80_FR_61013 80 FR 60818 - Ethylene Glycol Monobutyl Ether; Community Right-To-Know Toxic Chemical Release Reporting

80 FR 60818 - Ethylene Glycol Monobutyl Ether; Community Right-To-Know Toxic Chemical Release Reporting

ENVIRONMENTAL PROTECTION AGENCY

Federal Register Volume 80, Issue 195 (October 8, 2015)

Page Range60818-60825
FR Document2015-25674

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.

Federal Register, Volume 80 Issue 195 (Thursday, October 8, 2015)
[Federal Register Volume 80, Number 195 (Thursday, October 8, 2015)]
[Proposed Rules]
[Pages 60818-60825]
From the Federal Register Online  [www.thefederalregister.org]
[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.
------------------------------------------------------------------------

    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.thefederalregister.org/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]]

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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]
 BILLING CODE 6560-50-P



                                               60818                      Federal Register / Vol. 80, No. 195 / Thursday, October 8, 2015 / Proposed Rules

                                               ENVIRONMENTAL PROTECTION                                    of 1986 and section 6607 of the                       Pennsylvania Ave. NW., Washington,
                                               AGENCY                                                      Pollution Prevention Act (PPA) of 1990.               DC 20460; telephone number: 202–566–
                                                                                                           EPA has reviewed the available data on                0743; fax number: 202–566–0677; email:
                                               40 CFR Part 372                                             this chemical and has determined that                 bushman.daniel@epa.gov, for specific
                                                                                                           EGBE does not meet the deletion                       information on this notice. For general
                                               [EPA–HQ–TRI–2015–0352; FRL 9935–38–                         criterion of EPCRA section 313(d)(3).                 information on EPCRA section 313,
                                               OEI]                                                        Specifically, EPA is denying this                     contact the Emergency Planning and
                                                                                                           petition because EPA’s review of the                  Community Right-to-Know Hotline, toll
                                               Ethylene Glycol Monobutyl Ether;                            petition and available information                    free at (800) 424–9346 (select menu
                                               Community Right-To-Know Toxic                               resulted in the conclusion that EGBE                  option 3) or (703) 412–9810 in Virginia
                                               Chemical Release Reporting                                  meets the listing criterion of EPCRA                  and Alaska or toll free, TDD (800) 553–
                                               AGENCY: Environmental Protection                            section 313(d)(2)(B) due to its potential             7672, http://www.epa.gov/superfund/
                                               Agency (EPA).                                               to cause serious or irreversible chronic              contacts/infocenter/.
                                                                                                           health effects in humans, specifically,
                                               ACTION: Denial of petition.                                                                                       SUPPLEMENTARY INFORMATION:
                                                                                                           liver toxicity and concerns for
                                               SUMMARY:   Environmental Protection                         hematological effects.                                I. General Information
                                               Agency (EPA) is denying a petition to                       DATES: EPA denied this petition on
                                                                                                                                                                 A. Does this notice apply to me?
                                               remove ethylene glycol monobutyl ether                      September 24, 2015.
                                               (EGBE) from the category Certain Glycol                     FOR FURTHER INFORMATION CONTACT:                         You may be potentially affected by
                                               Ethers under the list of chemicals                          Daniel R. Bushman, Environmental                      this action if you manufacture, process,
                                               subject to reporting under section 313 of                   Analysis Division, Office of Information              or otherwise use EGBE. Potentially
                                               the Emergency Planning and                                  Analysis and Access (2842T),                          affected categories and entities may
                                               Community Right-to-Know Act (EPCRA)                         Environmental Protection Agency, 1200                 include, but are not limited to:

                                                         Category                                                              Examples of potentially 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                         www.regulations.gov or in hard copy at                chemicals annually. These facilities
                                               exhaustive, but rather provides a guide                     the OEI Docket, EPA/DC, EPA West,                     must also report pollution prevention
                                               for readers regarding entities likely to be                 Room 3334, 1301 Constitution Ave.                     and recycling data for such chemicals,
                                               affected by this action. Some of the                        NW., Washington, DC. This Docket                      pursuant to section 6607 of the PPA, 42
                                               entities listed in the table have                           Facility is open from 8:30 a.m. to 4:30               U.S.C. 13106. Congress established an
                                               exemptions and/or limitations regarding                     p.m., Monday through Friday, excluding                initial list of toxic chemicals that
                                               coverage, and other types of entities not                   legal holidays. The telephone number                  comprised more than 300 chemicals and
                                               listed in the table could also be affected.                 for the Public Reading Room is (202)                  20 chemical categories.
                                               To determine whether your facility                          566–1744, and the telephone number for
                                                                                                                                                                   EPCRA section 313(d) authorizes EPA
                                               would be affected by this action, you                       the OEI Docket is (202) 566–1752.
                                               should carefully examine the                                  2. Electronic Access. You may access                to add or delete chemicals from the list
                                               applicability criteria in part 372 subpart                  this Federal Register document                        and sets criteria for these actions.
                                               B of Title 40 of the Code of Federal                        electronically from the Government                    EPCRA section 313(d)(2) states that EPA
                                               Regulations. If you have questions                          Printing Office under the ‘‘Federal                   may add a chemical to the list if any of
                                               regarding the applicability of this action                  Register’’ listings at FDSys (http://                 the listing criteria in Section 313(d)(2)
                                               to a particular entity, consult the person                  www.gpo.gov/fdsys/browse/                             are met. Therefore, to add a chemical,
                                               listed in the preceding FOR FURTHER                         collection.action?collectionCode=FR).                 EPA must demonstrate that at least one
                                               INFORMATION CONTACT section.                                                                                      criterion is met, but need not determine
                                                                                                           II. Introduction
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                                                                                                                                                                 whether any other criterion is met.
                                               B. How can I get copies of this document                       Section 313 of EPCRA, 42 U.S.C.                    EPCRA section 313(d)(3) states that a
                                               and other related information?                              11023, requires certain facilities that               chemical may be deleted if the
                                                 1. Docket. EPA has established a                          manufacture, process, or otherwise use                Administrator determines there is not
                                               docket for this action under Docket ID                      listed toxic chemicals in amounts above               sufficient evidence to establish any of
                                               No. EPA–HQ–TRI–2015–0352. Publicly                          reporting threshold levels to report their            the criteria described in EPCRA section
                                               available docket materials are available                    environmental releases and other waste                313(d)(2)(A)–(C). The EPCRA section
                                               either electronically in                                    management quantities of such                         313(d)(2)(A)–(C) criteria are:


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                                                                     Federal Register / Vol. 80, No. 195 / Thursday, October 8, 2015 / Proposed Rules                                           60819

