[Federal Register Volume 78, Number 236 (Monday, December 9, 2013)]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-28365]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 372
[EPA-HQ-TRI-2013-0393; FRL 9903-44-OEI]
Chlorsulfuron; Community Right-to-Know Toxic Chemical Release
AGENCY: Environmental Protection Agency (EPA).
ACTION: Denial of Petition.
SUMMARY: EPA is denying a petition to remove chlorsulfuron from 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
chlorsulfuron 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 chlorsulfuron meets the listing criterion of EPCRA
section 313(d)(2)(C) due to its toxicity to aquatic plants.
DATES: EPA denied this petition on November 18, 2013.
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@example.com, 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/.
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 chlorsulfuron. Potentially affected
categories and entities may 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, 221119, 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?
EPA has established a docket for this action under Docket ID No.
EPA-HQ-TRI-2013-0393. All documents in the docket are listed in the
www.regulations.gov index. Although listed in the index, some
information is not publicly available, e.g., CBI or other information
whose disclosure is restricted by statute. Certain other material, such
as copyrighted material, will be publicly available only in hard copy.
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.
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
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:
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
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
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
III. What is the description of the petition?
On May 18, 2012, EPA received a petition from DuPont Crop
Protection (DuPont), Technology Sciences Group Inc. (TSG) requesting
EPA to delete chlorsulfuron (Chemical Abstracts Service Registry Number
(CASRN) 64902-72-3) from the list of chemicals subject to reporting
under EPCRA section 313 and PPA section 6607 (Reference (Ref. 1)).
Chlorsulfuron was added to the EPCRA section 313 chemical list on
November 30, 1994, based on concerns for developmental and reproductive
toxicity (59 FR 61432). DuPont contends that newer studies show that
chlorsulfuron does not cause developmental or reproductive toxicity and
therefore no longer meets the EPCRA section 313(d)(2) criteria for
listing. While the petition addressed the acute human health effects
criterion of section 313(d)(2)(A) and chronic human health effects
criterion of section 313(d)(2)(B), it did not address the environmental
effects criterion of section 313(d)(2)(C).
IV. What is EPA's evaluation of the human health toxicity of
EPA's evaluation of the toxicity of chlorsulfuron included a review
of the original 1994 listing decision (59 FR 1788, January 12, 1994 and
59 FR 61432, November 30, 1994), the 2002 Chlorsulfuron Toxicology
Chapter (Ref. 2), the Federal Register Notice for Chlorsulfuron
Pesticide Tolerance (67 FR 52866, August 14, 2002), and the
Reregistration Eligibility Decision (RED) for Chlorsulfuron (Ref. 3).
EPA also reviewed the findings of relevant studies published since the
RED for chlorsulfuron was published (Ref. 4). Unit IV.A. below outlines
evidence of human health toxicity from these existing EPA hazard
characterizations and Unit IV.B. provides a brief summary of the
findings from recently published studies. Unit IV.C. provides a summary
of the ecological toxicity of chlorsulfuron from the existing EPA
A. Review of the Reregistration Eligibility Decision for Chlorsulfuron
1. Kinetics and Metabolism
EPA concluded that chlorsulfuron is rapidly absorbed, metabolized,
and eliminated when administered orally to rats (Ref. 2). There are no
differences in absorption, distribution, and elimination of
chlorsulfuron related to sex, dose, or treatment regimen. In one study,
the major routes of elimination were found to be urine (58-72%) and
feces (20-35%) with small amounts (0.1-0.2%) remaining in tissues
(primarily in the liver and whole blood) three days after dosing (Ref.
5). This same study identified the major metabolic pathway of
chlorsulfuron as the contraction of the sulfonylurea linkage followed
by oxidation and hydroxylation to form IN-70941, IN-70942, Metabolite
P5 (desmethyl IN-70942), and Metabolite P4 (OH-desmethyl IN-70942). The
cleavage of the sulfonylurea linkage to form Metabolite IN-E9260 was
identified as the minor metabolic pathway. No additional information on
the absorption, distribution, metabolism, and excretion of
chlorsulfuron was found in the literature.
2. Effects of Acute Exposure
EPA concluded that chlorsulfuron has no significant acute toxicity
(Ref. 2). The conclusion was based on the results of a dermal study
(Ref. 6), an inhalation study (Ref. 7) and on an oral study (Ref. 8).
