[Federal Register Volume 80, Number 195 (Thursday, October 8, 2015)]
[Proposed Rules]
[Pages 60818-60825]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-25674]
[[Page 60818]]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 372
[EPA-HQ-TRI-2015-0352; FRL 9935-38-OEI]
Ethylene Glycol Monobutyl Ether; Community Right-To-Know Toxic
Chemical Release Reporting
AGENCY: Environmental Protection Agency (EPA).
ACTION: Denial of petition.
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SUMMARY: Environmental Protection Agency (EPA) is denying a petition to
remove ethylene glycol monobutyl ether (EGBE) from the category Certain
Glycol Ethers under the list of chemicals subject to reporting under
section 313 of the Emergency Planning and Community Right-to-Know Act
(EPCRA) of 1986 and section 6607 of the Pollution Prevention Act (PPA)
of 1990. EPA has reviewed the available data on this chemical and has
determined that EGBE does not meet the deletion criterion of EPCRA
section 313(d)(3). Specifically, EPA is denying this petition because
EPA's review of the petition and available information resulted in the
conclusion that EGBE meets the listing criterion of EPCRA section
313(d)(2)(B) due to its potential to cause serious or irreversible
chronic health effects in humans, specifically, liver toxicity and
concerns for hematological effects.
DATES: EPA denied this petition on September 24, 2015.
FOR FURTHER INFORMATION CONTACT: Daniel R. Bushman, Environmental
Analysis Division, Office of Information Analysis and Access (2842T),
Environmental Protection Agency, 1200 Pennsylvania Ave. NW.,
Washington, DC 20460; telephone number: 202-566-0743; fax number: 202-
566-0677; email: [email protected], for specific information on
this notice. For general information on EPCRA section 313, contact the
Emergency Planning and Community Right-to-Know Hotline, toll free at
(800) 424-9346 (select menu option 3) or (703) 412-9810 in Virginia and
Alaska or toll free, TDD (800) 553-7672, http://www.epa.gov/superfund/contacts/infocenter/.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this notice apply to me?
You may be potentially affected by this action if you manufacture,
process, or otherwise use EGBE. Potentially affected categories and
entities may include, but are not limited to:
------------------------------------------------------------------------
Examples of potentially
Category affected entities
------------------------------------------------------------------------
Industry................................ Facilities included in the
following NAICS manufacturing
codes (corresponding to SIC
codes 20 through 39): 311,*
312,* 313,* 314,* 315,* 316,
321, 322, 323,* 324, 325,*
326,* 327, 331, 332, 333,
334,* 335,* 336, 337,* 339,*
111998,* 211112,* 212324,*
212325,* 212393,* 212399,*
488390,* 511110, 511120,
511130, 511140,* 511191,
511199, 512220, 512230,*
519130,* 541712,* or 811490.*
*Exceptions and/or limitations
exist for these NAICS codes.
Facilities included in the
following NAICS codes
(corresponding to SIC codes
other than SIC codes 20
through 39): 212111, 212112,
212113 (correspond to SIC 12,
Coal Mining (except 1241));
or 212221, 212222, 212231,
212234, 212299 (correspond to
SIC 10, Metal Mining (except
1011, 1081, and 1094)); or
221111, 221112, 221113,
221118, 221121, 221122,
221330 (Limited to facilities
that combust coal and/or oil
for the purpose of generating
power for distribution in
commerce) (correspond to SIC
4911, 4931, and 4939,
Electric Utilities); or
424690, 425110, 425120
(Limited to facilities
previously classified in SIC
5169, Chemicals and Allied
Products, Not Elsewhere
Classified); or 424710
(corresponds to SIC 5171,
Petroleum Bulk Terminals and
Plants); or 562112 (Limited
to facilities primarily
engaged in solvent recovery
services on a contract or fee
basis (previously classified
under SIC 7389, Business
Services, NEC)); or 562211,
562212, 562213, 562219,
562920 (Limited to facilities
regulated under the Resource
Conservation and Recovery
Act, subtitle C, 42 U.S.C.
6921 et seq.) (correspond to
SIC 4953, Refuse Systems).
Federal Government...................... Federal facilities.
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This table is not intended to be exhaustive, but rather provides a
guide for readers regarding entities likely to be affected by this
action. Some of the entities listed in the table have exemptions and/or
limitations regarding coverage, and other types of entities not listed
in the table could also be affected. To determine whether your facility
would be affected by this action, you should carefully examine the
applicability criteria in part 372 subpart B of Title 40 of the Code of
Federal Regulations. If you have questions regarding the applicability
of this action to a particular entity, consult the person listed in the
preceding FOR FURTHER INFORMATION CONTACT section.
B. How can I get copies of this document and other related information?
1. Docket. EPA has established a docket for this action under
Docket ID No. EPA-HQ-TRI-2015-0352. Publicly available docket materials
are available either electronically in www.regulations.gov or in hard
copy at the OEI Docket, EPA/DC, EPA West, Room 3334, 1301 Constitution
Ave. NW., Washington, DC. This Docket Facility is open from 8:30 a.m.
to 4:30 p.m., Monday through Friday, excluding legal holidays. The
telephone number for the Public Reading Room is (202) 566-1744, and the
telephone number for the OEI Docket is (202) 566-1752.
2. Electronic Access. You may access this Federal Register document
electronically from the Government Printing Office under the ``Federal
Register'' listings at FDSys (http://www.gpo.gov/fdsys/browse/collection.action?collectionCode=FR).
II. Introduction
Section 313 of EPCRA, 42 U.S.C. 11023, requires certain facilities
that manufacture, process, or otherwise use listed toxic chemicals in
amounts above reporting threshold levels to report their environmental
releases and other waste management quantities of such chemicals
annually. These facilities must also report pollution prevention and
recycling data for such chemicals, pursuant to section 6607 of the PPA,
42 U.S.C. 13106. Congress established an initial list of toxic
chemicals that comprised more than 300 chemicals and 20 chemical
categories.
EPCRA section 313(d) authorizes EPA to add or delete chemicals from
the list and sets criteria for these actions. EPCRA section 313(d)(2)
states that EPA may add a chemical to the list if any of the listing
criteria in Section 313(d)(2) are met. Therefore, to add a chemical,
EPA must demonstrate that at least one criterion is met, but need not
determine whether any other criterion is met. EPCRA section 313(d)(3)
states that a chemical may be deleted if the Administrator determines
there is not sufficient evidence to establish any of the criteria
described in EPCRA section 313(d)(2)(A)-(C). The EPCRA section
313(d)(2)(A)-(C) criteria are:
[[Page 60819]]
The chemical is known to cause or can reasonably be
anticipated to cause significant adverse acute human health effects at
concentration levels that are reasonably likely to exist beyond
facility site boundaries as a result of continuous, or frequently
recurring, releases.
The chemical is known to cause or can reasonably be
anticipated to cause in humans:
[cir] Cancer or teratogenic effects, or
[cir] serious or irreversible--
[ssquf] reproductive dysfunctions,
[ssquf] neurological disorders,
[ssquf] heritable genetic mutations, or
[ssquf] other chronic health effects.