                                               • The chemical is known to cause or                     is not individually listed under EPCRA                Rettenmeier et al. (Ref. 16) that
                                                  can reasonably be anticipated to cause               section 313 but rather is reportable                  approximately two-thirds of the BAA
                                                  significant adverse acute human                      under the Certain Glycol Ethers                       formed in humans is conjugated with
                                                  health effects at concentration levels               category. The petitioner contends that                glutamine and glycine. These pathways,
                                                  that are reasonably likely to exist                  the available scientific data show that               however, have not been observed in the
                                                  beyond facility site boundaries as a                 EGBE has low potential hazard to                      rat.
                                                  result of continuous, or frequently                  human health and the environment.                        Several experimental studies have
                                                  recurring, releases.                                 Therefore, the petitioner believes that               measured the concentration of BAA in
                                               • The chemical is known to cause or                     under EPA’s policy for listing decisions              human serum and urine following
                                                  can reasonably be anticipated to cause               under EPCRA section 313, potential                    exposure to EGBE. For humans, the
                                                  in humans:                                           exposures should be considered. The                   elimination kinetics of EGBE and BAA
                                                  Æ Cancer or teratogenic effects, or                  petitioner believes that their analysis               appear to be independent of the route of
                                                  Æ serious or irreversible—                           shows that exposure levels are well                   exposure with an approximate half-life
                                                  D reproductive dysfunctions,                         below the concern levels for human                    of around one hour for EGBE and an
                                                  D neurological disorders,                            health and ecological effects.                        approximate half-life of BAA of 3–4
                                                  D heritable genetic mutations, or                                                                          hours (Refs. 17, 18, and 19).
                                                  D other chronic health effects.                      IV. What is EPA’s evaluation of the                      Several physiologically based
                                               • The chemical is known to cause or                     toxicity of EGBE?                                     pharmacokinetic models for EGBE have
                                                  can be reasonably anticipated to                        EPA’s evaluation of the toxicity of                been developed. Some older models
                                                  cause, because of:                                   EGBE included a review of the human                   have described the kinetics of EGBE for
                                                  Æ its toxicity,                                      health and ecological effects data. EPA’s             acute human exposure and exposure to
                                                  Æ its toxicity and persistence in the                Integrated Risk Information System                    rats via the ingestion, inhalation, and
                                                    environment, or                                    (IRIS) toxicological review of EBGE (Ref.             dermal routes (Refs. 17 and 20 based on
                                                  Æ its toxicity and tendency to                       2) was the primary source used to                     data from Refs. 13, 21, and 22). Newer
                                                    bioaccumulate in the environment,                  determine the human health effects of                 models, however, have extended upon
                                               a significant adverse effect on the                     EGBE. EPA also prepared an assessment                 the work of these previous models.
                                                  environment of sufficient seriousness,               of the chemistry, fate, and ecological                Corley et al. (Ref. 7) described the
                                                  in the judgment of the Administrator,                effects for EGBE (Ref. 3).                            kinetics of EGBE and BAA in both rats
                                                  to warrant reporting under this                                                                            and humans. These authors later
                                                  section.                                             A. What is EPA’s review of the human
                                                                                                                                                             validated the human dermal exposure
                                                  EPA often refers to the section                      health toxicity data for EGBE?
                                                                                                                                                             model (Ref. 8). Lee et al. (Ref. 23)
                                               313(d)(2)(A) criterion as the ‘‘acute                     EPA’s evaluation of the toxicity of                 modeled the kinetics of EGBE and BAA
                                               human health effects criterion;’’ the                   EGBE included a review (Ref. 4) of the                in mice and rats from a National
                                               section 313(d)(2)(B) criterion as the                   IRIS toxicological review of EGBE (Ref.               Toxicology Program (NTP) 2-year
                                               ‘‘chronic human health effects                          2). EPA also reviewed the findings of                 inhalation bioassay (based on data from
                                               criterion;’’ and the section 313(d)(2)(C)               studies published since the IRIS                      Dill et al. (Ref. 24)). Species, gender,
                                               criterion as the ‘‘environmental effects                toxicological review of EGBE, but found               age, and exposure concentration-
                                               criterion.’’                                            no data relevant to include in this                   dependent differences in the kinetics of
                                                  Under section 313(e)(1), any person                  evaluation. This Unit outlines the                    BAA were observed. Corley et al. (Ref.
                                               may petition EPA to add chemicals to or                 evidence of human health toxicity from                12) built on the Lee et al. (Ref. 23)
                                               delete chemicals from the list. EPA                     the 2010 IRIS toxicological review of                 model by replacing some model
                                               issued a statement of petition policy and               EGBE. Unit IV.B. below discusses the                  assumptions with experimental data
                                               guidance in the Federal Register of                     conclusions regarding EGBE’s potential                (Note: The Corley et al. (Ref. 12) model,
                                               February 4, 1987 (52 FR 3479) to                        human health toxicity.                                along with the Lee et al. (Ref. 23) rat and
                                               provide guidance regarding the                            1. Toxicokinetics. In humans, EGBE is               mouse model and Corley et al. (Ref. 8)
                                               recommended content and format for                      absorbed and rapidly distributed                      human model were used by EPA to
                                               submitting petitions. On May 23, 1991                   following inhalation, ingestion, or                   calculate internal doses of EGBE in the
                                               (56 FR 23703), EPA issued guidance                      dermal exposure (Refs. 5, 6, 7, and 8).               2010 IRIS toxicological review of EGBE
                                               regarding the recommended content of                    Several reviews have described the                    (Ref. 2)).
                                               petitions to delete individual members                  metabolism of EGBE in detail (Refs. 9,                   2. Effects of Acute and Short-Term
                                               of the section 313 metal compounds                      10, and 11). The principal products                   Exposure. Hematologic and other effects
                                               categories. EPA published in the                        from EGBE metabolism are butoxyacetic                 have been observed in several acute and
                                               Federal Register of November 30, 1994                   acid (BAA) (rats and humans) and the                  short-term oral studies of EGBE in rats
                                               (59 FR 61432) a statement clarifying its                glutamine or glycine conjugate of BAA                 and mice (Refs. 15, 25, 26, 27, 28, 29,
                                               interpretation of the section 313(d)(2)                 (humans). BAA is excreted in the urine                30, 31, 32, 33, and 34). Varying degrees
                                               and (d)(3) criteria for modifying the                   of both rats and humans, which suggests               of hematotoxicity have also been
                                               section 313 list of toxic chemicals.                    that the creation of BAA through the                  observed in rats and rabbits following
                                                                                                       formation of butoxyacetaldehyde by                    dermal application of EGBE (Refs. 14
                                               III. What is the description of the                     alcohol dehydrogenase is applicable to                and 35). Guinea pigs, however, have not
                                               petition?                                               rats and humans (Refs. 8, 12, and 13).                demonstrated sensitivity to the
                                                  On January 23, 2015, EPA received a                  The other proposed metabolic                          hematologic effects of EGBE in acute
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                                               petition from American Chemistry                        pathways, however, may only be                        studies (Refs. 36 and 37). EGBE has also
                                               Council (ACC) Ethylene Glycol Ethers                    applicable to rats since the metabolites              been found to be an ocular irritant when
                                               Panel requesting EPA to delete EGBE                     of these pathways (i.e., ethylene glycol,             instilled in rabbits (Refs. 38 and 39).
                                               (Chemical Abstracts Service Registry                    EGBE glucuronide, and EGBE sulfate)                      A few in vitro studies have
                                               Number (CASRN) 111–76–2) from the                       have been observed in the urine of rats               investigated EGBE’s potential hemolytic
                                               list of chemicals subject to reporting                  (Refs. 14 and 15), but not in humans                  effects in human red blood cells after
                                               under EPCRA section 313 and PPA                         (Ref. 8). In addition, Corley et al. (Ref.            acute exposures. Bartnik et al. (Ref. 14)
                                               section 6607 (Reference (Ref. 1)). EGBE                 8) confirmed the finding from                         reported no hemolysis of human red


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                                               60820                 Federal Register / Vol. 80, No. 195 / Thursday, October 8, 2015 / Proposed Rules