3. Effects of Repeated Exposure
a. Effects of subchronic exposure. As stated in the 2002
Chlorsulfuron Toxicology Chapter (Ref. 2), there are few subchronic
studies of chlorsulfuron in the literature. No 21- or 90-day dermal
toxicity studies or 90-day inhalation studies were identified. Two
subchronic oral toxicity studies were identified and summarized in the
2002 Chlorsulfuron Toxicology Chapter (Ref. 2). In a 90-day oral
toxicity study, Smith et al. (Ref. 9) administered chlorsulfuron (100%)
to 10 ChR-CD[supreg]-1 mice/sex/dose at dietary concentrations of 0,
500, 2,500, 5,000, and 7,500 ppm (equivalent to 0, 150, 783, 1,557,
2,130 milligrams/kilogram/day (mg/kg/day) in males and 0, 220, 1,214,
2,134, 3,176 mg/kg/day in females). The authors reported a lowest-
observed-adverse-effect level (LOAEL) of 2,130 mg/kg/day based on
increased incidence of retinal dysplasia. This study, however, lacked
clinical chemistry and organ weight data. In a 6-month oral toxicity
study, Schneider et al. (Ref. 10) administered chlorsulfuron (95%) to
purebred Beagle dogs (4/sex/dose) in the diet at dose levels of 0, 100,
500, and 2,500 ppm (equivalent to 0, 3.7, 18.5, and 82.3 mg/kg/day).
The authors reported a LOAEL of 82.3 mg/kg/day based on decreased body
weight gain in females. Female body weight decreases were slight (91%,
93%, and 87% of control group in the low, mid, and high dose groups,
respectively) and body weight decreases were observed in the treatment
groups prior to treatment. The authors also noted that high-dose
females also exhibited a lower food intake. Additionally, it does not
appear that the animals were randomized by body weight at the beginning
of the study, which makes these body weight findings more difficult to
interpret. No other treatment-related effects were observed in any
hematological, clinical chemistry, organ weights, or gross and
microscopic pathology in animals of either sex. EPA concluded that the
subchronic oral database does not identify toxicity to any particular
target organ (Ref. 2).
b. Carcinogenicity. EPA concluded there is no evidence of
carcinogenicity in rats or mice following oral exposure to
chlorsulfuron (Ref. 2). In a chronic toxicity study, Wood et al., (Ref.
11) administered chlorsulfuron (95%) to 80 CD[supreg] rats/sex/dose in
the diet at dose levels of 0, 100, 500, and 2,500 (equivalent to 0, 5,
25, and 125 mg/kg/day) for two years. The authors reported that the
unilateral incidence of interstitial cell tumors was within the known
spontaneous range for CD[supreg] rats and that there were no other
changes suggestive of a treatment-related tumorigenic effect in the
testes. In a similar carcinogenicity study, Wood et al., (Ref. 12)
administered chlorsulfuron (91.9-95%) to 80 CD-1 mice/sex/dose in the
diet at dose levels of 0, 100, 500, and 5,000 ppm (equivalent to 0, 15,
108, and 750 mg/kg/day) for two years. The authors reported no
treatment-related increase in tumor incidence. No additional
carcinogenicity studies were identified in the literature.
4. Reproductive and Developmental Toxicity
While the rabbit toxicity study cited in the 1994 Federal Register
TRI listing of chlorsulfuron (59 FR 1788, January 12, 1994) reported a
treatment-related increase in fetal resorptions and decrease in the
mean incidence of live fetuses per litter at 75 mg/kg/day (Ref. 13),
the results were not strongly indicative of a dose-response effect,
were not able to be replicated in a follow-up study, and have recently
been reanalyzed with improved methods. In this 1980 study cited in the
original TRI listing of chlorsulfuron, Hoberman (Ref. 13) administered
chlorsulfuron to pregnant female New Zealand white rabbits by oral
intubation at doses of 0, 10, 25, and 75 mg/kg on days 6-19 of
gestation. The author reported no significant changes in maternal body
weight, uterine weight, ovarian weight, corpora lutea, visceral
anomalies, or implantations. The author concluded that the increased
mean incidence of resorptions in the highest dose group (31.3% versus
11.6% in the control group) and the decreased mean of live fetuses in
the highest dose group (59.8% versus 88.5% in the control group) were
significant treatment-related effects. A subsequent 1991 study
performed in accordance with EPA guidelines (Ref. 14), however, was not
able to replicate these findings using similar methods and higher doses
(Ref. 15). This study concluded that chlorsulfuron does not cause an
increase in fetal resorptions or decrease in fetal viability in rabbits
up to 1,000 mg/kg/day, the highest dose tested (Ref. 15). Moreover, the
2002 Chlorsulfuron Toxicology Chapter (Ref. 2), the Federal Register
Notice on Chlorsulfuron Pesticide Tolerance (67 FR 52866, August 14,
2002), and the Reregistration Eligibility Decision for Chlorsulfuron
(Ref. 3) do not include fetal resorptions or decreased fetal viability
as a part of the chlorsulfuron hazard characterization.
The 1994 Federal Register TRI listing of chlorsulfuron (59 FR 1788,
January 12, 1994) also cited a slight treatment-related decrease in
maternal fertility in the F3 generation observed in a rat chronic
toxicity study (Ref. 11), but these findings have since been
questioned. The design of this study is briefly summarized in the above
Carcinogenicity Section (Unit IV.A.3.b.). The 2002 Chlorsulfuron
Toxicology Chapter (Ref. 2) and the Federal Register Notice on
Chlorsulfuron Pesticide Tolerance (67 FR 52866, August 14, 2002)
concluded that the findings of this study are of questionable
significance due to several study deficiencies. This study did not
satisfy the current guideline (Ref. 14) requirements and contains
numerous deficiencies including but not limited to: (1) No assessment
of estrous cyclicity, (2) no assessment of male reproductive
performance, (3) no gross pathology or histopathology examination of
parental animals, (4) no assessment of developmental landmarks, and (5)
histopathology examinations were conducted only for the F3B generation
(Ref. 2; 67 FR 52866, August 14, 2002). As such, EPA classified this
study as unacceptable.