The chemical is known to cause or can be reasonably
anticipated to cause, because of:
[cir] its toxicity,
[cir] its toxicity and persistence in the environment, or
[cir] its toxicity and tendency to bioaccumulate in the
environment,
a significant adverse effect on the environment of sufficient
seriousness, in the judgment of the Administrator, to warrant reporting
under this section.
EPA often refers to the section 313(d)(2)(A) criterion as the
``acute human health effects criterion;'' the section 313(d)(2)(B)
criterion as the ``chronic human health effects criterion;'' and the
section 313(d)(2)(C) criterion as the ``environmental effects
criterion.''
Under section 313(e)(1), any person may petition EPA to add
chemicals to or delete chemicals from the list. EPA issued a statement
of petition policy and guidance in the Federal Register of February 4,
1987 (52 FR 3479) to provide guidance regarding the recommended content
and format for submitting petitions. On May 23, 1991 (56 FR 23703), EPA
issued guidance regarding the recommended content of petitions to
delete individual members of the section 313 metal compounds
categories. EPA published in the Federal Register of November 30, 1994
(59 FR 61432) a statement clarifying its interpretation of the section
313(d)(2) and (d)(3) criteria for modifying the section 313 list of
toxic chemicals.
III. What is the description of the petition?
On January 23, 2015, EPA received a petition from American
Chemistry Council (ACC) Ethylene Glycol Ethers Panel requesting EPA to
delete EGBE (Chemical Abstracts Service Registry Number (CASRN) 111-76-
2) from the list of chemicals subject to reporting under EPCRA section
313 and PPA section 6607 (Reference (Ref. 1)). EGBE is not individually
listed under EPCRA section 313 but rather is reportable under the
Certain Glycol Ethers category. The petitioner contends that the
available scientific data show that EGBE has low potential hazard to
human health and the environment. Therefore, the petitioner believes
that under EPA's policy for listing decisions under EPCRA section 313,
potential exposures should be considered. The petitioner believes that
their analysis shows that exposure levels are well below the concern
levels for human health and ecological effects.
IV. What is EPA's evaluation of the toxicity of EGBE?
EPA's evaluation of the toxicity of EGBE included a review of the
human health and ecological effects data. EPA's Integrated Risk
Information System (IRIS) toxicological review of EBGE (Ref. 2) was the
primary source used to determine the human health effects of EGBE. EPA
also prepared an assessment of the chemistry, fate, and ecological
effects for EGBE (Ref. 3).
A. What is EPA's review of the human health toxicity data for EGBE?
EPA's evaluation of the toxicity of EGBE included a review (Ref. 4)
of the IRIS toxicological review of EGBE (Ref. 2). EPA also reviewed
the findings of studies published since the IRIS toxicological review
of EGBE, but found no data relevant to include in this evaluation. This
Unit outlines the evidence of human health toxicity from the 2010 IRIS
toxicological review of EGBE. Unit IV.B. below discusses the
conclusions regarding EGBE's potential human health toxicity.
1. Toxicokinetics. In humans, EGBE is absorbed and rapidly
distributed following inhalation, ingestion, or dermal exposure (Refs.
5, 6, 7, and 8). Several reviews have described the metabolism of EGBE
in detail (Refs. 9, 10, and 11). The principal products from EGBE
metabolism are butoxyacetic acid (BAA) (rats and humans) and the
glutamine or glycine conjugate of BAA (humans). BAA is excreted in the
urine of both rats and humans, which suggests that the creation of BAA
through the formation of butoxyacetaldehyde by alcohol dehydrogenase is
applicable to rats and humans (Refs. 8, 12, and 13). The other proposed
metabolic pathways, however, may only be applicable to rats since the
metabolites of these pathways (i.e., ethylene glycol, EGBE glucuronide,
and EGBE sulfate) have been observed in the urine of rats (Refs. 14 and
15), but not in humans (Ref. 8). In addition, Corley et al. (Ref. 8)
confirmed the finding from Rettenmeier et al. (Ref. 16) that
approximately two-thirds of the BAA formed in humans is conjugated with
glutamine and glycine. These pathways, however, have not been observed
in the rat.
Several experimental studies have measured the concentration of BAA
in human serum and urine following exposure to EGBE. For humans, the
elimination kinetics of EGBE and BAA appear to be independent of the
route of exposure with an approximate half-life of around one hour for
EGBE and an approximate half-life of BAA of 3-4 hours (Refs. 17, 18,
and 19).
Several physiologically based pharmacokinetic models for EGBE have
been developed. Some older models have described the kinetics of EGBE
for acute human exposure and exposure to rats via the ingestion,
inhalation, and dermal routes (Refs. 17 and 20 based on data from Refs.
13, 21, and 22). Newer models, however, have extended upon the work of
these previous models. Corley et al. (Ref. 7) described the kinetics of
EGBE and BAA in both rats and humans. These authors later validated the
human dermal exposure model (Ref. 8). Lee et al. (Ref. 23) modeled the
kinetics of EGBE and BAA in mice and rats from a National Toxicology
Program (NTP) 2-year inhalation bioassay (based on data from Dill et
al. (Ref. 24)). Species, gender, age, and exposure concentration-
dependent differences in the kinetics of BAA were observed. Corley et
al. (Ref. 12) built on the Lee et al. (Ref. 23) model by replacing some
model assumptions with experimental data (Note: The Corley et al. (Ref.
12) model, along with the Lee et al. (Ref. 23) rat and mouse model and
Corley et al. (Ref. 8) human model were used by EPA to calculate
internal doses of EGBE in the 2010 IRIS toxicological review of EGBE
(Ref. 2)).
2. Effects of Acute and Short-Term Exposure. Hematologic and other
effects have been observed in several acute and short-term oral studies
of EGBE in rats and mice (Refs. 15, 25, 26, 27, 28, 29, 30, 31, 32, 33,
and 34). Varying degrees of hematotoxicity have also been observed in
rats and rabbits following dermal application of EGBE (Refs. 14 and
35). Guinea pigs, however, have not demonstrated sensitivity to the
hematologic effects of EGBE in acute studies (Refs. 36 and 37). EGBE
has also been found to be an ocular irritant when instilled in rabbits
(Refs. 38 and 39).
A few in vitro studies have investigated EGBE's potential hemolytic
effects in human red blood cells after acute exposures. Bartnik et al.
(Ref. 14) reported no hemolysis of human red
[[Page 60820]]
blood cells exposed for three hours to BAA levels up to 15 millimolar
(mM). Hemolysis was observed in rat red blood cells, however, at BAA
levels as low as 1.25 mM. Udden (Ref. 40) incubated human red blood
cells with up to 2.0 mM BBA for four hours, and the authors observed
none of the morphological changes observed in rat red blood cells at
the same concentration. Udden (Ref. 41) reported a significant change
in human red blood cell deformability at exposure to 7.5 and 10 mM BAA
for 4 hours, whereas deformability in rat red blood cells was
significantly increased at 0.05 mM BAA. Mean cellular volume in human
blood samples was significantly increased at 10 mM BAA while mean
cellular volume in rats was significantly increased at 0.05 mM BAA.
There are a number of case reports of acute ingestion of EGBE with
little or no hematologic effects observed (Refs. 42, 43, 44, 45, 46,
47, 48, and 49). Some other observed effects were likely not directly
related to hemolysis; however, the cause of the effects cannot be
explained based on the limited data available. Also, hemodialysis was
employed to remove un-metabolized EGBE in many of the cases.
