Screening-Level Hazard Characterization Sponsored Chemical 1,2-Dimethoxyethane (CAS No. 110-71-4) [9th CI Name: Ethane, 1,2-dimethoxy-] Supporting Chemical 1,3-Dioxolane (CAS No. 646-06-0) 2-Methoxyethanol (CAS No. 109-86-4)

SCREENING-LEVEL HAZARD CHARACTERIZATION
FOR HIGH PRODUCTION VOLUME CHEMICALS

SPONSORED CHEMICAL

1,2-Dimethoxyethane (CAS No. 110-71-4)
[9th 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

Prepared by

High Production Volume Chemicals Branch
Risk Assessment Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001

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SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS

The High Production Volume (HPV) Challenge Program1 is a voluntary initiative aimed at developing and making
publicly available screening-level health and environmental effects information on chemicals 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 Set1'2) endpoints that
are screening-level indicators 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 hazard-
based 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 website3.

Tier 1 is a computerized sorting process 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 guidance2'4 and is based primarily on hazard data provided by sponsors.
EPA may also include additional or updated hazard information of which EPA, sponsors or other parties have
become aware. The hazard characterization may also identify data gaps that will become the basis for a subsequent
data needs assessment where deemed necessary. Under the HPV Challenge Program, chemicals that have similar
chemical structures, properties 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 endpoints for all
category members. As part of Tier 2, evaluation of chemical category rationale and composition and data
extrapolation(s) among category members is performed in accord with established EPA2 and OECD5 guidance.

The screening-level hazard characterizations that emerge from Tier 2 are important contributors to OPPT's existing
chemicals review process. These hazard characterizations are technical documents intended to support 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 assessment 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 the hazard characterization documents.

The screening-level hazard characterizations, as the name indicates, do not evaluate the potential 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 chemicals in the HPV Challenge Program, 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 characterizations4'6. The screening-level
risk characterizations will inform EPA on the need for further 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-
based decision-making process on HPV chemicals which applies the results of the successful U.S. High Production
Volume Challenge Program and the IUR to support judgments concerning the need, if any, for further action.

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. HPV Chemicals Hazard Characterization website (http://www.epa.gov/hpvis/abouthc.html).

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

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

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

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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; 9th CI name: ethane, 1,2-dimethoxy-) 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/cl3455tc.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 characterization is based primarily on the review of the test plan and robust summaries
of studies submitted by the sponsor(s) under the HPV Challenge 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. A summary table of SIDS endpoint data with the
structure(s) of the sponsored chemical(s) is included in the appendix. 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 level definitions and hazard assessment practices.

Supporting Chemical Justification

The sponsor submitted data for additional chemicals to support 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 1,2-dimethoxy ethane. Chemical structures are provided in the data table
in the Appendix.

Sum man-Conclusion

The log k \;iliic i»f 1,2-tlimclIk»n\clIkiiic indicates ilial lis potential lo bioncciiniiilalc is expected lo be low
l.2-l)iniclho\\clhniic is not readiK biodegradable indicating il lias die potential lo persist mi die en\ iroiiniciit

I lie e\ nhialioii of a\ ailahle aquatic to\icit> dala on supporting chemicals lor fish, aquatic iii\ eriehmies and aquatic
plains indieales ilial llie poienlial aeule lia/ard of 1.2-diinellio\\elhaiie lo ai|iialie organisms is low

I lie aeule to\icit> of 1.2-diinellio\\elhaiie is low \ la oral, dermal and inhalation routes of e\posiire Repeated-dose
studies w itli 1.2-dinielho\\ethane ha\e not been conducted I lowe\er. detailed information on the metahohe
pathwas of 1.2-dinielho\\ ethane justifies the use of 2-nielho\\ ethanol. a major metabolite of this chemical, as a
supporting chemical lor assessing the repeated-dose lo\icil> of 1.2-dinielho\\ ethane In I '-week drinking water
studies of 2-nielho\\ ethanol. testicular degeneration and ad\ eise effects on henialopoicsis were seen in hotli rats and
mice \ddilional target organs in these studies were the th\ inns mi rats and adrenal gland in mice \d\erse effects
lo reproduction are hased on metabolism of 1.2-dinielho\\ethane lo 2-nielho\\ acetic acid, w Inch interferes w nil
sperm production. In a icprodiicli\ e ti»\icit\-screening test, no \ lahle pnps were dch\cred from mice gi\en oral
doses of 1.2-diniclho\\clhaiic during da\s ~ through 14 of gestation l!od\ weight losswasseen in treated dams In
oral de\elopnieiital lo\icil> studies, doses helow those that were ninleriinlK Ionic produced increased stillborn, fetal
edema, and increased gestation length in rats and decreased fetal bod> weight and skeletal delects in mice. In
mammalian cells. 1.2-dinielho\\ethane did not show potential lo induce gene miitatioiis. bin did induce sister
chromatid exchanges (SCI j and chromosomal aberrations