EPA concluded that developmental toxicity was observed in both the
rabbit (Ref. 15) and rat (Ref. 16), as evidenced by decreased fetal
body weight (Ref. 2). However, treatment-related fetal body weight
decreases in the rabbit study (Ref. 15) were slight (10%), occurred at
a moderately high dose (LOAEL of 400 mg/kg/day), and were observed in
the absence of other developmental effects. Additionally, decreased
fetal body weight occurred in the presence of decreased maternal body
weight. Adjusted maternal body weight gains throughout the study (days
0-29) in the highest treatment groups (original study: 200, 400 mg/kg/
day; supplemental study: 400, 1,000 mg/kg/day) were substantially lower
than those in the control group (78%, 54%, 43%, and 43% of control,
respectively). In the original and supplemental studies, however, the
adjusted maternal body weight gains in the treatment groups appeared to
fall within the range of normal variation of control group animals.
Also, the final adjusted maternal body weights in both these studies
were not statistically different among treatment and control groups.
Furthermore, it is not apparent that the study authors examined food
consumption or food efficiency in either study. It is important to note
that a dose of 1,000 mg/kg/day resulted in a high percentage of
maternal mortality (i.e., much greater than 10%), which makes the
developmental data in this dose group unreliable and of limited value
based on the EPA Developmental Test Guidelines (Ref. 17). In the rat
study, fetal toxicity was limited to decreased fetal weight in the
highest dose group (1,500 mg/kg/day) and there were no teratogenic
effects observed (Ref. 16). Dams in the highest dose group exhibited
vaginal discharge associated with alopecia. Based on these data, the
authors determined that the maternal LOAEL was 500 mg/kg/day and the
developmental LOAEL was 1,500 mg/kg/day for rats.
A few mutagenicity studies were identified in the 2002
Chlorsulfuron Toxicology Chapter (Ref. 2), but none of these studies
provided evidence of mutagenicity. Therefore, EPA concluded that there
is no concern for mutagenicity of chlorsulfuron.
There is no evidence of neurotoxicity in any study of
7. Other Chronic Toxicity
In addition to the body weight findings from Alvarez (Refs. 15 and
16) discussed in the above Reproductive and Developmental Toxicity
Section (Unit IV.A.4), several other chronic studies derived
chlorsulfuron LOAELs based on observed changes in body weight and/or
body weight gain. Wood et al. (Ref. 11) reported a LOAEL of 25 mg/kg/
day based on decreased body weight in male rats in the highest dose
groups (25 and 125 mg/kg/day). The reported decrease in body weight,
however, was slight (4-9% and 5-10%, respectively) and decreased body
weight gain was not significantly different between the highest
treatment group and the control group when measured over the entire
study. Additionally, no changes were reported in female rats and no
other treatment-related effects were reported in the study. Wood et al.
(Ref. 12) reported a LOAEL of 750 mg/kg/day due to decreased body
weight and body weight gain in male and female mice. This high LOAEL,
however, is indicative of moderately low to low chlorsulfuron toxicity.
Atkinson et al. (Ref. 18) reported a LOAEL of 215 mg/kg/day based on
decreased body weight gain in female Beagle dogs. While these reported
changes were observed in the absence of decreased food consumption,
they were not found to be statistically significant. Moreover, body
weight gains decreased in the highest dose group in the first half of
the study (weeks 1-26), but there was no treatment-related effect on
overall body weight gain over the entire study (weeks 1-52). Based on
these findings, the evidence for body weight and body weight changes is
not sufficient to conclude that chlorsulfuron is reasonably anticipated
to cause serious or irreversible systemic toxicity.
B. Review of Studies Published Since the Reregistration Eligibility
Decision for Chlorsulfuron
EPA identified and reviewed all relevant studies on chlorsulfuron
that have been published since the RED for Chlorsulfuron (Ref. 3) was
issued. After review of the recent literature, EPA concluded that there
were no acceptable studies that strongly suggest either acute or
chronic toxicity of chlorsulfuron (Ref. 4). Below are brief summaries
of the findings from these studies identified in the recent literature.
1. Mylchreest Reproductive Study
In a 2-generation reproduction study, Mylchreest (Ref. 19)
administered chlorsulfuron Crl:CD[supreg](SD)IGS BR rats via the diet.