One experimental study in humans (Ref. 50), observed no effects on
red blood cell fragility after exposure of two males and one female to
up to 195 part per million (ppm) EGBE for 8 hours.
3. Carcinogenicity and Mutagenicity. Under the Guidelines for
Carcinogen Risk Assessment (Ref. 51), there is suggestive evidence of
EGBE's carcinogenic potential based on a 2-year NTP bioassay in mice
and rats (Ref. 52). EGBE has been tested for its potential for
genotoxicity both in vitro and in vivo, and the available data do not
demonstrate that EGBE is mutagenic or clastogenic (Refs. 53, 54, 55,
56, 57, and 58).
4. Reproductive and Developmental Toxicity. The reproductive and
developmental toxicity of EGBE has been investigated in a number of
oral and inhalation studies in rats, mice, and rabbits. In a two-
generation reproductive toxicity study, fertility was reduced in mice
at very high maternally toxic doses (>1,000 milligrams/kilogram (mg/
kg)) (Ref. 59), but no other significant reproductive effects were
reported in any study (Refs. 26, 52, 60, 61, 62, 63, 64, 65, and 66).
Maternal toxicity related to the hematologic effects of EGBE and
relatively minor developmental effects have been reported in
developmental studies (Refs. 67, 68, 69, and 70). No teratogenic
effects were noted in any of the studies. As such, EGBE is not
reasonably anticipated to be a reproductive or developmental toxicant
at moderately low to low doses.
5. Neurotoxicity. There is no evidence of neurotoxicity in any
animal studies of EGBE. One case study patient demonstrated neurologic
deficits after ingesting a product with a high dose of EGBE and other
chemicals (Ref. 47). Given the general limitations of case studies and
the presence of other chemicals, however, EPA cannot draw conclusions
about EGBE's potential neurotoxicity from this particular study.
6. Other Subchronic and Chronic Toxicity. Hematologic effects and
liver toxicity have been observed at low doses of EGBE in several
animal studies.
The NTP (Ref. 66) conducted a 13-week study in F344 rats and B6C3F1
mice in which groups of 10 animals/gender/species received EGBE in
drinking water at doses of 0, 750, 1,500, 3,000, 4,500, and 6,000 ppm.
The corresponding doses based on measured drinking water consumption
were: 0, 69, 129, 281, 367, or 452 milligrams/kilogram/day (mg/kg/day)
in male rats; 0, 82, 151, 304, 363, or 470 mg/kg/day in female rats; 0,
118, 223, 553, 676, or 694 mg/kg/day in male mice; and 0, 185, 370,
676, 861, or 1,306 mg/kg/day in female mice.
Indications of mild to moderate anemia were observed in both
genders. Statistically significant hematologic effects in female rats
included reduced red blood cell counts and hemoglobin concentrations at
>=750 ppm and increased reticulocytes, decreased platelets, and
increased bone marrow cellularity at 3,000 ppm. Liver effects including
cytoplasmic alterations, hepatocellular degeneration, and pigmentation
were reported in the mid- and high-dose groups (>=1,500 ppm for males
and females; statistics not reported). Additionally, cytoplasmic
alterations of liver hepatocytes were observed in the lowest-dose
groups (750 ppm for males and females). The lack of cytoplasmic
granularity of the hepatocytes indicates that this response was not due
to enzyme induction (Ref. 71). The NTP (Ref. 66) identified a lowest-
observed-adverse-effect level (LOAEL) for rats of 750 ppm
(approximately 58.6 mg/kg/day calculated using water consumption rates
and body weights measured during the last week of exposure and,
therefore, slightly different from those reported by the study authors
(Ref. 2)) based on decreased red blood cell count and hemoglobin in
female rats. A NOAEL was not identified.
A reduction in body weight gain at >=3,000 ppm was observed in male
and female mice. An increase in relative kidney weight was also
observed at all doses in female mice. Body weight reductions followed
decreased water consumption. No histopathologic changes were noted at
any dose level, however, relative kidney weights showed a statistically
significant increase at 750 and 1,500 ppm in the absence of reduction
in body weight gain. The NTP (Ref. 66) identified a LOAEL for mice of
3,000 ppm (approximately, 553-676 mg/kg/day calculated using water
consumption rates and body weights measured during the last week of
exposure and, therefore, slightly different from those reported by the
study authors (Ref. 2)) based on reduced body weight and body weight
gain.
Dodd et al. (Ref. 62) conducted a 90-day subchronic inhalation
study using F344 rats (16/gender/group) exposed to EGBE for 6 hours/
day, 5 days/week at concentrations of 0, 5, 25, and 77 ppm. After 6
weeks, the 77 ppm female rats had statistically significant decreases
in red blood cell counts (13%) and hemoglobin concentrations,
accompanied by an 11% increase in mean corpuscular hemoglobin. Similar
results were observed in males. However, many of these effects had
lessened by the end of the study. The authors reported a LOAEL of 77
ppm based on decreases in red blood cell count and hemoglobin
concentrations, accompanied by an increase in mean corpuscular
hemoglobin in both genders.
The NTP (Ref. 52) conducted a subchronic inhalation study in F344
rats and B6C3F1 mice (10/gender). Rats and mice were exposed to EGBE
concentrations of 0, 31, 62.5, 125, 250, and 500 ppm (0, 150, 302, 604,
1,208, and 2,416 milligrams/cubic meter (mg/m\3\)) 6 hours/day, 5 days/
week for 14 weeks. The NTP (Ref. 52) identified a LOAEL of 31 ppm in
female rats based on decreases in hematocrit, hemoglobin, and red blood
cell count and a LOAEL of 62.5 ppm in male rats based on a decrease in
red blood cell count. Histopathologic effects were observed in male and
female rats. Effects reported in female rats included liver necrosis at
250 ppm and centrilobular degeneration and renal tubular degeneration
at 500 ppm. Other effects reported in both genders included: Excessive
splenic congestion in the form of extramedullary hematopoiesis (at 250
ppm in male rats and 125 ppm in female rats), hemosiderin accumulation
in Kupffer cells (at 125 ppm in male rats and 62.5 ppm in female rats),
intracytoplasmic hemoglobin (at 125 ppm in male rats and 31 ppm in
female rats), hemosiderin deposition (at 125 ppm in male rats and 62.5
ppm in
[[Page 60821]]
female rats), and bone marrow hyperplasia (at 250 ppm in male rats and
62.5 ppm in female rats). The authors identified a LOAEL of 62.5 ppm
for mice based on histopathological changes in the forestomach
(including: Necrosis, ulceration, inflammation, and epithelial
hyperplasia) in both males and females. Signs consistent with the
hemolytic effects of EGBE (including: Decreased red blood cell counts,
increased reticulocyte counts, and increased mean corpuscular volume)
were also observed at 250 and 500 ppm in male and female mice.
