA, 2007b).

Exposure to Workers

This chemical has a vapor pressure of 48 torr at 20°C (USEPA, 2007c). OPPT has established 0.001 torr as a value above which worker exposures to vapors should be estimated for chemical assessments. Therefore, this chemical’s vapo r pressure could result in significant worker exposure if workers are near to the chemical. This chemical does not ha ve an OSHA Permissible Exposure Limit (NIOSH, 2007a).

The National Occupational Exposure Survey (NOES), conducted between 1981 and 1983 estimated a total of 3319 workers potentially expo sed to this chemical (NIOSH, 2007b). Based on IUR reporting, the maximum total number of work ers likely to be exposed to this chemical during manufacturing and industr ial processing and use is less than 100. There may be additional potentially exposed workers that ar e not included in this estimate since not all production volume has been accounted for, and ther e is at least one use that contains a "Not Readily Obtainable" (NRO) response among the submissions. The IUR based ranking for worker exposure is high.

Differences between numbers of workers estimated by IUR submitters and by the NOES are attributable to many factors, including time, sc ope, and method of the estimates. For example,U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 23 NOES estimates are for all workplaces while IUR are for industrial workplaces only, and NOES used a survey and extrapolation method while IUR submitters simply provide their best estimates

based on available information for the specific reporting year.

Exposures to General Population and the Environment

The chemical is not on the Toxics Release Inventory (USEPA, 2007a). The potential for exposure to the general population and the environment is likely, based on the totality of the information considered and expert judgment. EP A assumes, for the purposes of this risk based prioritization, that the potentia l for exposure to the general p opulation and the environment is high.

Limited data suggest that 1,2-dimethoxyethane is resistant to biodegrada tion; therefore it is expected to be moderately persistent (P 2). 1,2-dimethoxyethane is ranked (B1) for

bioaccumulation because its’ estima ted BCF is 3 (USEPA, 2007c).

Exposure to Commercial Workers and Consumers

Non-CBI IUR information indicates there is potential exposure to 1,2-dimethoxyethane for

commercial workers and consumers. This chem ical has a vapor pressu re of 48 torr at 20°C (USEPA, 2007c). The vapor pressure could result in significant worker exposures to vapors if commercial workers or consumers are near to pr oducts containing the chemical. Information provided suggests that 1,2-dimet hoxyethane will be used in consumer products. The IUR ranking

for commercial workers and cons umers is high due to the likeli hood that there will be exposure

to this chemical based on IUR data.

Exposure to Children

Information provided suggests that 1,2-dimethoxye thane will be used in commercial/consumer products, including children’s pr oducts. The IUR ranking for ch ildren is high due to the likelihood that there will be exposure to this chemical based on IUR data.U.S. Environmental Protection Agency 3/18/ 2008 Supporting Documents for Risk-Based Prioritization



### 24 References

Ferro, 2001. 1,2-Dimethoxyethane U.S. EPA HPV Challenge Program Submission. December 2001. Ferro Corporation. http://www.epa.gov/chemrtk/pubs/summaries/dimetho/c13455tp.pdf

HSDB, 2007. Hazardous Substances Data Bank. Accessed December 2007. 1,2

DIMETHOXYETHANE http://toxnet.nlm.nih.gov/cgi-bin/ sis/search/f?.temp/~6xho9e:1

NIOSH, 2007a. OSHA PEL Project Documentation. Accessed August, 2007. http://www.cdc.gov/niosh/pel88/npelcas.html

NIOSH, 2007b. National Occupational Exposur e Survey (NOES). Accessed December 2007. http://www.cdc.gov/noes/noes2/83728occ.html

USEPA, 2007a. EPA database of 2006 Inventory Update Rule Reporting (contains Confidential Business Information). Accessed September 2007.

USEPA, 2007b. Toxic Release In ventory. United States Envi ronmental Protection Agency, Accessed August, 2007. http://www.epa.gov/tri/

USEPA, 2007c. Physical/Chemical and Enviro nmental Fate Characterization for High

Production Volume Chemicals Chem ical Name: 1,2 Dimethoxyethane