The administered dose levels were 0, 100, 500, 2,500, and 7,500 ppm
(average daily doses of 0, 6, 30, 151, 456 mg/kg/day in males and 0, 7,
39, 188, 591 mg/kg/day in females) throughout the 10-week premating
period and throughout gestation and lactation. This study replicated
the design of the Wood (Ref. 11) study with updates to ensure
compliance with new EPA guidelines (Ref. 14) and good laboratory
No treatment-related effects were reported in litter size, live
birth index, number born dead, viability and lactation indices,
clinical examinations, sex ratio, sexual maturation, organ weights, and
gross or microscopic observations. The first generation (F1) sex ratio
was significantly higher in the highest dose group (55% versus 45%
males in the control group), but the authors did not consider this a
treatment-related effect because it fell within the historical control
range (45-59%). Lower offspring body weights were observed in the
highest dose group in both generations, but these differences were not
considered adverse because the magnitude of body weight changes was
slight (5-7%) and the potential effect of larger litter size on pup
weight. The authors reported an offspring no-observed-adverse-effect
level (NOAEL) of 456 mg/kg/day in males and 498 mg/kg/day in females
(note: the administered dose of 591 mg/kg-day was adjusted for
decreased intake during gestation), the highest dose tested.
There were no treatment-related effects on ovarian follicles counts
in F1 females, sperm and estrous cycle parameters in parental (P) and
F1 adults, mating, precoital interval, fertility, gestation length,
number of implantation sites, and implantation efficiency in either
generation. As such, the authors reported a reproductive NOAEL of 456
mg/kg/day in males and 498 mg/kg/day in females (note: the administered
dose of 591 mg/kg-day was adjusted for decreased intake during
gestation), the highest dose tested. These results demonstrate that
chlorsulfuron did not cause any treatment-related reproductive toxicity
and its effects on parental body weight and food efficiency indicate
moderately low to low toxicity.
2. Other Studies
In addition to the Mylchreest (Ref. 19) study, three other recent
chlorsulfuron toxicity studies were identified in the literature. It is
difficult to draw conclusions about these studies' findings, however,
due to the lack of basic information provided by the authors. The
studies contained numerous deficiencies including, no details on animal
species or strain, the body weights of study animals were not reported
(only an overall range was given), the age of the test animals was not
reported, analytical methods were not described nor was their
methodology for the different tests, etc. Given these deficiencies,
findings from these studies were of very limited use in the
determination of hazard for chlorsulfuron.
In an acute oral toxicity study, Rudaya et al. (Ref. 20)
administered chlorsulfuron potassium salt intragastrically in male and
female non-pedigreed white rats, male and female mice, and male rabbits
of the Chinchilla line. The authors concluded that the LD50
(i.e., the dose of a chemical that is lethal to 50 percent of the test
organisms) was 5,580 1,002 mg/kg for male rats, 5,500
729 mg/kg for female rats, 2,050 367 mg/kg
for male mice, 2,460 312 mg/kg for female mice, and 3,900
451 mg/kg for male rabbits.
In a chronic oral toxicity study, Rudaya et al. (Ref. 21) examined
the effect of chlorsulfuron potassium salt administered
intragastrically in male white rats. Chlorsulfuron potassium salt was
administered orally at dose levels of 0, 0.558, 5.58, and 55.8 mg/kg
over 9 months. The authors reported several effects of chlorsulfuron
potassium salt on the liver, kidneys, heart, and thyroid gland, and on
behavior, but it is unclear from the study whether any of these effects
were statistically or biologically significant. Based on these
findings, the authors concluded that the no-effect dose of
chlorsulfuron potassium salt was 0.558 mg/kg.
Rakitsky and Beloyedova (Ref. 22) studied the acute and chronic
effects of several sulfonylurea herbicides, including chlorsulfuron, in
rats, mice, dogs, and rabbits. The authors measured central nervous
function, liver, kidney, and hematologic function up to several months
after exposure. The authors reported an oral LD50 in rats of
5,545-6,293 mg/kg in males and females, respectively, and a dermal
LD50 of 2,500 mg/kg in rabbits. The authors also reported an
LC50 (4 hours) of >5,900 mg/m\3\ in rats. The authors
reported a chronic no-observed-effect level (NOEL) of 0.2-5 mg/kg/day
for rats, 108 mg/kg/day for mice, and 60.6 mg/kg/day for dogs, but they
did not indicate from which health endpoints these NOELs were derived.
C. Review of Ecological Effects
1. Environmental Fate and Degradation
Chlorsulfuron is likely to be persistent and highly mobile in the
environment. It may be transported to non-target areas via runoff and/
or spray drift (Ref. 3). Degradation in the aquatic environment occurs
primarily through hydrolysis at low pH (23 day half-life at pH 5) but
it is stable in neutral to basic environments (Ref. 23). Aerobic
aquatic metabolism data are not available; however, aerobic soil
metabolism data suggest that aerobic aquatic metabolism may occur. Soil
degradation half-lives have been reported to vary from 12 to 183 days
2. Ecological Toxicity and Hazard
a. Toxicity to aquatic animals. Experimental toxicity values are
reported only for a few surrogate species. Estuarine data are limited
to a crustacean, a mollusk, and a fish. No amphibians or reptiles were
tested (Ref. 3). Chlorsulfuron is practically nontoxic to both
freshwater and marine/estuarine fish and slightly toxic to estuarine/
marine invertebrates when measured under acute conditions (Ref. 3).