The NTP (Ref. 52) also completed a 2-year inhalation study on EGBE
in both F344 rats and B6C3F1 mice. In this study, animals were exposed
to EGBE 6 hours/day, 5 days/week at concentrations of 0, 31, 62.5, and
125 ppm (0, 150, 302, and 604 mg/m\3\) for groups of 50 F344 rats and
0, 62.5, 125, and 250 ppm (0, 302, 604, and 1,208 mg/m\3\) for groups
of 50 B6C3F1 mice. The authors identified a LOAEL of 31 ppm in rats
based on decreases in hematocrit, hemoglobin, and red blood cell count
in female rats in a satellite group observed at 3 and 6 months. The
authors identified 62.5 ppm as the LOAEL for mice based on hemosiderin
deposition.
One long-term occupational study of EGBE was identified in the
literature. Haufroid et al. (Ref. 72) reported a small decrease in
hematocrit and increase in mean corpuscular hemoglobin in a cross
sectional study of 31 workers exposed to an average concentration of
0.6 ppm EGBE over 1 to 6 years. The biological significance of these
findings, however, is unclear as they were within normal clinical
ranges and no other measured parameters were affected by EGBE exposure.
B. What are EPA's conclusions regarding the human hazard potential of
EGBE?
There is evidence to indicate that the human red blood cell
response to EGBE exposure is less than that of rodents, however, this
conclusion is based on a relatively small number of in vitro and short-
term human exposure studies with supporting evidence from
pharmacokinetic models (Refs. 7, 8, 14, 40, 41, and 50). Little is
known of the long-term or repeated exposure responses in humans to
EGBE.
In 2010, EPA concluded in the IRIS toxicological review of EGBE
that human red blood cells do appear capable of responding similarly to
the causative EGBE metabolites, albeit at much higher exposures (Ref.
2). The IRIS toxicological review of EGBE employed an interspecies
uncertainty factor of 1 to derive the reference values for EGBE in part
because there was not a preponderance of toxicodynamic data in both
animals and humans describing why humans are less sensitive than rats
to the hematologic effects in question (Ref. 2). Also, EPA calculated a
human equivalent concentration LOAEL (LOAELHEC) for
hematologic effects of 271 mg/m\3\ (approximately 77 mg/kg/day,
assuming constant exposure, an inhalation rate of 20 cubic meters/day
(m\3\/day), and a 70 kg human) using pharmacokinetic model estimates
(Refs. 7 and 8) of the human internal dose equivalent of the toxic
metabolite BAA to that estimated for female rats exposed to 31 ppm EGBE
in the NTP (Ref. 52) study (Ref. 2). In its assessment of EGBE, the
European Union carried out a slightly different calculation based on
the same underlying data and reported a similar, but slightly higher,
human equivalent LOAEL of 474 mg/m\3\ (approximately 135 mg/kg/day)
(Ref. 11).
Additionally, multiple animal studies by the NTP reported liver
toxicity (e.g., cytoplasmic alterations of liver hepatocytes at 750 ppm
(approximately 69 mg/kg/day) in male rats and 750 ppm (82 mg/kg/day) in
female rats (Ref. 66) and liver necrosis at 250 ppm (approximately 243
mg/kg/day) in female rats (Ref. 52)) to which humans do not demonstrate
decreased sensitivity. These findings provide further evidence of
EGBE's potential toxicity to humans at moderately low to low doses.
Therefore, the available evidence is sufficient to conclude that
EGBE can be reasonably anticipated to demonstrate moderately high to
high chronic toxicity in humans based on the EPCRA Section 313 listing
criteria (59 FR 61432, November 30, 1994).
C. What is EPA's review of the ecological toxicity of EGBE?
Based on a review of the available aquatic ecological toxicity
data, EGBE does not appear to present a significant concern for adverse
effects on the environment. Experimentally measured effects occurred at
relatively high concentrations indicating low toxicity (Ref. 3). Such
high concentrations are not expected to be observed under typical
environmental conditions. Table 1 presents some of the available
toxicity data for EGBE, the complete listing of the available toxicity
data and more details about the studies can be found in the ecological
assessment (Ref. 3).
1. Acute toxicity. Toxicity threshold values (duration not
specified) of 900 milligrams/liter (mg/L) and 72-hour EC50
values (i.e., the concentration that is effective in producing a
sublethal response in 50% of test organisms) of 911 and 1,840 mg/L for
biomass and growth rate, respectively, have been reported for green
algae (Refs. 73, 74, and 75). The corresponding 72-hour No-Observed-
Effect-Concentration (NOEC) values for biomass and growth rate were 88
and 286 mg/L (Ref. 76). For water fleas (Daphnia magna), 24- or 48-hour
EC50 values ranged from 835 to 1,815 mg/L (Refs. 77 and 78).
A 48-hour EC50 value of 164 mg/L in rotifers (reproduction)
has also been reported (Refs. 74 and 75).
Acute toxicity values for freshwater fish ranged from an
LC50 (i.e., the concentration that is lethal to 50% of test
organisms) of 1,395 mg/L for the golden orfe (Leuciscus idus) (duration
not specified) (Ref. 79) to a 96-hour LC50 of 2,137 mg/L for
the fathead minnow (Pimephales promelas) (Ref. 80). A 96-hour
LC50 value of 1,490 mg/L was available for bluegill sunfish
(Ref. 81) and 96-hour LC50 values for rainbow trout were
1,474 and 1,700 mg/L (Refs. 74, 75, and 82). An LC50 value
(duration not specified) of 1,575 mg/L was also available for golden
orfe (Leuciscus idus) (Ref. 79) and a 24-hour LC50 value of
1,700 mg/L was available for goldfish (Carassius auratus) (Ref. 83).
A study of the invertebrate Artemia salina (brine shrimp) reported
a 24-hour LC50 value of 1,000 mg/L (Ref. 84). Also, an
embryo-larval test in which Japanese oyster eggs (Crassostrea gigas)
were incubated with the test material for 24 hours and then examined
for abnormalities indicated an identical 24-hour Lowest-Observed-
Effect-Concentration (LOEC) of 1,000 mg/L (Ref. 74). A study of an
estuarine/marine fish silverside (Menidia beryllina) reported a 96-hour
LC50 value of 1,250 mg/L (Ref. 81).
2. Chronic toxicity. Values for chronic toxicity in aquatic plants
ranged from an 8-day LOEC (inhibition of cell division) of 35 mg/L for
the cyanobacteria Microcystis aeruginosa (Refs. 85 and 86) to greater
than 1,000 mg/L for a 7-day EC50 (growth rate) for the green
alga Selenastrum capricornutum (Ref. 87). Experimental data for the
freshwater invertebrate Daphnia magna include values that ranged from
100 mg/L for a 21-day NOEC (reproduction) (Refs. 74, 75, and 77) to an
EC50 of 297 mg/L (endpoint not reported) (Ref. 88).
[[Page 60822]]
Table 1--Range of Experimental Ecological Toxicity Values for EGBE on Selected Target Species
----------------------------------------------------------------------------------------------------------------
Duration and Experiment type
Species test endpoint \a\ Value (mg/L) Reference
----------------------------------------------------------------------------------------------------------------
Acute aquatic toxicity
----------------------------------------------------------------------------------------------------------------
Algae:
Green algae 72-hour EC50 S, M............ 1,840 (Refs. 74 and 75).
(Pseudokirchneriella (growth).
subcapitata).
Green algae 72-hour NOEC S, M............ 88 (Ref. 82).
(Pseudokirchneriella (biomass).
subcapitata).