I lie potential health lia/ard of 1.2-dinielhowelhaiie is high based on the results of the repeated-dose and
reproduce e de\ elopnieiital lo\icil>

\o dala gaps were identified under the I ll'V Challenge I'logram

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1. Physical-Chemical Properties and Environmental Fate

A summary of physical-chemical properties and environmental fate data submitted is provided in the Appendix. For
the purpose of the screening-level hazard characterization, the review and summary of these data was limited to the
octanol-water partition coefficient and biodegradation endpoints as indictors of bioaccumulation and persistence,
respectively.

Octanol-Water Partition Coefficient
1,2-Dimethoxyethane (CASNo. 110-71-4)

LogKow: -0.21(measured)

Biodegradation

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

In ready biodegradation test, the inoculum was prepared from a petroleum refinery waste treatment. After 33 weeks
no biodegradation was seen for the test substance.

1,2-dimethoxyethane is not readily biodegradable.

Conclusion: The log Kow value of 1,2-dimethoxyethane indicates that its potential to bioaccumulate is expected to
be low. 1,2-Dimethoxy ethane is not readily biodegradable indicating it has the potential to persist in the
environment.

2. Environmental Effects - Aquatic Toxicity
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 LCS0 > 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 mortality 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 ECS0 > 764 mg/L

48-h EC50 > 772 mg/L (highest concentration tested)

(2)	Daphnia magna were exposed to supporting chemical 2-methoxyethanol for 24 hours in a static test (no other
details were provided).

24-h ECS0 > 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

4

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inhibition compared to the control was 19% at 877 mg/L. There was no significant statistical difference between the

algal growth of the control and test solutions.

72-h EC50 (biomass) > 877 mg/L (highest measured concentration)

72-h EC50 (growth) > 877 mg/L

(2) A standard toxicity test for aquatic plants was not provided for 1,2-dimethoxyethane. A 96-hour EC50 for green
algae, estimated by ECOSAR, was provided to evaluate the plant toxicity of 1,2-dimethoxyethane.

96-h EC50 = 4043 (estimated)

Conclusion: The evaluation of available aquatic toxicity data on supporting chemicals for fish, aquatic
invertebrates and aquatic plants indicates that the potential hazard of 1,2-dimethoxyethane to aquatic organisms is
low.

3. Human Health Effects
Acute Oral Toxicity

1,2-Dimethoxyethane (CASNo. 110-71-4)

Female rats (4/group) were administered 1,2-dimethoxyethane 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.

LDS0 > 4000 mg/kg-bw

Acute Inhalation Toxicity
1,2-Dimethoxy ethane (CAS No. 110-71-4)

Rats (sex and number/group not specified) were administered 1,2-dimethoxyethane 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 < LC50 < 63 mg/L

Acute Dermal Toxicity
1,2-Dimethoxy ethane (CAS No. 110-71-4)

Female rabbits (2/group) were administered dermal doses of 1,2-dimethoxyethane 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.

LDS0 = 1000 - 2000 mg/kg-bw

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Repeated-Dose Toxicity

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 and
hematopoietic tissues (spleen, bone marrow and liver). Higher doses produced a progressive anemia. A dose-
related degeneration of the germinal epithelium in the seminiferous 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 adrenal gland in female mice. A NOAEL was not achieved for
females since adrenal gland hypertrophy and increased hematopoiesis 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

1,2-Dimethoxyethane (CASNo. 110-71-4)

Fifty female CD-I mice were administered 1,2-dimethoxyethane via oral gavage at 0 or 2000 mg/kg-bw/day on days
7 through 14 of gestation. 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

Developmental Toxicity

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

(1) Pregnant female Harlan Sprague-Dawley rats (6-28 per group) were administered 1,2-dimethoxy ethane 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 observations 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