Chronic exposure of rainbow trout (Oncorhynchus mykiss) to
chlorsulfuron resulted in a No Observed Effect Concentration (NOEC) of
32 mg/L (Ref. 25). The observed NOEC for water fleas (Daphnia magna)
was 20 mg/L (Ref. 26).
b. Toxicity to aquatic plants. In contrast to the data for aquatic
animals, for some species of aquatic plants the toxicity of
chlorsulfuron is very high. (Ref. 3). Duckweed (Lemna gibba) was the
most sensitive aquatic vascular plant (Refs. 27 and 28). Growth rate
studies using endpoints for both biomass (dry weight) and the number of
normal fronds found 14 day EC50's (concentration at which
50% of the plants are affected) of 3.5 x 10-\4\ milligrams
per liter (mg/L) and 4.2 x 10-\4\ mg/L respectively (Table
I). The 14 day NOEC for both biomass and the number of normal fronds
was 0.24 [mu]g/L (micrograms per liter) (Table I). The most sensitive
nonvascular aquatic plant was the green alga Pseudokirchneriella
subcapitata (formerly Skeletonema costatum) (120 hour (hr)
EC50 = 0.05 mg/L; 120 hr NOEC = 0.0094 mg/L) (Refs. 29 and
30) and measured acute toxicity to the freshwater blue-green alga
Anabaena flos-aquae was also quite high (Refs. 31 and 32) (Table I).
Table I--Summary of Acute and Chronic Toxicity Data of Chlorsulfuron to Freshwater Aquatic Plants and Algae
Species Common name Toxicity Citation
Pseudokirchneriella subcapitata Green Algae............ 120 hr EC50 = 0.05 mg/L Refs. 29 and 30.
(formerly known as Selenastrum (cell density); 120 hr
capricornutum). NOEC = 0.0094 mg/L
Lemna gibba.......................... Freshwater Duckweed.... 14 day EC50 = 3.5 x 10- Refs. 27 and 28.
4 mg/L (biomass); 14
day EC50 = 4.2 x 10-4
mg/L (number of normal
fronds); 14 day NOEC =
2.4 x 10-4 mg/L (for
both biomass and
Anabaena flos-aquae.................. Cyanobacteria.......... 120 hr EC50 = 0.609 mg/ Refs. 31 and 32.
L (area under the
growth curve); 120 hr
EC50 = 1.77 mg/L (mean
specific growth rate);
120 hr EC50 = 0.807 mg/
L (cell counts); 120
hr NOEC = 0.236 mg/L
(area under the growth
curve); 120 hr NOEC =
0.485 mg/L (mean
specific growth rate);
120 hr NOEC = 0.236 mg/
L (cell counts).
c. Toxicity to terrestrial animals. Chlorsulfuron is practically
nontoxic to birds and mammals in acute exposure regimes and
chlorsulfuron is also practically nontoxic to birds given subacute
dietary exposures (Refs. 3 and 33). Chronic toxicity to northern
bobwhite quail (Colinus virginianus) included significant reductions in
female body weight, decreased 14-day old survival, decreased number of
normal hatchlings, decreased number of viable embryos (Ref. 34).
d. Toxicity to terrestrial plants. Chlorsulfuron exposure is known
to affect nontarget plant fruit or seed production and may cause
visible disease symptoms days or weeks after exposure (Ref. 3). Short
term symptoms include spotting, leaf puckering or twisting, as well as
chlorosis and discolored veins. Developmental and reproductive effects
of exposure may not become apparent until three or four months after
exposure. Reduced fruit development and decreased seed production due
to chlorsulfuron exposure has been observed in canola, smartweed,
soybean, and sunflower. Thus these types of chronic toxicity effects
may be difficult to recognize in the field due to the time lag inherent
in their expression.
Available experimental toxicity data for terrestrial plants (Refs.
33 and 34) reveals EC25 (concentration at which 25 percent
of the organisms are affected) values as low as 1.0 x 10-5
lbs ai/A (pounds active ingredient per acre) measured for vegetative
vigor (shoot dry weight) of nontarget plants (sugar beet). NOEC values
of 5.4 x 10-6 lbs ai/A for vegetative vigor (shoot dry
weight) have been measured for onion and sugar beet.
