
[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: bushman.daniel@epa.gov, 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.
------------------------------------------------------------------------

    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 
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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]]

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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]
 BILLING CODE 6560-50-P