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than 1 pup per litter survived compared to 12.3 in controls. These pups did not receive 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 including 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 at 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 restricted 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 toxicity) = Not established

(2) Pregnant female CRJ:CD-1 mice were administered via oral gavage 0, 250, 350 or 490 mg/kg-bw/day
1,2-dimethoxyethane 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, early deaths, gross malformations, perinatal size, fetal
body weight and skeletal examination. There was a clear dose-dependent increase in malformations (exencephaly)
and embryo toxicity (mortality). Maternal data were scant and information on relevant parameters for gauging
maternal toxicity was not provided. Administration of 1,2-dimethoxy ethane 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 considerable skeletal defects and reduced fetal 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 toxicity) = Not established

Genetic Toxicity - Gene Mutation
In vitro

1,2-Dimethoxyethane (CASNo. 110-71-4)

A Chinese hamster ovary cell mutation test (HGPRT) with 1,2-dimethoxyethane was conducted at 4.0, 4.5, 5.0, 5.5
and 6.0% v/v with and without metabolic activation. Positive and negative controls were used and responded
appropriately. Cytotoxicity increased with increasing concentrations of 1,2-dimethoxyethane. No genotoxic activity
was detected either with or without metabolic activation.

1,2-Dimethoxy ethane was not mutagenic in this assay.

Genetic Toxicity - Chromosomal Aberrations

In vitro

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

In sister chromatid exchange test (SCE) using Chinese hamster ovary cells, 1,2-dimethoxyethane was tested at 2.0,
3.0 and 4.0% v/v with and without metabolic activation. Positive and negative controls were used and responded
appropriately. Cytotoxicity was observed with increasing concentration. 1,2-Dimethoxyethane 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 clastogenic, especially in the presence of S9
activation.

1,2-Dimethoxyethane induced sister chromatid exchange in the presence and absence of metabolic activation
in this assay.

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Genetic Toxicity - Other
In vitro

1,2-Dimethoxyethane (CASNo. 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 1,2-dimethoxyethane. Negative and
positive controls were used. 1,2-Dimethoxy ethane 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.
1,2-Dimethoxy ethane was not mutagenic in this assay.

Conclusion: The acute toxicity of 1,2-dimethoxyethane is low via oral, dermal and inhalation routes of exposure.
Repeated-dose studies with 1,2-dimethoxyethane have not been conducted. However, detailed information on the
metabolic pathway of 1,2-dimethoxyethane justifies the use of 2-methoxyethanol, a major metabolite of this
chemical, as a supporting chemical for assessing the repeated-dose toxicity of 1,2-dimethoxyethane. 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 1,2-dimethoxyethane to 2-methoxy acetic acid, which
interferes with sperm production. In a reproductive toxicity-screening test, no viable pups were delivered from mice
given oral doses of 1,2-dimethoxyethane during days 7 through 14 of gestation. Body weight loss was seen in
treated dams. In oral developmental toxicity studies, doses below those that were maternally toxic produced
increased stillborn, fetal edema, and increased gestation length in rats and decreased fetal body weight and skeletal
defects in mice. In mammalian cells, 1,2-dimethoxyethane did not show potential to induce gene mutations, but did
induce sister chromatid exchanges (SCE) and chromosomal aberrations.

The potential health hazard of 1,2-dimethoxyethane is high based on the results of the repeated-dose and
reproductive/developmental toxicity.

4. Hazard Characterization

The log Kow value of 1,2-dimethoxyethane indicates that its potential to bioaccumulate is expected to be low.
1,2-Dimethoxyethane is not readily biodegradable indicating it has the potential to persist in the environment.

The evaluation of available aquatic toxicity data on supporting chemicals for fish, aquatic invertebrates and aquatic
plants indicates that the potential acute hazard of 1,2-dimethoxyethane to aquatic organisms is low.

The acute toxicity of 1,2-dimethoxyethane is low via oral, dermal and inhalation routes of exposure. Repeated-dose
studies with 1,2-dimethoxyethane have not been conducted. However, detailed information on the metabolic
pathway of 1,2-dimethoxyethane justifies the use of 2-methoxyethanol, a major metabolite of this chemical, as a
supporting chemical for assessing the repeated-dose toxicity of 1,2-dimethoxyethane. 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 1,2-dimethoxyethane to 2-methoxy acetic acid, which interferes with
sperm production. In a reproductive toxicity-screening test, no viable pups were delivered from mice given oral
doses of 1,2-dimethoxyethane during days 7 through 14 of gestation. Body weight loss was seen in treated dams. In
oral developmental toxicity studies, doses below those that were maternally toxic produced increased stillborn, fetal
edema, and increased gestation length in rats and decreased fetal body weight and skeletal defects in mice. In
mammalian cells, 1,2-dimethoxyethane did not show potential to induce gene mutations, but did induce sister
chromatid exchanges (SCE) and chromosomal aberrations.