D. Summary of Human Health and Ecological Toxicity Evaluation
Based on previous EPA hazard characterizations (Refs. 2 and 3; 67
FR 52866, August 14, 2002), there is sufficient evidence to support a
low concern for human toxicity from exposure to chlorsulfuron. A more
recent guideline (Ref. 14) study (Ref. 15) was not able to replicate
findings from one of the studies upon which the addition of
chlorsulfuron to the list of toxic chemicals subject to reporting
requirements of EPCRA section 313 and section 6607 of the PPA was based
(Ref. 13). Additionally, recent assessments of the studies cited in the
listing of chlorsulfuron (Refs. 11 and 13) question the validity of
these studies' methods and conclusions (Ref. 2; 67 FR 52866, August 14,
Additionally, no studies that strongly suggest either acute or
chronic toxicity of chlorsulfuron were identified in the literature
since the publication of the RED for chlorsulfuron (Ref. 3). A
relatively recent guideline (Ref. 14) study (Ref. 19) was not able to
replicate findings from another one of the studies upon which the
addition of chlorsulfuron to the EPCRA section 313 toxic chemical list
was based (Ref. 11). The reported findings from the other additional
studies (Refs. 20, 21, and 22) were of very limited use in the
determination of hazard for chlorsulfuron due to the study deficiencies
previously outlined. While treatment-related body weight changes were
observed in the Mylchreest study (Ref. 19), these changes were observed
at a relatively high dose level (close to 500 mg/kg/day) and were
observed in the absence of any other treatment-related effects.
Based on EPA's review of the available data, there is no compelling
evidence of the acute toxicity, carcinogenicity, reproductive or
developmental toxicity, mutagenicity, or other serious chronic toxicity
of chlorsulfuron. While treatment-related body weight changes were
observed in some studies, the evidence for these changes is not
sufficient to conclude
that chlorsulfuron is expected to cause serious or irreversible
systemic toxicity. Therefore, chlorsulfuron is not reasonably
anticipated to cause acute or chronic toxicity in humans.
Chlorsulfuron has low toxicity to most aquatic and terrestrial
animals. However, chlorsulfuron is highly toxic to some species of
aquatic plants. Toxicity values (EC50s) for aquatic plants
are as low as 3.5 x 10-4 mg/L indicating very high toxicity
V. What is EPA's rationale for the denial?
EPA is denying the petition to delete chlorsulfuron from the EPCRA
section 313 list of toxic chemicals. This denial is based on EPA's
conclusion that chlorsulfuron can reasonably be anticipated to cause
toxicity to aquatic plants. Chlorsulfuron has been shown to have an
adverse effect on aquatic plant growth at very low concentrations with
an EC50 of 3.5 x 10-4 mg/L for duckweed and an
EC50 of 0.05 mg/L for green algae as well as EC50
of 0.609 mg/L for blue green algae. Therefore, EPA has concluded that
chlorsulfuron meets the EPCRA section 313(d)(2)(C) listing criteria
based on the available environmental toxicity data.
Because EPA believes that chlorsulfuron is highly toxic to aquatic
plants, EPA does not believe that an exposure assessment is appropriate
for determining whether chlorsulfuron meets the criteria of EPCRA
section 313(d)(2)(C). 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).
EPA has established an official public docket for this action under
Docket ID No. EPA-HQ-TRI-2013-0393. 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
1. DuPont Crop Protection. 2012. Petition to Delete
Chlorsulfuron from TRI List. DuPont Crop Protection (DuPont),
Technology Sciences Group Inc. (TSG). May 18, 2012.
2. U.S. EPA. 2002. Toxicology Chapter for Chlorsulfuron. Health
Effects Division, Office of Pesticide Programs. July 17, 2002.
3. U.S. EPA. 2005. Reregistration Eligibility Decision for
Chlorsulfuron. Office of Pesticide Programs. May 20, 2005.
4. U.S. EPA, OEI. 2013. Memorandum from Jocelyn Hospital,
Toxicologist, Analytical Support Branch to Daniel Bushman, TRI
Petitions Coordinator and Chemical List Manager, Analytical Support
Branch. April 24, 2013. Subject: Review of Chlorsulfuron Studies
Published Since Publication of the Reregistration Decision for
5. Hawking, D., Epsom, L., Garcon, R., et al. 1989. The
absorption and Disposition of o carbon 14-DPX-E9636 in the Rat: Lab
Project Number: HRC/DPT 190/891138: AMR-1197-88. Unpublished study
prepared by Huntingdon Research Centre Ltd. 76p. As cited in Ref. 2.
6. Edwards, D.F. 1979. Acute Skin Absorption Test on Rabbits--
LD50: Haskell Laboratory Report No. 415-79. (Unpublished
study received Sep 1, 1981 under 352-EX-109; submitted by E.I. du
Pont de Nemours & Co., Inc., Wilmington, DE; CDL:245879-I). As cited
in Ref. 2.
7. Ferenz, R.L. 1980. LC50-Inhalation Test for
Pesticide Registration--AlbinoHaskell Laboratory Report No. 129-80.
(Unpublished study received Nov 13, 1981 under 352-404; submitted by
E.I. du Pont de Nemours & Co., Inc., Wilmington, DE; CDL:070471-H).
As cited in Ref. 2.
8. Trivits, R.L. 1979. Oral LD50 Test in Fasted Male
and Female Rats; Report No. 399-79. Unpublished study received Jun
16, 1980 under 352-EX-105; submitted by E.I. du Pont de Nemours &
Co., Inc., Wilmington, DE; CDL:099460-A). As cited in Ref. 2.