Freshwater invertebrate:
Water flea (Daphnia 48-hour EC50.... S, U, O......... 1,815 (Ref. 78).
magna).
Rotifer (Brachionus 48-hour EC50 S, M............ 164 (Refs. 74 and 75).
calyciflorus). (reproduction).
Freshwater fish:
Golden orfe (Leuciscus LC50............ NS.............. 1,395 (Ref. 79).
idus).
Fathead minnow 96-hour LC50.... S, O............ 2,137 (Ref. 80).
(Pimephales promelas).
Estuarine/marine
invertebrate:
Brine shrimp (Artemia 24-hour LC50.... S, U, C......... 1,000 (Ref. 84).
salina).
Japanese oyster eggs 24-hr LOEC S............... 1,000 (Refs. 74 and 75).
(Crassostrea gigas). (embryotoxicity
).
Estuarine/marine fish:
Silverside (Menidia 96-hour LC50.... S, U............ 1,250 (Ref. 81).
beryllina).
----------------------------------------------------------------------------------------------------------------
Chronic aquatic toxicity
----------------------------------------------------------------------------------------------------------------
Algae:
Blue-green algae 8-day LOEC (cell S, U............ 35 (Refs. 85 and 86).
(Microcystis aeruginosa). multiplication
inhibition).
Green algae (Selenastrum 7-day EC50 S, U............ >1,000 (Ref. 87).
capricornutum). (growth rate).
Freshwater invertebrate:
Water flea (Daphnia 21-day NOEC R, M............ 100 (Refs. 74 and 75).
magna). (reproduction).
Water flea (Daphnia 21-day NOEC..... R, M............ 100 (Ref. 88).
magna).
Water flea (Daphnia 21-day EC50..... R, M............ 297 (Ref. 88).
magna).
Freshwater fish:
Zebrafish (Brachydanio 21-day NOEC NS.............. >100 (Ref. 89).
rerio). (mortality).
----------------------------------------------------------------------------------------------------------------
a Experiment type: S = static, R = renewal, M = measured, U = unmeasured, O = open test system, NS = not
specified
V. What is EPA's rationale for the denial?
EPA is denying the petition to delete EGBE from the Certain Glycol
Ethers category which is subject to reporting under EPCRA section 313.
This denial is based on EPA's conclusion that EGBE can reasonably be
anticipated to cause serious or irreversible chronic health effects in
humans, specifically, liver toxicity and concerns for hematological
effects. While EPA acknowledges that there is evidence to indicate that
humans are less sensitive than rodents to the hematological effects
associated with acute or short-term exposure to EGBE, little is known
of the long-term or repeated exposure responses in humans to EGBE.
Thus, some concern remains over the potential for hematological effects
following a lifetime of exposure to EGBE. Unlike the hematological
effects of EGBE, there is no evidence of humans' decreased sensitivity
to the reported liver effects relative to rodents. Therefore, EPA has
concluded that EGBE meets the EPCRA section 313(d)(2)(B) listing
criteria based on the available human health toxicity data.
Because EPA believes that EGBE has moderately high to high chronic
toxicity, EPA does not believe that an exposure assessment is
appropriate for determining whether EGBE meets the criteria of EPCRA
section 313(d)(2)(B). This determination is consistent with EPA's
published statement clarifying its interpretation of the section
313(d)(2) and (d)(3) criteria for modifying the section 313 list of
toxic chemicals (59 FR 61432, November 30, 1994).
VI. References
EPA has established an official public docket for this action under
Docket ID No. EPA-HQ-TRI-2015-0352. The public docket includes
information considered by EPA in developing this action, including the
documents listed below, which are electronically or physically located
in the docket. In addition, interested parties should consult documents
that are referenced in the documents that EPA has placed in the docket,
regardless of whether these referenced documents are electronically or
physically located in the docket. For assistance in locating documents
that are referenced in documents that EPA has placed in the docket, but
that are not electronically or physically located in the docket, please
consult the person listed in the above FOR FURTHER INFORMATION CONTACT
section.
1. American Chemistry Council. 2014. Petition of the American
Chemistry Council's Ethylene Glycol Ethers Panel To Remove Ethylene
Glycol Monobutyl Ether From the Toxics Release Inventory Under
Section 313 Of The Emergency Planning and Community Right-To-Know
Act of 1986. December 29, 2014.
2. U.S. EPA. 2010. Toxicological review of Ethylene Glycol Monobutyl
Ether (CASRN 111-76-2) in support of summary information on the
Integrated Risk Information System (IRIS). U.S. Environmental
Protection Agency. Washington, DC. http://www.epa.gov/iris/toxreviews/0500tr.pdf.
3. U.S. EPA. 2009. Technical Review of Ethylene Glycol Monobutyl
Ether (EGBE): Chemistry, Environmental Fate and Ecological Toxicity
CAS Registry Number 111-76-2. Office of Environmental Information.
September 9, 2009.
4. U.S. EPA. 2015. Memorandum from Jocelyn Hospital, Toxicologist,
Environmental Analysis Division to Megan Carroll, Acting Division
Director of the Environmental Analysis Division. July 24, 2015.
Subject: Review of the Data in the 2010 Integrated Risk Information
System (IRIS) Toxicological
[[Page 60823]]
Review of Ethylene Glycol Monobutyl Ether (EGBE).
5. Kumagai, S., Oda H., Matsunaga I., Kosaka H., Akasaka S. 1999.
Uptake of 10 polar organic solvents during short-term respiration.
Toxicol. Sci. 48: 255-263.
6. Johanson G., Boman A. 1991. Percutaneous absorption of 2-
butoxyethanol vapour in human subjects. Occup. Environ. Med. 48:
788-792.
7. Corley R.A., Bormett G.A., Ghanayem B.I. 1994. Physiologically-
based pharmacokinetics of 2-butoxyethanol and its major metabolite
2-butoxyacetic acid, in rats and humans. Toxicol. Appl. Pharmacol.
129: 61-79.
8. Corley R.A., Markham D.A., Banks C., Delorme P., Masterman A.,
Houle J.M. 1997. Physiologically based pharmacokinetics and the
dermal absorption of 2-butoxyethanol vapor by humans. Fundam. Appl.
Toxicol. 39: 120-130.
9. Commonwealth of Australia. 1996. National Industrial Chemicals
Notification and Assessment Scheme (NICNAS)-priority existing
chemical no. 6-2-butoxyethanol in cleaning products. Australian
Government Publishing Service. Canberra, Australia. http://www.nicnas.gov.au/__data/assets/pdf_file/0003/4368/PEC_6_2-Butoxyethanol-in-Cleaning-Products_Full_Report_PDF.pdf.
10. ECETOC. 1994. Butoxyethanol criteria document. Special Report
No. 7. European Centre for Ecotoxicology and Toxicology of
Chemicals. Brussels, Belgium.
11. E.U. 2006. European Union Risk Assessment Report: 2-
butoxyethanol. http://echa.europa.eu/documents/10162/e74a38e1-b9e1-4568-92c5-615c4b56f92d.