                                               blood cells exposed for three hours to                  developmental toxicant at moderately                  doses in female mice. Body weight
                                               BAA levels up to 15 millimolar (mM).                    low to low doses.                                     reductions followed decreased water
                                               Hemolysis was observed in rat red blood                    5. Neurotoxicity. There is no evidence             consumption. No histopathologic
                                               cells, however, at BAA levels as low as                 of neurotoxicity in any animal studies of             changes were noted at any dose level,
                                               1.25 mM. Udden (Ref. 40) incubated                      EGBE. One case study patient                          however, relative kidney weights
                                               human red blood cells with up to 2.0                    demonstrated neurologic deficits after                showed a statistically significant
                                               mM BBA for four hours, and the authors                  ingesting a product with a high dose of               increase at 750 and 1,500 ppm in the
                                               observed none of the morphological                      EGBE and other chemicals (Ref. 47).                   absence of reduction in body weight
                                               changes observed in rat red blood cells                 Given the general limitations of case                 gain. The NTP (Ref. 66) identified a
                                               at the same concentration. Udden (Ref.                  studies and the presence of other                     LOAEL for mice of 3,000 ppm
                                               41) reported a significant change in                    chemicals, however, EPA cannot draw                   (approximately, 553–676 mg/kg/day
                                               human red blood cell deformability at                   conclusions about EGBE’s potential                    calculated using water consumption
                                               exposure to 7.5 and 10 mM BAA for 4                     neurotoxicity from this particular study.             rates and body weights measured during
                                               hours, whereas deformability in rat red                    6. Other Subchronic and Chronic                    the last week of exposure and, therefore,
                                               blood cells was significantly increased                 Toxicity. Hematologic effects and liver               slightly different from those reported by
                                               at 0.05 mM BAA. Mean cellular volume                    toxicity have been observed at low                    the study authors (Ref. 2)) based on
                                               in human blood samples was                              doses of EGBE in several animal studies.              reduced body weight and body weight
                                               significantly increased at 10 mM BAA                       The NTP (Ref. 66) conducted a 13-                  gain.
                                               while mean cellular volume in rats was                  week study in F344 rats and B6C3F1                       Dodd et al. (Ref. 62) conducted a 90-
                                               significantly increased at 0.05 mM BAA.                 mice in which groups of 10 animals/                   day subchronic inhalation study using
                                                  There are a number of case reports of                gender/species received EGBE in                       F344 rats (16/gender/group) exposed to
                                               acute ingestion of EGBE with little or no               drinking water at doses of 0, 750, 1,500,             EGBE for 6 hours/day, 5 days/week at
                                               hematologic effects observed (Refs. 42,                 3,000, 4,500, and 6,000 ppm. The                      concentrations of 0, 5, 25, and 77 ppm.
                                               43, 44, 45, 46, 47, 48, and 49). Some                   corresponding doses based on measured                 After 6 weeks, the 77 ppm female rats
                                               other observed effects were likely not                  drinking water consumption were: 0, 69,               had statistically significant decreases in
                                               directly related to hemolysis; however,                 129, 281, 367, or 452 milligrams/                     red blood cell counts (13%) and
                                               the cause of the effects cannot be                      kilogram/day (mg/kg/day) in male rats;                hemoglobin concentrations,
                                               explained based on the limited data                     0, 82, 151, 304, 363, or 470 mg/kg/day                accompanied by an 11% increase in
                                               available. Also, hemodialysis was                       in female rats; 0, 118, 223, 553, 676, or             mean corpuscular hemoglobin. Similar
                                               employed to remove un-metabolized                       694 mg/kg/day in male mice; and 0, 185,               results were observed in males.
                                               EGBE in many of the cases.                              370, 676, 861, or 1,306 mg/kg/day in                  However, many of these effects had
                                                  One experimental study in humans                     female mice.                                          lessened by the end of the study. The
                                               (Ref. 50), observed no effects on red                      Indications of mild to moderate                    authors reported a LOAEL of 77 ppm
                                               blood cell fragility after exposure of two              anemia were observed in both genders.                 based on decreases in red blood cell
                                               males and one female to up to 195 part                  Statistically significant hematologic                 count and hemoglobin concentrations,
                                               per million (ppm) EGBE for 8 hours.                     effects in female rats included reduced               accompanied by an increase in mean
                                                  3. Carcinogenicity and Mutagenicity.                 red blood cell counts and hemoglobin                  corpuscular hemoglobin in both
                                               Under the Guidelines for Carcinogen                     concentrations at ≥750 ppm and                        genders.
                                               Risk Assessment (Ref. 51), there is                     increased reticulocytes, decreased                       The NTP (Ref. 52) conducted a
                                               suggestive evidence of EGBE’s                           platelets, and increased bone marrow                  subchronic inhalation study in F344 rats
                                               carcinogenic potential based on a 2-year                cellularity at 3,000 ppm. Liver effects               and B6C3F1 mice (10/gender). Rats and
                                               NTP bioassay in mice and rats (Ref. 52).                including cytoplasmic alterations,                    mice were exposed to EGBE
                                               EGBE has been tested for its potential                  hepatocellular degeneration, and                      concentrations of 0, 31, 62.5, 125, 250,
                                               for genotoxicity both in vitro and in                   pigmentation were reported in the mid-                and 500 ppm (0, 150, 302, 604, 1,208,
                                               vivo, and the available data do not                     and high-dose groups (≥1,500 ppm for                  and 2,416 milligrams/cubic meter (mg/
                                               demonstrate that EGBE is mutagenic or                   males and females; statistics not                     m3)) 6 hours/day, 5 days/week for 14
                                               clastogenic (Refs. 53, 54, 55, 56, 57, and              reported). Additionally, cytoplasmic                  weeks. The NTP (Ref. 52) identified a
                                               58).                                                    alterations of liver hepatocytes were                 LOAEL of 31 ppm in female rats based
                                                  4. Reproductive and Developmental                    observed in the lowest-dose groups (750               on decreases in hematocrit, hemoglobin,
                                               Toxicity. The reproductive and                          ppm for males and females). The lack of               and red blood cell count and a LOAEL
                                               developmental toxicity of EGBE has                      cytoplasmic granularity of the                        of 62.5 ppm in male rats based on a
                                               been investigated in a number of oral                   hepatocytes indicates that this response              decrease in red blood cell count.
                                               and inhalation studies in rats, mice, and               was not due to enzyme induction (Ref.                 Histopathologic effects were observed in
                                               rabbits. In a two-generation                            71). The NTP (Ref. 66) identified a                   male and female rats. Effects reported in
                                               reproductive toxicity study, fertility was              lowest-observed-adverse-effect level                  female rats included liver necrosis at
                                               reduced in mice at very high maternally                 (LOAEL) for rats of 750 ppm                           250 ppm and centrilobular degeneration
                                               toxic doses (≤1,000 milligrams/kilogram                 (approximately 58.6 mg/kg/day                         and renal tubular degeneration at 500
                                               (mg/kg)) (Ref. 59), but no other                        calculated using water consumption                    ppm. Other effects reported in both
                                               significant reproductive effects were                   rates and body weights measured during                genders included: Excessive splenic
                                               reported in any study (Refs. 26, 52, 60,                the last week of exposure and, therefore,             congestion in the form of
                                               61, 62, 63, 64, 65, and 66). Maternal                   slightly different from those reported by             extramedullary hematopoiesis (at 250
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                                               toxicity related to the hematologic                     the study authors (Ref. 2)) based on                  ppm in male rats and 125 ppm in female
                                               effects of EGBE and relatively minor                    decreased red blood cell count and                    rats), hemosiderin accumulation in
                                               developmental effects have been                         hemoglobin in female rats. A NOAEL                    Kupffer cells (at 125 ppm in male rats
                                               reported in developmental studies (Refs.                was not identified.                                   and 62.5 ppm in female rats),
                                               67, 68, 69, and 70). No teratogenic                        A reduction in body weight gain at                 intracytoplasmic hemoglobin (at 125
                                               effects were noted in any of the studies.               ≥3,000 ppm was observed in male and                   ppm in male rats and 31 ppm in female
                                               As such, EGBE is not reasonably                         female mice. An increase in relative                  rats), hemosiderin deposition (at 125
                                               anticipated to be a reproductive or                     kidney weight was also observed at all                ppm in male rats and 62.5 ppm in