9. Smith, L.W., Kaplan, A.M., Gibson, J.R. et al. 1980. Ninety-
Day Range-Finding Feeding Study with 2-Chloro-N-o(4-methoxy-6-
methyl-1,3,5-triazin-2-yl)amino carbonyl benzenesulfonamide (INW-
4189) in Mice: Report No. 69-80. (Unpublished study including
pathology report no. 55-78, received Jun 16, 1980 under 352-EX-105l
submitted by E.I. du Pont de Nemours & Co., Wilmington, DE; CDL:
099461-B). As cited in Ref. 2.
10. Schneider, P.W., Jr., Smith, L.W., Barnes, J.R., et al.
1980. Six-Month Feeding Study in Dogs with 2-Chloro-N-o(4-methoxy-6-
methy-1,3,5-triazin-2yl)amino carbonyl benzenesulfonamide (INW-
4189): Report No. 108-80. Final rept. (Unpublished study including
pathology report no. 53-79, received Jun 16, 1980 under 352-EX-105;
submitted by E.I. du Pont de Nemours & Co., Wilmington, DE;
CDL:099461-A). As cited in Ref. 2.
11. Wood, C.K., Wollenberg, E.J., Turner, D.T., et al. 1981a.
Long-Term Feeding Study with 2-chloro-N-6(4-methoxy-6-methyl-1,3,5-
triazin-2-yl)amin ocarbonylbenzenesulfonamide (INW-4189) in Rats.
E.I. du Pont de Nemours & Company, Haskell Laboratory Report No.
557-81, November 13, 1981. MRID 0086003. Unpublished. As cited in
12. Wood, C.K., Wollenberg, E.J., Turner, D.T., et al. 1981b.
Long-Term Feeding Study with INW-4189 in Mice. E.I. du Pont de
Nemours & Company, Haskell Laboratory Report No. 836-81, December
28, 1981. MRID 0090030. Unpublished. As cited in Ref. 2.
13. Hoberman, A.M. 1980. Teratology Study in Rabbits. E.I. du
Pont de Nemours & Company, Haskell Laboratory, Newark, DE, Report
No. HLO 534-80, July 17, 1980. Unpublished. As cited in 59 FR 1788,
January 12, 1994.
14. U.S. EPA. 1998. Health Effects Test Guidelines OPPTS
870.3800 Reproduction and Fertility Effects. Washington, DC. EPA
15. Alvarez, L. 1991a. Teratogenicity Study of DPX-W4189
(Chlorsulfuron) in Rabbits. E.I. du Pont de Nemours & Company,
Haskell Laboratory for Toxicology and Industrial Medicine, Newark,
DE, Laboratory Project ID: 306-390, August 12, 1991. Unpublished. As
cited in Ref. 2.
16. Alvarez, L. 1991b. Teratogenicity Study of DPX-W4189
(Chlorsulfuron) in Rats. E.I. du Pont de Nemours & Company, Haskell
Laboratory for Toxicology and Industrial Medicine, Newark, DE,
Laboratory Project ID: 734-90, February 27, 1991. Unpublished. As
cited in Ref. 2.
17. U.S. EPA. 1991. Guidelines for Developmental Toxicity Risk
Assessment. Risk Assessment Forum, Washington, DC. EPA/600/FR-91/
18. Atkinson, J. 1991. A Chronic (1 Year) Oral Toxicity Study in
the Dog with DPX-W4189 (Chlorsulfuron) via the Diet: Lab Project
Number: 89/3501: 163/91. Unpublished study prepared by Bio/dynamics,
Inc. 716 p. As cited in Ref. 2.
19. Mylchreest, E. 2005. Chlorsulfuron (DPX-W4189) Technical:
Multigeneration Reproduction Study in Rats. DuPont Haskell
Laboratory for Health and Environmental Sciences, Newark, DE,
Laboratory Project ID: DUPONT.13495,14601,904. September 11, 2003-
June 4, 2004. MRID 46493201. Unpublished. As cited in Ref. 4. Data
Evaluation Record: Taylor, Linda (2007), MRID 46493201.
20. Rudaya, P.L., and Zhminko, P.G. 2009. Toxic Properties of
Chlorsulfuron Potassium Salt Herbicide Administered Once Orally to
Mammals. Modern Problems of Toxicology 2: 59-65. Translated from
21. Rudaya, P.L., Zhminko, P.G., Povyakel, L.I., and Reshavska,
O.V. 2010. Toxicodynamics of Chlorsulfuron Potassium Salt Given
Orally In Long-Term Experiment on White Rats. Modern Problems of
Toxicology 1: 59-63. Translated from Ukrainian.
22. Rakitsky, V.N. and Beloyedova, N.S. 2009. Toxicity and
Hazardousness of Sulfonylurea Herbicides. Toxicology Herald 4: 25-
30. Translated from Russian.
23. Dietrich, R. and McAleer, N. (1989) Hydrolysis of Phenyl(U)-
C\14\-Chlorsulfuron and Triazine-2-C\14\-Chlorsulfuron: Lab Project
Number: AMR-1455-89. 161-1. Unpublished study prepared by E.I. du
Pont de Nemours & Co., Inc. 61 pp. MRID: 42156701. As cited in Ref.