12. Corley, R.A., Grant, D.M., Farris, E., Weitz, K.K., Soelberg,
J.J., Thrall, K.D., Poet, T.S. 2005. Determination of age and gender
differences in biochemical processes affecting the disposition of 2-
butoxyethanol and its metabolites in mice and rats to improve PBPK
modeling. Toxicol. Lett. 156: 127-161.
13. Medinsky, M.A., Singh, G., Bechtold, W.E., Bond, J.A., Sabourin,
P.J., Birnbaum, L.S., Henderson, R.F. 1990. Disposition of three
glycol ethers administered in drinking water to male F344/N rats.
Toxicol. Appl. Pharmacol. 102: 443-455.
14. Bartnik, F.G., Reddy, A.K., Klecak, G., Zimmermann, V.,
Hostynek, J.J., Kunstler, K. 1987. Percutaneous absorption,
metabolism, and hemolytic activity of n-butoxyethanol. Fundam. Appl.
Toxicol. 8: 59-70.
15. Ghanayem, B.I., Blair, P.C., Thompson, M.B., Maronpot, R.R.,
Matthews, H.B. 1987. Effect of age on the toxicity and metabolism of
ethylene glycol monobutyl ether (2-butoxyethanol) in rats. Toxicol.
Appl. Pharmacol. 91: 222-234.
16. Rettenmeier, A.W., Hennigs, R., Wodarz, R. 1993. Determination
of butoxyacetic acid and N-butoxyacetyl-glutamine in urine of
lacquerers exposed to 2-butoxyethanol. Int. Arch. Occup. Environ.
Health. 65: S151-S153.
17. Johanson, G. 1986. Physiologically based pharmacokinetic
modeling of inhaled 2-butoxyethanol in man. Toxicol. Lett. 34: 23-
31.
18. Johanson, G., Johnsson, S. 1991. Gas chromatographic
determination of butoxyacetic acid in human blood after exposure to
2-butoxyethanol. Arch. Toxicol. 65: 433-435.
19. Johanson, G., Boman, A., Dynesius, B. 1988. Percutaneous
absorption of 2-butoxyethanol in man. Scand. J. Work Environ.
Health. 14: 101-109.
20. Shyr, L.J., Sabourin, P.J., Medinsky, M.A., Birnbaum, L.S.,
Henderson, R.F. 1993. Physiologically based modeling of 2-
butoxyethanol disposition in rats following different routes of
exposure. Environ. Res. 63: 202-218.
21. Sabourin, P.J., Medinsky, M.A., Birnbaum, L.S., Griffith, W.C.,
Henderson, R.F. 1992. Effect of exposure concentration on the
disposition of inhaled butoxyethanol by F344 rats. Toxicol. Appl.
Pharmacol. 114: 232-238.
22. Sabourin, P.J., Medinsky, M.A., Thurmond, F., Birnbaum, L.S.,
Henderson, R.F. 1993. Erratum to: Effect of dose on the disposition
of methoxyethanol, ethoxyethanol, and butoxyethanol administered
dermally to male F344/N rats. Fundamental and Applied Toxicology
19:124-132. Fundam. Appl. Toxicol. 20: 508-510.
23. Lee, K.M., Dill, J.A., Chou, B.J., Roycroft, J.H. 1998.
Physiologically based pharmacokinetic model for chronic inhalation
of 2-butoxyethanol. Toxicol. Appl. Pharmacol. 153: 211-226.
24. Dill, J.A., Lee, K.M., Bates, D.J., Anderson, D.J., Johnson,
R.E., Chou, B.J., Burka, L.T., Roycroft, J.H. 1998. Toxicokinetics
of inhaled 2-butoxyethanol and its major metabolite, 2-butoxyacetic
acid, in F344 rats and B6C3F1 mice. Toxicol. Appl. Pharmacol. 153:
227-242.
25. Ghanayem, B.I., Sullivan, C.A. 1993. Assessment of the
haemolytic activity of 2-butoxyethanol and its major metabolite,
butoxyacetic acid, in various mammals including humans. Hum. Exp.
Toxicol. 12: 305-311.
26. Grant, D., Sulsh, S., Jones, H.B., Gangolli, S.D., Butler, W.H.
1985. Acute toxicity and recovery in the hemopoietic system of rats
after treatment with ethylene glycol monomethyl and monobutyl
ethers. Toxicol. Appl. Pharmacol. 77: 187-200.
27. Ghanayem, B.I., Sanchez, I.M., Matthews, H.B. 1992. Development
of tolerance to 2-butoxyethanol-induced hemolytic anemia and studies
to elucidate the underlying mechanisms. Toxicol. Appl. Pharmacol.
112: 198-206.
28. Ezov, N., Levin-Harrus, T., Mittelman, M., Redlich, M., Shabat,
S., Ward, S.M., Peddada, S., Nyska, M., Yedgar, S., Nyska, A. 2002.
A chemically induced rat model of hemolysis with disseminated
thrombosis. Cardiovasc. Toxicol. 2: 181-194.
29. Koshkaryev, A., Barshtein, G., Nyska, A., Ezov, N., Levin-
Harrus, T., Shabat, S., Nyska, M., Redlich, M., Tsipis, F., Yedgar,
S. 2003. 2-Butoxyethanol enhances the adherence of red blood cells.
Arch. Toxicol. 77: 465-469.
30. Shabat, S., Nyska, A., Long, P.H., Goelman, G., Abramovitch, R.,
Ezov, N., Levin-Harrus, T., Peddada, S., Redlich, M., Yedgar, S.,
Nyska, M. 2004. Osteonecrosis in a chemically induced rat model of
human hemolytic disorders associated with thrombosis--a new model
for avascular necrosis of bone. Calcif. Tissue Int. 74: 220-228.
31. Redlich, M., Maly, A., Aframian, D., Shabat, S., Ezov, N.,
Levin-Harrus, T., Nyska, M., Nyska, A. 2004. Histopathologic changes
in dental and oral soft tissues in 2-butoxyethanol-induced hemolysis
and thrombosis in rats. J. Oral. Pathol. Med. 33: 424-429.
32. Corley, R.A; Weitz, K.K., Mast, T.J., Miller, R.A., Thrall, B.D.
1999. Short-term studies to evaluate the dosimetry and modes of
action of EGBE in B6C3F1 mice [final report]. Battelle Memorial
Institute. Richland, WA. Battelle Project No. 29753.
33. Poet, T.S., Soelberg, J.J., Weitz, K.K., Mast, T.J., Miller,
R.A., Thrall, B.D., Corley, R.A. 2003. Mode of action and
pharmacokinetic studies of 2-butoxyethanol in the mouse with an
emphasis on forestomach dosimetry. Toxicol. Sci. 71: 176-189.
34. Green, T; Toghill A; Lee R; Moore R; Foster J. 2002. The
development of forestomach tumors in the mouse following exposure to
2-butoxyethanol by inhalation: Studies on the mode of action and
relevance to humans. Toxicology. 180: 257-273.
35. Tyler, T.R. 1984. Acute and subchronic toxicity of ethylene
glycol monobutyl ether. Environ. Health. Perspect. 57: 185-191.
36. Shepard, K.P. 1994. Ethylene glycol monobutyl ether: Acute oral
toxicity study in the guinea pig. Eastman Kodak Company for Chemical
Manufacturers Association. Rochester, NY and Arlington, VA.