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                                                                     Federal Register / Vol. 80, No. 195 / Thursday, October 8, 2015 / Proposed Rules                                          60821

                                               female rats), and bone marrow                           IRIS toxicological review of EGBE                        1. Acute toxicity. Toxicity threshold
                                               hyperplasia (at 250 ppm in male rats                    employed an interspecies uncertainty                  values (duration not specified) of 900
                                               and 62.5 ppm in female rats). The                       factor of 1 to derive the reference values            milligrams/liter (mg/L) and 72-hour
                                               authors identified a LOAEL of 62.5 ppm                  for EGBE in part because there was not                EC50 values (i.e., the concentration that
                                               for mice based on histopathological                     a preponderance of toxicodynamic data                 is effective in producing a sublethal
                                               changes in the forestomach (including:                  in both animals and humans describing                 response in 50% of test organisms) of
                                               Necrosis, ulceration, inflammation, and                 why humans are less sensitive than rats               911 and 1,840 mg/L for biomass and
                                               epithelial hyperplasia) in both males                   to the hematologic effects in question                growth rate, respectively, have been
                                               and females. Signs consistent with the                  (Ref. 2). Also, EPA calculated a human                reported for green algae (Refs. 73, 74,
                                               hemolytic effects of EGBE (including:                   equivalent concentration LOAEL                        and 75). The corresponding 72-hour No-
                                               Decreased red blood cell counts,                        (LOAELHEC) for hematologic effects of                 Observed-Effect-Concentration (NOEC)
                                               increased reticulocyte counts, and                      271 mg/m3 (approximately 77 mg/kg/                    values for biomass and growth rate were
                                               increased mean corpuscular volume)                      day, assuming constant exposure, an                   88 and 286 mg/L (Ref. 76). For water
                                               were also observed at 250 and 500 ppm                   inhalation rate of 20 cubic meters/day                fleas (Daphnia magna), 24- or 48-hour
                                               in male and female mice.                                (m3/day), and a 70 kg human) using                    EC50 values ranged from 835 to 1,815
                                                  The NTP (Ref. 52) also completed a 2-                pharmacokinetic model estimates (Refs.                mg/L (Refs. 77 and 78). A 48-hour EC50
                                               year inhalation study on EGBE in both                   7 and 8) of the human internal dose                   value of 164 mg/L in rotifers
                                               F344 rats and B6C3F1 mice. In this                      equivalent of the toxic metabolite BAA                (reproduction) has also been reported
                                               study, animals were exposed to EGBE 6                   to that estimated for female rats exposed             (Refs. 74 and 75).
                                               hours/day, 5 days/week at                               to 31 ppm EGBE in the NTP (Ref. 52)
                                               concentrations of 0, 31, 62.5, and 125                  study (Ref. 2). In its assessment of                     Acute toxicity values for freshwater
                                               ppm (0, 150, 302, and 604 mg/m3) for                    EGBE, the European Union carried out                  fish ranged from an LC50 (i.e., the
                                               groups of 50 F344 rats and 0, 62.5, 125,                a slightly different calculation based on             concentration that is lethal to 50% of
                                               and 250 ppm (0, 302, 604, and 1,208                     the same underlying data and reported                 test organisms) of 1,395 mg/L for the
                                               mg/m3) for groups of 50 B6C3F1 mice.                    a similar, but slightly higher, human                 golden orfe (Leuciscus idus) (duration
                                               The authors identified a LOAEL of 31                    equivalent LOAEL of 474 mg/m3                         not specified) (Ref. 79) to a 96-hour LC50
                                               ppm in rats based on decreases in                       (approximately 135 mg/kg/day) (Ref.                   of 2,137 mg/L for the fathead minnow
                                               hematocrit, hemoglobin, and red blood                   11).                                                  (Pimephales promelas) (Ref. 80). A 96-
                                               cell count in female rats in a satellite                   Additionally, multiple animal studies              hour LC50 value of 1,490 mg/L was
                                               group observed at 3 and 6 months. The                   by the NTP reported liver toxicity (e.g.,             available for bluegill sunfish (Ref. 81)
                                               authors identified 62.5 ppm as the                      cytoplasmic alterations of liver                      and 96-hour LC50 values for rainbow
                                               LOAEL for mice based on hemosiderin                     hepatocytes at 750 ppm (approximately                 trout were 1,474 and 1,700 mg/L (Refs.
                                               deposition.                                             69 mg/kg/day) in male rats and 750 ppm                74, 75, and 82). An LC50 value (duration
                                                  One long-term occupational study of                  (82 mg/kg/day) in female rats (Ref. 66)               not specified) of 1,575 mg/L was also
                                               EGBE was identified in the literature.                  and liver necrosis at 250 ppm                         available for golden orfe (Leuciscus
                                               Haufroid et al. (Ref. 72) reported a small              (approximately 243 mg/kg/day) in                      idus) (Ref. 79) and a 24-hour LC50 value
                                               decrease in hematocrit and increase in                  female rats (Ref. 52)) to which humans                of 1,700 mg/L was available for goldfish
                                               mean corpuscular hemoglobin in a cross                  do not demonstrate decreased                          (Carassius auratus) (Ref. 83).
                                               sectional study of 31 workers exposed to                sensitivity. These findings provide                      A study of the invertebrate Artemia
                                               an average concentration of 0.6 ppm                     further evidence of EGBE’s potential                  salina (brine shrimp) reported a 24-hour
                                               EGBE over 1 to 6 years. The biological                  toxicity to humans at moderately low to               LC50 value of 1,000 mg/L (Ref. 84). Also,
                                               significance of these findings, however,                low doses.                                            an embryo-larval test in which Japanese
                                               is unclear as they were within normal                      Therefore, the available evidence is
                                                                                                                                                             oyster eggs (Crassostrea gigas) were
                                               clinical ranges and no other measured                   sufficient to conclude that EGBE can be
                                                                                                                                                             incubated with the test material for 24
                                               parameters were affected by EGBE                        reasonably anticipated to demonstrate
                                                                                                                                                             hours and then examined for
                                               exposure.                                               moderately high to high chronic toxicity
                                                                                                                                                             abnormalities indicated an identical 24-
                                                                                                       in humans based on the EPCRA Section
                                               B. What are EPA’s conclusions                                                                                 hour Lowest-Observed-Effect-
                                                                                                       313 listing criteria (59 FR 61432,
                                               regarding the human hazard potential                                                                          Concentration (LOEC) of 1,000 mg/L
                                                                                                       November 30, 1994).
                                               of EGBE?                                                                                                      (Ref. 74). A study of an estuarine/marine
                                                 There is evidence to indicate that the                C. What is EPA’s review of the                        fish silverside (Menidia beryllina)
                                               human red blood cell response to EGBE                   ecological toxicity of EGBE?                          reported a 96-hour LC50 value of 1,250
                                               exposure is less than that of rodents,                     Based on a review of the available                 mg/L (Ref. 81).
                                               however, this conclusion is based on a                  aquatic ecological toxicity data, EGBE                   2. Chronic toxicity. Values for chronic
                                               relatively small number of in vitro and                 does not appear to present a significant              toxicity in aquatic plants ranged from an
                                               short-term human exposure studies with                  concern for adverse effects on the                    8-day LOEC (inhibition of cell division)
                                               supporting evidence from                                environment. Experimentally measured                  of 35 mg/L for the cyanobacteria
                                               pharmacokinetic models (Refs. 7, 8, 14,                 effects occurred at relatively high                   Microcystis aeruginosa (Refs. 85 and 86)
                                               40, 41, and 50). Little is known of the                 concentrations indicating low toxicity                to greater than 1,000 mg/L for a 7-day
                                               long-term or repeated exposure                          (Ref. 3). Such high concentrations are                EC50 (growth rate) for the green alga
                                               responses in humans to EGBE.                            not expected to be observed under                     Selenastrum capricornutum (Ref. 87).
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                                                 In 2010, EPA concluded in the IRIS                    typical environmental conditions. Table               Experimental data for the freshwater
                                               toxicological review of EGBE that                       1 presents some of the available toxicity             invertebrate Daphnia magna include
                                               human red blood cells do appear                         data for EGBE, the complete listing of                values that ranged from 100 mg/L for a
                                               capable of responding similarly to the                  the available toxicity data and more                  21-day NOEC (reproduction) (Refs. 74,
                                               causative EGBE metabolites, albeit at                   details about the studies can be found                75, and 77) to an EC50 of 297 mg/L
                                               much higher exposures (Ref. 2). The                     in the ecological assessment (Ref. 3).                (endpoint not reported) (Ref. 88).