The potential health hazard of 1,2-dimethoxyethane is high based on the results of the repeated-dose and
reproductive/developmental toxicity.

5. Data Gaps

No data gaps were identified under the HPV Challenge Program.

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APPENDIX

Summary Table (if the Screening Information Data Set
as submitted under the U.S. HPV Challenge Program

Endpoints

SPONSORED CHEMICAL

1,2-Dimethoxvethane
(110-71-4)

SUPPORTING
CHEMICAL
1,3-Dioxolanc
(CAS No. 646-06-0)

SUPPORTING
CHEMICAL
2-Methoxvethanol (CAS
No. 1(19-86-4)

Structure





"*OH

Summary of Physical-Chemical Properties and Environmental Fate Data

Melting Point (°C)

-58

—

—

Boiling Point (°C)

82-83, 85

—

—

Vapor Pressure
(hPa at 25°C)

64 hPa at 20 °C

—

—

Log K„w

-0.21

—

—

Water Solubility
(mg/L at 25°C)

Soluble in water in all
proportions

—

—

Direct Photodegradation

—

—

—

Indirect (OH ) Photodegradation
Half-life (t1/2)

8.2 h

—

—

Stability in Water (Hydrolysis) (ti/2)

Not susceptible to hydrolysis
at pH 4 to 9

—

—

Fugacity
(Level III Model)

Air(%)
Water (%)
Soil (%)
Sediment(%)

<1
61
38
<1





Biodegradation at 28 days (%)

No biodegradation after 33
weeks

Not readily biodegradable





Summary of Environmental Effects - Aquatic Toxicity Data

Fish

96-h LCS0 (mg/L)

No Data

> 95.4 mg/L

—

Aquatic Invertebrates
48-h ECS0 (mg/L)

No Data

> 772 mg/L

—

Aquatic Plants
72-h EC50 (mg/L)
(growth)
(biomass)

4043 mg/L (e) (96-h)

>	877 mg/L

>	877 mg/L

—

Summary of Human Health Data

Acute Oral Toxicity
LDS0 (mg/kg-bw)

> 4000 (female rat)

	

	

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Summary Table (if the Screening Information Data Set
as submitted under the U.S. HPV Challenge Program

Endpoints

SPONSORED CHEMICAL

1,2-Dimethoxvethane
(110-71-4)

SUPPORTING
CHEMICAL
1,3-Dioxolanc
(CAS No. 646-06-0)

SUPPORTING
CHEMICAL
2-Methoxvethanol (CAS
No. 109-86-4)

Acute Dermal Toxicity
LDS0 (mg/kg-bw)

> 1000 (female rat)

—

—

Acute Inhalation Toxicity
LCS0 (mg/L)

20-63 (6-h)

—

—

Repeated-Dose Toxicity

NOAEL/LOAEL

(mg/kg-bw/day)

No Data



Rat

(drinking water)
750 ppm (70)

Mouse
(drinking water)
4000 ppm (529, male)
2000 ppm (492, female)

Reproductive Toxicity

NOAEL/LOAEL

(mg/kg-bw/day)

NOAEL = Not established
LOAEL < 2000



	

Developmental Toxicity

NOAEL/LOAEL

(mg/kg-bw/day)

(maternal toxicity)

Rat

LOAEL = 120
NAOEL = 60





(developmental toxicity)

LOAEL = 30
NAOEL =Not established





(maternal toxicity)

Mouse
NOAEL/LOAEL = 490





(developmental toxicity)

LOAEL = 250
NOAEL = Not established





Genetic Toxicity -
Gene Mutation
In vitro

Negative

—

	

Genetic Toxicity -
Gene Mutation
In vivo





	

Genetic Toxicity - Chromosomal

Aberrations

In vitro

Positive

—

	

Genetic Toxicity - Chromosomal

Aberrations

In vivo

	



	

Additional Information

—

—

	

- indicates that the endpoint was not addressed for this chemical.

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