37. Gingell, R., Boatman, R.J., Lewis, S. 1998. Acute toxicity of
ethylene glycol mono-n-butyl ether in the guinea pig. Food Chem.
Toxicol. 36: 825-829.
38. Jacobs, G.A., Martens, M.A. 1989. An objective method for the
evaluation of eye irritation in vivo. Food Chem. Toxicol. 27: 255-
258.
39. Kennah, H.E. II., Hignet, S., Laux, P.E., Dorko, J.D., Barrow,
C.S. 1989. An objective procedure for quantitating eye irritation
based upon changes of corneal thickness. Fundam. Appl. Toxicol. 12:
258-268.
40. Udden, M.M. 2000. Rat erythrocyte morphological changes after
gavage dosing with 2-butoxyethanol: A comparison with the in vitro
effects of butoxyacetic acid on rat and human erythrocytes. J. Appl.
Toxicol. 20: 381-387.
41. Udden, M.M. 2002. In vitro sub-hemolytic effects of butoxyacetic
acid on human and rat erythrocytes. Toxicol. Sci. 69: 258-264.
[[Page 60824]]
42. Bauer, P., Weber, M., Mur, J.M., Protois, J.C., Bollaert, P.E.,
Condi, A., Larcan, A., Lambert, H. 1992. Transient non-cardiogenic
pulmonary edema following massive ingestion of ethylene glycol butyl
ether. Intensive Care Med. 18: 250-251.
43. Gijsenbergh, F.P., Jenco, M., Veulemans, H., Groeseneken, D.,
Verberckmoes, R., Delooz, H.H. 1989. Acute butylglycol intoxication:
A case report. Hum. Toxicol. 8: 243-245.
44. Gualtieri, J.F., Harris, C.R., Roy, R., Corley, R.A.,
Manderfield, C. 1995. Multiple 2-butoxyethanol intoxications in the
same patient: Clinical findings, pharmacokinetics, and therapy. J.
Toxicol. Clin. Toxicol. 33: 550-551.
45. Gualtieri, J.F., DeBoer, L., Harris, C.R., Corley, R. 2003.
Repeated ingestion of 2-butoxyethanol: Case report and literature
review. J. Toxicol. Clin. Toxicol. 41: 57-62.
46. Rambourg-Schepens, M.O., Buffet, M., Bertault. R., Jaussaud, M.,
Journe, B., Fay, R., Lamiable, D. 1988. Severe ethylene glycol butyl
ether poisoning. Kinetics and metabolic pattern. Hum Toxicol, 7:
187-189.
47. Burkhart, K.K., Donovan, J.W. 1998. Hemodialysis following
butoxyethanol ingestion. Clin. Toxicol. 36: 723-725.
48. Osterhoudt, K.C. 2002. Fomepizole therapy for pediatric
butoxyethanol intoxication. J. Toxicol. Clin. Toxicol. 40: 929-930.
49. Dean, B.S., Krenzelok, E.P. 1991. Critical evaluation of
pediatric ethylene glycol monobutyl ether poisonings. Vet. Hum.
Toxicol. 33: 362.
50. Carpenter, C.P., Pozzani, U.C., Weil, C.S., Nair III, J.H.,
Keck, G.A., Smyth Jr., H.F. 1956. The toxicity of butyl cellosolve
solvent. AMA Arch. Ind. Health. 14: 114-131.
51. U.S. EPA. 2005. Guidelines for carcinogen risk assessment, Final
Report. Risk Assessment Forum, U.S. Environmental Protection Agency.
Washington, DC. EPA/630/P-03/001F. http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=116283.
52. NTP. 2000. NTP technical report on the toxicology and
carcinogenesis studies of 2 butoxyethanol (CAS No. 111-76-2) in
F344/N rats and B6C3F1 mice (inhalation studies). National
Toxicology Program. Research Triangle Park, NC. NTP TR 484. http://ntp.niehs.nih.gov/?objectid=070AC403-B110-CA79-3A23AF79DE7B752A.
53. Zeiger, E., Anderson, B., Haworth, S., Lawlor, T., Mortelmans,
K. 1992. Salmonella mutagenicity tests: V Results from the testing
of 311 chemicals. Environ. Mol. Mutagen. 19: 2-141.
54. Gollapudi, B.B., Barber, E.D., Lawlor, T.E., Lewis, S.A. 1996.
Re-examination of the mutagenicity of ethylene glycol monobutyl
ether to Salmonella tester strain TA97a. Mutat. Res. 370: 61-64.
55. Chiewchanwit, T., Au, W.W. 1995. Mutagenicity and cytotoxicity
of 2-butoxyethanol and its metabolite, 2-butoxyacetaldehyde, in
Chinese hamster ovary (CHO-AS52) cells. Mutat. Res. 334: 341-346.
56. Klaunig, J.E., Kamendulis, L.M. 2005. Mode of action of
butoxyethanol-induced mouse liver hemangiosarcomas and
hepatocellular carcinomas. Toxicol. Lett. 156: 107-115.
57. NTP. 1996. Toxicology and carcinogenesis studies of acetonitrile
(CAS No 75-05-8) in F344/N rats and B6C3F1 mice (inhalation
studies). National Toxicology Program. Research Triangle Park, NC.
http://ehp.niehs.nih.gov/ntp/docs/4004xxdoc.html.
58. Keith, G., Coulais, C., Edorh, A., Bottin, M.C., Rihn, B. 1996.
Ethylene glycol monobutyl ether has neither epigenetic nor genotoxic
effects in acute treated rats and in subchronic treated v-HA-ras
transgenic mice. Occup. Hyg. 2: 237-249.
59. Heindel, J.J., Gulati, D.K., Russell, V.S., Reel, J.R., Lawton,
AD., Lamb IV, J.C. 1990. Assessment of ethylene glycol monobutyl and
monophenyl ether reproductive toxicity using a continuous breeding
protocol in Swiss CD-1 Mice. Fundam. Appl. Toxicol. 15: 683-696.
60. Nagano, K., Nakayama, E., Koyano, M., Oobayashi, H., Adachi, H.,
Yamada, T. 1979. Testicular atrophy of mice induced by ethylene
glycol mono alkyl ethers (author's translation). Sangyo Igaku/Jap.
J. Ind. Health. 21: 29-35.
61. Nagano, K., Nakayama, E., Oobayashi, H., Nishizawa, T., Okuda,
H., Yamazaki, K. 1984. Experimental studies on toxicity of ethylene
glycol alkyl ethers in Japan. Environ. Health. Perspect. 57: 75-84.
62. Dodd, D.E., Snellings, W.M., Maronpot, R.R., Ballantyne, B.
1983. Ethylene glycol monobutyl ether: Acute, 9-day, and 90-day
vapor inhalation studies in Fischer 344 rats. Toxicol. Appl.
Pharmacol. 68: 405-414.
63. Doe, J.E. 1984. Further studies on the toxicology of the glycol
ethers with emphasis on rapid screening and hazard assessment.
Environ. Health Perspect. 57: 199-206.
64. Foster, P.M., Lloyd, S.C., Blackburn, D.M. 1987. Comparison of
the in vivo and in vitro testicular effects produced by methoxy-,
ethoxy- and N-butoxy acetic acids in the rat. Toxicology. 43: 17-30.