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                                               60822                    Federal Register / Vol. 80, No. 195 / Thursday, October 8, 2015 / Proposed Rules

                                                      TABLE 1—RANGE OF EXPERIMENTAL ECOLOGICAL TOXICITY VALUES FOR EGBE ON SELECTED TARGET SPECIES
                                                                                                                                                                   Experiment                 Value
                                                                            Species                                    Duration and test endpoint                                                                  Reference
                                                                                                                                                                     type a                  (mg/L)

                                                                                                                           Acute aquatic toxicity

                                               Algae:
                                                   Green algae (Pseudokirchneriella subcapitata) ......                72-hour EC50 (growth) .......              S, M .............             1,840      (Refs. 74 and 75).
                                                   Green algae (Pseudokirchneriella subcapitata) ......                72-hour NOEC (biomass) ..                  S, M ............                 88      (Ref. 82).
                                               Freshwater invertebrate:
                                                   Water flea (Daphnia magna) ...................................      48-hour EC50 .....................         S, U, O ........               1,815      (Ref. 78).
                                                   Rotifer (Brachionus calyciflorus) .............................     48-hour EC50 (reproduc-                    S, M .............               164      (Refs. 74 and 75).
                                                                                                                         tion).
                                               Freshwater fish:
                                                   Golden orfe (Leuciscus idus) ..................................     LC50 ...................................   NS ...............             1,395      (Ref. 79).
                                                   Fathead minnow (Pimephales promelas) ...............                96-hour LC50 ......................        S, O .............             2,137      (Ref. 80).
                                               Estuarine/marine invertebrate:
                                                   Brine shrimp (Artemia salina) ..................................    24-hour LC50 ......................        S, U, C ........               1,000      (Ref. 84).
                                                   Japanese oyster eggs (Crassostrea gigas) ............               24-hr LOEC                                 S ..................           1,000      (Refs. 74 and 75).
                                                                                                                         (embryotoxicity).
                                               Estuarine/marine fish:
                                                   Silverside (Menidia beryllina) ..................................   96-hour LC50 ......................        S, U .............             1,250      (Ref. 81).

                                                                                                                          Chronic aquatic toxicity

                                               Algae:
                                                   Blue-green algae (Microcystis aeruginosa) .............             8-day LOEC (cell mul-                      S, U .............                  35    (Refs. 85 and 86).
                                                                                                                         tiplication inhibition).
                                                   Green algae (Selenastrum capricornutum) .............               7-day EC50 (growth rate) ...               S, U .............            >1,000      (Ref. 87).
                                               Freshwater invertebrate:
                                                   Water flea (Daphnia magna) ...................................      21-day NOEC (reproduc-                     R, M ............                   100   (Refs. 74 and 75).
                                                                                                                         tion).
                                                   Water flea (Daphnia magna) ...................................      21-day NOEC ....................           R, M ............                   100   (Ref. 88).
                                                   Water flea (Daphnia magna) ...................................      21-day EC50 .......................        R, M ............                   297   (Ref. 88).
                                               Freshwater fish:
                                                   Zebrafish (Brachydanio rerio) ..................................    21-day NOEC (mortality) ...                NS ...............              >100      (Ref. 89).
                                                  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                             Because EPA believes that EGBE has                                  physically located in the docket, please
                                               denial?                                                      moderately high to high chronic                                       consult the person listed in the above
                                                                                                            toxicity, EPA does not believe that an                                FOR FURTHER INFORMATION CONTACT
                                                  EPA is denying the petition to delete                     exposure assessment is appropriate for                                section.
                                               EGBE from the Certain Glycol Ethers                          determining whether EGBE meets the                                    1. American Chemistry Council. 2014.
                                               category which is subject to reporting                       criteria of EPCRA section 313(d)(2)(B).                                   Petition of the American Chemistry
                                               under EPCRA section 313. This denial                         This determination is consistent with                                     Council’s Ethylene Glycol Ethers Panel
                                               is based on EPA’s conclusion that EGBE                       EPA’s published statement clarifying its                                  To Remove Ethylene Glycol Monobutyl
                                               can reasonably be anticipated to cause                       interpretation of the section 313(d)(2)                                   Ether From the Toxics Release Inventory
                                               serious or irreversible chronic health                       and (d)(3) criteria for modifying the                                     Under Section 313 Of The Emergency
                                                                                                            section 313 list of toxic chemicals (59                                   Planning and Community Right-To-
                                               effects in humans, specifically, liver                                                                                                 Know Act of 1986. December 29, 2014.
                                               toxicity and concerns for hematological                      FR 61432, November 30, 1994).                                         2. U.S. EPA. 2010. Toxicological review of
                                               effects. While EPA acknowledges that                         VI. References                                                            Ethylene Glycol Monobutyl Ether
                                               there is evidence to indicate that                                                                                                     (CASRN 111–76–2) in support of
                                                                                                              EPA has established an official public                                  summary information on the Integrated
                                               humans are less sensitive than rodents
                                                                                                            docket for this action under Docket ID                                    Risk Information System (IRIS). U.S.
                                               to the hematological effects associated
                                                                                                            No. EPA–HQ–TRI–2015–0352. The                                             Environmental Protection Agency.
                                               with acute or short-term exposure to                         public docket includes information                                        Washington, DC. http://www.epa.gov/
                                               EGBE, little is known of the long-term                       considered by EPA in developing this                                      iris/toxreviews/0500tr.pdf.
                                               or repeated exposure responses in                            action, including the documents listed                                3. U.S. EPA. 2009. Technical Review of
                                               humans to EGBE. Thus, some concern                                                                                                     Ethylene Glycol Monobutyl Ether
                                                                                                            below, which are electronically or                                        (EGBE): Chemistry, Environmental Fate
                                               remains over the potential for                               physically located in the docket. In                                      and Ecological Toxicity CAS Registry
                                               hematological effects following a                            addition, interested parties should                                       Number 111–76–2. Office of
                                               lifetime of exposure to EGBE. Unlike the                     consult documents that are referenced                                     Environmental Information. September
                                               hematological effects of EGBE, there is
Lhorne on DSK5TPTVN1PROD with PROPOSALS