24. Hawkins, D., Kirkpatrick, D., Dean, G., et al. (1990) The
Photodegradation of C\14\-
Chlorsulfuron on a Silty Clay Loam Soil: Lab Project Number: HRC/DPT
205/90571: AMR-1563-89. Unpublished study prepared by Huntingdon
Research Centre Ltd. 58 pp. MRID: 42156703. As cited in Ref. 3.
25. Pierson, K. (1991) Flow-Through 77 Day Toxicity of DPX-
W4189-170 to Embryo and Larval Rainbow Trout, Oncorhynchus mykiss.
Lab Project Number 494-91: MR-4581-866. Unpublished study prepared
by E.I. du Pont de Nemours and Co. 471 pp. MRID: 41976405. As cited
in Ref. 3.
26. Hutton, D. (1991) Chronic Toxicity of DPX-W4189-94 to
Daphnia magna. Lab Project Number: 4581-655: 87-89. Unpublished
study prepared by E.I. du Pont de Nemours and Co. 92 pp. MRID:
41976408. As cited in Ref. 3.
27. Boeri, R., Wyskiel, D., Ward, T. (2002) Chlorsulfuron (DPX-
W4189) Technical: Influence on Growth and Growth Rate of the
Duckweed, Lemna gibba: Lab Project Number: 2042-DU: DUPONT-4468:
ASTM E1415-91. Unpublished study prepared by T.R. Wilbury
Laboratories. 38 pp. MRID: 45832901. As cited in Refs. 3 and 28.
28. Bryan, R., Worcester, D., Brichfield, N., Ballaff, D.
(2003a) Data Evaluation Report on the acute toxicity of
Chlorsulfuron to aquatic vascular plants Lemna gibba. 12 pp. MRID:
29. Blasberg, J., Hicks, S., Stratton, J. (1991) Acute Toxicity
of Chlorsulfuron to Selenastrum capricornutum Printz,: Final Report:
Lab Project Number: AMR-2081-91: 39427. Unpublished study prepared
by ABC Laboratories, Inc., 33 pp. MRID: 42186801. As cited in Ref.
30. Levy, B., Myers, T., Behl, E., Ballaff, D. (2003) Data
Evaluation Report on the acute toxicity of Chlorsulfuron to algae
Selenastrum capricornutum Printz. 12 pp. MRID: 42186801.
31. Boeri, R., Wyskiel, D., Ward, T. (2001b) Chlorsulfuron (DPX-
W4189) Technical: Influence on Growth and Growth Rate of the Alga,
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Unpublished study prepared by T.R. Wilbury Laboratories. 38 pp.
MRID: 45832903. As cited in Refs. 3 and 32.
32. Bryan, R., Worcester, D., Brichfield, N., Ballaff, D.
(2003b) Data Evaluation Report on the acute toxicity of
Chlorsulfuron to the freshwater algae Anabaena flos-aquae. 14 pp.
33. Hinkle, S. (1979) Final Report--Avian Dietary Toxicity
(LC50) Study in Bobwhite Quail: Project No. 201-523
(Unpublished study received June 16, 1980 under 352-105; prepared by
Hazelton Laboratories America, Inc., submitted by E.I. du Pont de
Nemours & Co., Wilmington, DE; CDL:099462-K). MRID: 00035265. As
cited in Ref. 3.
34. Beavers, J., Foster, J., Lynn, S. et al. (1992) H-18,053
(Chlorsulfuron): A One-generation Reproduction Study with the
Northern Bobwhite (Colinus virginianus): Lab Project Number: 112-
266: 564-92. Unpublished study prepared by Wildlife International
Ltd. 185 pp. MRID: 42634001. As cited in Ref. 3.
35. Porch, J. and Martin, K. (2004a) Chlorsulfuron (DPX-W4189)
75WG: A Greenhouse to investigate the Effects on Vegetative Vigor of
Ten Terrestrial Plants Following Foliar Exposure. Project Number:
112/542, DUPONT/13552, 14901. Unpublished study prepared by Wildlife
International, Ltd.. 191 pp. MRID: 46326801. As cited in Ref. 3.
36. Porch, J. and Martin, K. (2004b) Chlorsulfuron (DPX-W4189)
75WG: A Greenhouse to investigate the Effects on Vegetative Vigor of
Ten Terrestrial Plants Following Soil Exposure. Project Number: 112/
541, 14901, 1495. Unpublished study prepared by Wildlife
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List of Subjects in 40 CFR Part 372
Environmental protection, Community right-to-know, Reporting and
recordkeeping requirements, and Toxic chemicals.
Dated: November 18, 2013.
Arnold E. Layne,
Director, Office of Information Analysis and Access.
[FR Doc. 2013-28365 Filed 12-6-13; 8:45 am]
BILLING CODE 6560-50-P