65. Exon, J.H., Mather, G.G., Bussiere, J.L., Olson, D.P., Talcott,
P.A. 31991. Effects of subchronic exposure of rats to 2-
methoxyethanol or 2-butoxyethanol: Thymic atrophy and
immunotoxicity. Fundam. Appl. Toxicol. 16: 830-840.
66. NTP. 1993. NTP technical report on toxicity studies of ethylene
glycol ethers: 2-methoxyethanol, 2-ethoxyethanol, 2-butoxyethanol
(CAS Nos. 109-86-4, 110-80-5, 111-76-2) administered in drinking
water to F344/N rats and B6C3F1 mice. National Toxicology Program.
Research Triangle Park, NC. 26; NIH Publication 93-3349.
67. Nelson. B.K., Setzer, J.V., Brightwell, W.S., Mathinos, P.R.,
Kuczuk, M.H., Weaver, T.E., Goad, P.T. 1984. Comparative inhalation
teratogenicity of four glycol ether solvents and an amino derivative
in rats. Environ. Health Perspect. 57: 261-271.
68. Tyl, R.W., Millicovsky, G., Dodd, D.E., Pritts, I.M., France,
K.A., Fisher, L.C. 1984. Teratologic evaluation of ethylene glycol
monobutyl ether in Fischer 344 rats and New Zealand white rabbits
following inhalation exposure. Environ. Health Perspect. 57: 47-68.
69. Hardin, B.D., Goad, P.T., Burg, J.R. 1984. Developmental
toxicity of four glycol ethers applied cutaneously to rats. Environ.
Health Perspect. 57: 69-74.
70. Wier, P.J., Lewis, S.C., Traul, K.A. 1987. A comparison of
developmental toxicity evident at term to postnatal growth and
survival using ethylene glycol monoethyl ether, ethylene glycol
monobutyl ether, and ethanol. Teratog. Carcinog. Mutagen. 7: 55-64.
71. Greaves, P. 2000. Hepatocellular hypertrophy and hyperplasia. In
Histopathology of preclinical toxicity studies: Interpretation and
relevance in drug safety evaluation (pp. 445-448). New York, NY:
Elsevier.
72. Haufroid. V., Thirion, F., Mertens, P., Buchet, J.P., Lison, D.
1997. Biological monitoring of workers exposed to low levels of 2-
butoxyethanol. Int. Arch. Occup. Environ. Health. 70: 232-236.
73. Bringmann, G., Kuhn, R. 1977. Limiting values for the damaging
action of water pollutants to bacteria (Pseudomonas putida) and
green algae (Scenedesmus quadricauda) in the cell multiplication
inhibition test. Z. Wasser Abwasser Forsch. 10(3/4): 87-98. (In
German)
74. Devillers, J., Chezeau, A., Thybaud, E., Poulsen, V., Procher,
J.-M., Graff, L., Vasseur, P., Mouchet, F., Ferrier, V., Quiniou, F.
2002. Ecotoxicity of ethylene glycol monobutyl ether and its
acetate. Toxicology Mechanisms and Methods, 12: 255-263.
75. Devillers, J., Chezeau, A., Thybaud, E., Poulsen, J.-M., Graff,
L., Vasseur, P., Chenon, P., Mouchet, F., Ferrier, V., Quiniou, F.
2002. Ecotoxicity of ethylene glycol monomethyl ether and its
acetate. Toxicology Mechanisms and Methods. 12: 241-254.
76. INERIS. 1999. D[eacute]termination de la toxicit[eacute]
chronique du 2-butoxyethanol vis-[agrave]-vis de l'algue d'eau douce
Pseudokirchneriella subcapitata, Ba746d-CGR21427. Verneuil-en-
Halatte, France, 14 december 1999, INERIS: 14. As cited in Ref. 77.
77. ECB (European Chemicals Bureau). 2006. European Union Risk
Assessment Report for 2-Butoxyethanol (EGBE). Vol. 68. European
Commission.
78. Bringmann, G., Kuhn, R. 1982. Results of the toxic action of
water pollutants on Daphnia magna in an improved standardized
procedure. Z. Wasser Abwasser Forsch. 15(1): 1-6. (In German)
79. Juhnke, I., Luedemann, D. 1978. Results of the study of 200
chemical compounds on acute fish toxicity using the Golden Orfe
test. Z. Wasser Abwasser Forsch. 11(5): 161-164. (In German)
80. Dow Chemical Co. 1979. Toxicity of Dowanol EB to freshwater
organisms (redactor: Bartlett), 31 August 1979. As cited in Ref. 77.
81. Dawson, G.W., Jennings, A.L., Drozdowski, D., Rider, E. 1975.
The acute toxicity of 47 industrial chemicals
[[Page 60825]]
to fresh and saltwater fishes. Journal of Hazardous Materials. 1:
303-318.
82. INERIS. 1999. D[eacute]termination de la toxicit[eacute]
aigu[euml] du 2-butoxyethanol vis-[agrave]-vis de Oncorhynchus
mykiss, unpublished, Ba746f-CGR21427. Verneuil-en-Halatte, France,
14 december 1999, INERIS: 10. As cited in Ref. 77.
83. Bridie, A.L., Wolff, C.J.M., Winter, M. 1979. The acute toxicity
of some petrochemicals to goldfish. Water Res. 13(7): 623-626.
84. Price, K.S., Waggy, G.T., Conway, R.A. 1974. Brine shrimp
bioassay and seawater BOD of petrochemicals. Journal WPCF. 46(1):
63-76.
85. Bringmann, G., Kuhn, R. 1978. Threshold Values of Substances
Harmful to Water for Blue Algae (Microcystis aeruginosa) and Green
Algae (Scenedesmus quadricauda) in Tests Measuring the Inhibition of
Cellular Propagation. Vom Wasser. 50:45 60 (in German) (English
Abstract), Tr 80 0201, Literature Research Company: 22 p.
86. Bringmann, G., Kuhn, R. 1978. Testing of Substances for Their
Toxicity Threshold: Model Organisms Microcystis (Diplocystis)
aeruginosa and Scenedesmus quadricauda. Mitt. Int. Ver. Theor.
Angew. Limnol. 21: 275 284.
87. Dill, DC, Milazzo, D.P. 1988. Dowanol PM Glycol Ether:
Evaluation of the toxicity to the green alga, Selenastrum
capricornutum Printz. Dow Chemical Company. EPA Document Control
Number 86-890001160. 18 pages.
88. INERIS. 1999. D[eacute]termination de la toxicit[eacute]
chronique du 2-butoxyethanol vis-[agrave]-vis de Daphnia magna,
Ba746a-CGR21427. Verneuil-en-Halatte, France, 15 december 1999,
INERIS: 13. As cited in Ref. 77.
89. INERIS. 2001. Essai poisson 21 jours, Danio rerio, unpublished
report, N[deg] 22685, 05.11.2001. As cited in Ref. 77.
List of Subjects in 40 CFR Part 372
Environmental protection, Community right-to-know, Reporting and
recordkeeping requirements, and Toxic chemicals.
Dated: September 24, 2015.
Arnold E. Layne,
Director, Office of Information Analysis and Access.
[FR Doc. 2015-25674 Filed 10-7-15; 8:45 am]
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