                                                                                                            in the documents that EPA has placed                                      9, 2009.
                                               no evidence of humans’ decreased                             in the docket, regardless of whether                                  4. U.S. EPA. 2015. Memorandum from
                                               sensitivity to the reported liver effects                    these referenced documents are                                            Jocelyn Hospital, Toxicologist,
                                               relative to rodents. Therefore, EPA has                                                                                                Environmental Analysis Division to
                                                                                                            electronically or physically located in
                                                                                                                                                                                      Megan Carroll, Acting Division Director
                                               concluded that EGBE meets the EPCRA                          the docket. For assistance in locating                                    of the Environmental Analysis Division.
                                               section 313(d)(2)(B) listing criteria based                  documents that are referenced in                                          July 24, 2015. Subject: Review of the
                                               on the available human health toxicity                       documents that EPA has placed in the                                      Data in the 2010 Integrated Risk
                                               data.                                                        docket, but that are not electronically or                                Information System (IRIS) Toxicological



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                                                                     Federal Register / Vol. 80, No. 195 / Thursday, October 8, 2015 / Proposed Rules                                              60823

                                                    Review of Ethylene Glycol Monobutyl                     butoxyethanol. Int. Arch. Occup.                      Nyska, M., Redlich, M., Tsipis, F.,
                                                    Ether (EGBE).                                           Environ. Health. 65: S151–S153.                       Yedgar, S. 2003. 2-Butoxyethanol
                                               5. Kumagai, S., Oda H., Matsunaga I., Kosaka            17. Johanson, G. 1986. Physiologically based               enhances the adherence of red blood
                                                    H., Akasaka S. 1999. Uptake of 10 polar                 pharmacokinetic modeling of inhaled 2-                cells. Arch. Toxicol. 77: 465–469.
                                                    organic solvents during short-term                      butoxyethanol in man. Toxicol. Lett. 34:         30. Shabat, S., Nyska, A., Long, P.H.,
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                                               6. Johanson G., Boman A. 1991. Percutaneous             18. Johanson, G., Johnsson, S. 1991. Gas                   Levin-Harrus, T., Peddada, S., Redlich,
                                                    absorption of 2-butoxyethanol vapour in                 chromatographic determination of                      M., Yedgar, S., Nyska, M. 2004.
                                                    human subjects. Occup. Environ. Med.                    butoxyacetic acid in human blood after                Osteonecrosis in a chemically induced
                                                    48: 788–792.                                            exposure to 2-butoxyethanol. Arch.                    rat model of human hemolytic disorders
                                               7. Corley R.A., Bormett G.A., Ghanayem B.I.                  Toxicol. 65: 433–435.                                 associated with thrombosis—a new
                                                    1994. Physiologically-based                        19. Johanson, G., Boman, A., Dynesius, B.                  model for avascular necrosis of bone.
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                                                    and its major metabolite 2-butoxyacetic                 butoxyethanol in man. Scand. J. Work             31. Redlich, M., Maly, A., Aframian, D.,
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                                               8. Corley R.A., Markham D.A., Banks C.,                      Birnbaum, L.S., Henderson, R.F. 1993.                 Histopathologic changes in dental and
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                                                    humans. Fundam. Appl. Toxicol. 39:                 21. Sabourin, P.J., Medinsky, M.A.,                        Miller, R.A., Thrall, B.D. 1999. Short-
                                                    120–130.                                                Birnbaum, L.S., Griffith, W.C.,                       term studies to evaluate the dosimetry
                                               9. Commonwealth of Australia. 1996.                          Henderson, R.F. 1992. Effect of exposure              and modes of action of EGBE in B6C3F1
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                                                    6-2-butoxyethanol in cleaning products.            22. Sabourin, P.J., Medinsky, M.A.,                   33. Poet, T.S., Soelberg, J.J., Weitz, K.K.,
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                                                                                                            methoxyethanol, ethoxyethanol, and                    butoxyethanol in the mouse with an
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                                               60824                 Federal Register / Vol. 80, No. 195 / Thursday, October 8, 2015 / Proposed Rules

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                                                    butoxyethanol: Case report and literature               Reel, J.R., Lawton, AD., Lamb IV, J.C.                drug safety evaluation (pp. 445–448).
                                                    review. J. Toxicol. Clin. Toxicol. 41: 57–              1990. Assessment of ethylene glycol                   New York, NY: Elsevier.
                                                    62.                                                     monobutyl and monophenyl ether                   72. Haufroid. V., Thirion, F., Mertens, P.,
                                               46. Rambourg-Schepens, M.O., Buffet, M.,                     reproductive toxicity using a continuous              Buchet, J.P., Lison, D. 1997. Biological
                                                    Bertault. R., Jaussaud, M., Journe, B.,                 breeding protocol in Swiss CD–1 Mice.                 monitoring of workers exposed to low
                                                    Fay, R., Lamiable, D. 1988. Severe                      Fundam. Appl. Toxicol. 15: 683–696.                   levels of 2-butoxyethanol. Int. Arch.
                                                    ethylene glycol butyl ether poisoning.             60. Nagano, K., Nakayama, E., Koyano, M.,                  Occup. Environ. Health. 70: 232–236.
                                                    Kinetics and metabolic pattern. Hum                     Oobayashi, H., Adachi, H., Yamada, T.            73. Bringmann, G., Kuhn, R. 1977. Limiting
                                                    Toxicol, 7: 187–189.                                    1979. Testicular atrophy of mice induced              values for the damaging action of water
                                               47. Burkhart, K.K., Donovan, J.W. 1998.                      by ethylene glycol mono alkyl ethers                  pollutants to bacteria (Pseudomonas
                                                    Hemodialysis following butoxyethanol                    (author’s translation). Sangyo Igaku/Jap.             putida) and green algae (Scenedesmus
                                                    ingestion. Clin. Toxicol. 36: 723–725.                  J. Ind. Health. 21: 29–35.                            quadricauda) in the cell multiplication
                                               48. Osterhoudt, K.C. 2002. Fomepizole                   61. Nagano, K., Nakayama, E., Oobayashi, H.,
                                                                                                                                                                  inhibition test. Z. Wasser Abwasser
                                                    therapy for pediatric butoxyethanol                     Nishizawa, T., Okuda, H., Yamazaki, K.
                                                                                                                                                                  Forsch. 10(3/4): 87–98. (In German)
                                                    intoxication. J. Toxicol. Clin. Toxicol. 40:            1984. Experimental studies on toxicity of
                                                                                                                                                             74. Devillers, J., Chezeau, A., Thybaud, E.,
                                                    929–930.                                                ethylene glycol alkyl ethers in Japan.
                                                                                                                                                                  Poulsen, V., Procher, J.-M., Graff, L.,
                                               49. Dean, B.S., Krenzelok, E.P. 1991. Critical               Environ. Health. Perspect. 57: 75–84.
                                                                                                                                                                  Vasseur, P., Mouchet, F., Ferrier, V.,
                                                    evaluation of pediatric ethylene glycol            62. Dodd, D.E., Snellings, W.M., Maronpot,
                                                                                                                                                                  Quiniou, F. 2002. Ecotoxicity of ethylene
                                                    monobutyl ether poisonings. Vet. Hum.                   R.R., Ballantyne, B. 1983. Ethylene
                                                                                                            glycol monobutyl ether: Acute, 9-day,                 glycol monobutyl ether and its acetate.
                                                    Toxicol. 33: 362.
                                               50. Carpenter, C.P., Pozzani, U.C., Weil, C.S.,              and 90-day vapor inhalation studies in                Toxicology Mechanisms and Methods,
                                                    Nair III, J.H., Keck, G.A., Smyth Jr., H.F.             Fischer 344 rats. Toxicol. Appl.                      12: 255–263.
                                                    1956. The toxicity of butyl cellosolve                  Pharmacol. 68: 405–414.                          75. Devillers, J., Chezeau, A., Thybaud, E.,
                                                    solvent. AMA Arch. Ind. Health. 14:                63. Doe, J.E. 1984. Further studies on the                 Poulsen, J.-M., Graff, L., Vasseur, P.,
                                                    114–131.                                                toxicology of the glycol ethers with                  Chenon, P., Mouchet, F., Ferrier, V.,
                                               51. U.S. EPA. 2005. Guidelines for                           emphasis on rapid screening and hazard                Quiniou, F. 2002. Ecotoxicity of ethylene
                                                    carcinogen risk assessment, Final Report.               assessment. Environ. Health Perspect.                 glycol monomethyl ether and its acetate.
                                                    Risk Assessment Forum, U.S.                             57: 199–206.                                          Toxicology Mechanisms and Methods.
                                                    Environmental Protection Agency.                   64. Foster, P.M., Lloyd, S.C., Blackburn, D.M.             12: 241–254.
                                                    Washington, DC. EPA/630/P–03/001F.                      1987. Comparison of the in vivo and in           76. INERIS. 1999. Détermination de la
                                                    http://cfpub.epa.gov/ncea/cfm/                          vitro testicular effects produced by                  toxicité chronique du 2-butoxyethanol
                                                    recordisplay.cfm?deid=116283.                           methoxy-, ethoxy- and N-butoxy acetic                 vis-à-vis de l’algue d’eau douce
                                               52. NTP. 2000. NTP technical report on the                   acids in the rat. Toxicology. 43: 17–30.              Pseudokirchneriella subcapitata,
                                                    toxicology and carcinogenesis studies of           65. Exon, J.H., Mather, G.G., Bussiere, J.L.,              Ba746d-CGR21427. Verneuil-en-Halatte,
                                                    2 butoxyethanol (CAS No. 111–76–2) in                   Olson, D.P., Talcott, P.A. 31991. Effects             France, 14 december 1999, INERIS: 14.
                                                    F344/N rats and B6C3F1 mice                             of subchronic exposure of rats to 2-                  As cited in Ref. 77.
                                                    (inhalation studies). National Toxicology               methoxyethanol or 2-butoxyethanol:               77. ECB (European Chemicals Bureau). 2006.
                                                    Program. Research Triangle Park, NC.                    Thymic atrophy and immunotoxicity.                    European Union Risk Assessment Report
                                                    NTP TR 484. http://ntp.niehs.nih.gov/                   Fundam. Appl. Toxicol. 16: 830–840.                   for 2-Butoxyethanol (EGBE). Vol. 68.
                                                    ?objectid=070AC403-B110-CA79-                      66. NTP. 1993. NTP technical report on                     European Commission.
                                                    3A23AF79DE7B752A.                                       toxicity studies of ethylene glycol ethers:      78. Bringmann, G., Kuhn, R. 1982. Results of
                                               53. Zeiger, E., Anderson, B., Haworth, S.,                   2-methoxyethanol, 2-ethoxyethanol, 2-                 the toxic action of water pollutants on
                                                    Lawlor, T., Mortelmans, K. 1992.                        butoxyethanol (CAS Nos. 109–86–4,                     Daphnia magna in an improved
                                                    Salmonella mutagenicity tests: V Results                110–80–5, 111–76–2) administered in                   standardized procedure. Z. Wasser
                                                    from the testing of 311 chemicals.                      drinking water to F344/N rats and                     Abwasser Forsch. 15(1): 1–6. (In German)
                                                    Environ. Mol. Mutagen. 19: 2–141.                       B6C3F1 mice. National Toxicology                 79. Juhnke, I., Luedemann, D. 1978. Results
                                               54. Gollapudi, B.B., Barber, E.D., Lawlor,                   Program. Research Triangle Park, NC. 26;              of the study of 200 chemical compounds
                                                    T.E., Lewis, S.A. 1996. Re-examination                  NIH Publication 93–3349.                              on acute fish toxicity using the Golden
                                                                                                                                                                  Orfe test. Z. Wasser Abwasser Forsch.
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                                                    of the mutagenicity of ethylene glycol             67. Nelson. B.K., Setzer, J.V., Brightwell,
                                                    monobutyl ether to Salmonella tester                    W.S., Mathinos, P.R., Kuczuk, M.H.,                   11(5): 161–164. (In German)
                                                    strain TA97a. Mutat. Res. 370: 61–64.                   Weaver, T.E., Goad, P.T. 1984.                   80. Dow Chemical Co. 1979. Toxicity of
                                               55. Chiewchanwit, T., Au, W.W. 1995.                         Comparative inhalation teratogenicity of              Dowanol EB to freshwater organisms
                                                    Mutagenicity and cytotoxicity of 2-                     four glycol ether solvents and an amino               (redactor: Bartlett), 31 August 1979. As
                                                    butoxyethanol and its metabolite, 2-                    derivative in rats. Environ. Health                   cited in Ref. 77.
                                                    butoxyacetaldehyde, in Chinese hamster                  Perspect. 57: 261–271.                           81. Dawson, G.W., Jennings, A.L.,
                                                    ovary (CHO–AS52) cells. Mutat. Res.                68. Tyl, R.W., Millicovsky, G., Dodd, D.E.,                Drozdowski, D., Rider, E. 1975. The
                                                    334: 341–346.                                           Pritts, I.M., France, K.A., Fisher, L.C.              acute toxicity of 47 industrial chemicals



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                                                                     Federal Register / Vol. 80, No. 195 / Thursday, October 8, 2015 / Proposed Rules                                          60825

                                                    to fresh and saltwater fishes. Journal of          SUMMARY:   In this document the                       Documents in Rulemaking Proceedings,
                                                    Hazardous Materials. 1: 303–318.                   Commission revises its Schedule of                    63 FR 24121 (1998).
                                               82. INERIS. 1999. Détermination de la                  Regulatory Fees to recover an amount of                  • Electronic Filers: Comments may be
                                                    toxicité aiguë du 2-butoxyethanol vis-à-                                                              filed electronically using the Internet by
                                                    vis de Oncorhynchus mykiss,
                                                                                                       $339,844,000 that Congress has required
                                                    unpublished, Ba746f-CGR21427.                      the Commission to collect for fiscal year             accessing the ECFS.
                                                    Verneuil-en-Halatte, France, 14                    2015. Section 9 of the Communications                    • Paper Filers: Parties who choose to
                                                    december 1999, INERIS: 10. As cited in             Act of 1934, as amended, provides for                 file by paper must file an original and
                                                    Ref. 77.                                           the annual assessment and collection of               one copy of each filing. If more than one
                                               83. Bridie, A.L., Wolff, C.J.M., Winter, M.             regulatory fees under sections 9(b)(2)                docket or rulemaking number appears in
                                                    1979. The acute toxicity of some                   and 9(b)(3), respectively, for annual                 the caption of this proceeding, filers
                                                    petrochemicals to goldfish. Water Res.                                                                   must submit two additional copies for
                                                                                                       ‘‘Mandatory Adjustments’’ and
                                                    13(7): 623–626.                                                                                          each additional docket or rulemaking
                                               84. Price, K.S., Waggy, G.T., Conway, R.A.              ‘‘Permitted Amendments’’ to the
                                                    1974. Brine shrimp bioassay and                    Schedule of Regulatory Fees.                          number.
                                                    seawater BOD of petrochemicals. Journal                                                                     Æ Filings can be sent by hand or
                                                                                                       DATES: Comments are due November 9,
                                                    WPCF. 46(1): 63–76.                                                                                      messenger delivery, by commercial
                                                                                                       2015 and Reply Comments are due                       overnight courier, or by first-class or
                                               85. Bringmann, G., Kuhn, R. 1978. Threshold
                                                                                                       December 7, 2015.                                     overnight U.S. Postal Service mail. All
                                                    Values of Substances Harmful to Water
                                                    for Blue Algae (Microcystis aeruginosa)            FOR FURTHER INFORMATION CONTACT:                      filings must be addressed to the
                                                    and Green Algae (Scenedesmus                       Roland Helvajian, Office of Managing                  Commission’s Secretary, Office of the
                                                    quadricauda) in Tests Measuring the                Director at (202) 418–0444.                           Secretary, Federal Communications
                                                    Inhibition of Cellular Propagation. Vom
                                                    Wasser. 50:45 60 (in German) (English              SUPPLEMENTARY INFORMATION: This is a                  Commission.
                                                    Abstract), Tr 80 0201, Literature                  summary of the Commission’s Further                      Æ All hand-delivered or messenger-
                                                    Research Company: 22 p.                            Notice of Proposed Rulemaking                         delivered paper filings for the
                                               86. Bringmann, G., Kuhn, R. 1978. Testing of            (FNPRM), FCC 15–108, MD Docket No.                    Commission’s Secretary must be
                                                    Substances for Their Toxicity Threshold:           15–121, adopted on September 1, 2015                  delivered to FCC Headquarters at 445
                                                    Model Organisms Microcystis                        and released on September 2, 2015.                    12th St. SW., Room TW–A325,
                                                    (Diplocystis) aeruginosa and                                                                             Washington, DC 20554. The filing hours
                                                    Scenedesmus quadricauda. Mitt. Int.                I. Administrative Matters                             are 8:00 a.m. to 7:00 p.m. All hand
                                                    Ver. Theor. Angew. Limnol. 21: 275 284.
                                                                                                       A. Initial Regulatory Flexibility Analysis            deliveries must be held together with
                                               87. Dill, DC, Milazzo, D.P. 1988. Dowanol PM
                                                    Glycol Ether: Evaluation of the toxicity                                                                 rubber bands or fasteners. Any
                                                                                                         1. As required by the Regulatory                    envelopes and boxes must be disposed
                                                    to the green alga, Selenastrum
                                                    capricornutum Printz. Dow Chemical
                                                                                                       Flexibility Act of 1980 (RFA),1 the                   of before entering the building.
                                                    Company. EPA Document Control                      Commission has prepared an Initial                       Æ Commercial overnight mail (other
                                                    Number 86–890001160. 18 pages.                     Regulatory Flexibility Analysis (FRFA)                than U.S. Postal Service Express Mail
                                               88. INERIS. 1999. Détermination de la                  relating to this Further Notice of                    and Priority Mail) must be sent to 9300
                                                    toxicité chronique du 2-butoxyethanol             Proposed Rulemaking.                                  East Hampton Drive, Capitol Heights,
                                                    vis-à-vis de Daphnia magna, Ba746a–                                                                     MD 20743.
                                                    CGR21427. Verneuil-en-Halatte, France,             B. Initial Paperwork Reduction Act of
                                                                                                       1995 Analysis                                            Æ U.S. Postal Service first-class,
                                                    15 december 1999, INERIS: 13. As cited
                                                    in Ref. 77.
                                                                                                                                                             Express, and Priority mail must be
                                                                                                         2. This document does not contain                   addressed to 445 12th Street SW.,
                                               89. INERIS. 2001. Essai poisson 21 jours,
                                                    Danio rerio, unpublished report, N°                new or modified information collection                Washington, DC 20554.
                                                    22685, 05.11.2001. As cited in Ref. 77.            requirements subject to the Paperwork                    4. People with Disabilities: To request
                                                                                                       Reduction Act of 1995 (PRA), Public                   materials in accessible formats for
                                               List of Subjects in 40 CFR Part 372                     Law 104–13. In addition, therefore, it                people with disabilities (braille, large
                                                 Environmental protection,                             does not contain any new or modified                  print, electronic files, audio format),
                                               Community right-to-know, Reporting                      information collection burden for small               send an email to fcc504@fcc.gov or call
                                               and recordkeeping requirements, and                     business concerns with fewer than 25                  the Consumer & Governmental Affairs
                                               Toxic chemicals.                                        employees, pursuant to the Small                      Bureau at 202–418–0530 (voice), 202–
                                                 Dated: September 24, 2015.                            Business Paperwork Relief Act of 2002,                418–0432 (tty).
                                               Arnold E. Layne,
                                                                                                       Public Law 107–198, see 44 U.S.C.
                                                                                                       3506(c)(4).                                           D. Ex Parte Information
                                               Director, Office of Information Analysis and                                                                     5. This proceeding shall be treated as
                                               Access.                                                 C. Filing Instructions                                a ‘‘permit-but-disclose’’ proceeding in
                                               [FR Doc. 2015–25674 Filed 10–7–15; 8:45 am]                                                                   accordance with the Commission’s ex
                                                                                                         3. Pursuant to sections 1.415 and
                                               BILLING CODE 6560–50–P                                                                                        parte rules. Persons making ex parte
                                                                                                       1.419 of the Commission’s rules, 47 CFR
                                                                                                       1.415, 1.419, interested parties may file             presentations must file a copy of any
                                                                                                       comments and reply comments on or                     written presentation or a memorandum
                                               FEDERAL COMMUNICATIONS                                  before the dates indicated on the first               summarizing any oral presentation
                                               COMMISSION                                              page of this document. Comments may                   within two business days after the
                                                                                                       be filed using the Commission’s                       presentation (unless a different deadline
                                               47 CFR Part 1                                                                                                 applicable to the Sunshine period
                                                                                                       Electronic Comment Filing System
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                                               [MD Docket No. 15–121; FCC 15–108]                      (ECFS). See Electronic Filing of                      applies). Persons making oral ex parte
                                                                                                                                                             presentations are reminded that
                                               Assessment and Collection of                              1 See 5 U.S.C. 603. The RFA, see 5 U.S.C. 601–      memoranda summarizing the
                                               Regulatory Fees for Fiscal Year 2015                    612, has been amended by the Small Business           presentation must list all persons
                                                                                                       Regulatory Enforcement Fairness Act of 1996           attending or otherwise participating in
                                               AGENCY:  Federal Communications                         (SBREFA), Public Law 104–121, Title II, 110 Stat.
                                               Commission.                                             847 (1996). The SBREFA was enacted as Title II of
                                                                                                                                                             the meeting at which the ex parte
                                                                                                       the Contract with America Advancement Act of          presentation was made, and summarize
                                               ACTION: Proposed rule.
                                                                                                       1996 (CWAAA).                                         all data presented and arguments made


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Document Created: 2015-12-15 08:43:13
Document Modified: 2015-12-15 08:43:13
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionProposed Rules
ActionDenial of petition.
DatesEPA denied this petition on September 24, 2015.
ContactDaniel 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/.
FR Citation80 FR 60818 
CFR AssociatedEnvironmental Protection; Community Right-To-Know; Reporting and Recordkeeping Requirements and Toxic Chemicals

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