[Federal Register Volume 74, Number 149 (Wednesday, August 5, 2009)]
[Rules and Regulations]
[Pages 38924-38935]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-18698]
=======================================================================
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2008-0889; FRL-8430-2]
Amine Salts of Alkyl (C8-C24)
Benzenesulfonic Acid (Dimethylaminopropylamine, Isopropylamine, Mono-,
Di-, and Triethanolamine); Exemption from the Requirement of a
Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes an exemption from the requirement
of a tolerance for residues of amine salts of alkyl (C8-
C24) benzenesulfonic acid (dimethylaminopropylamine,
isopropylamine, mono-, di-, and triethanolamine) when used as an inert
ingredient in pesticide formulations applied to growing crops and
applied to animals. The Joint Inerts Task Force, Cluster Support Team
Number 8, submitted a petition to EPA under the Federal Food, Drug, and
Cosmetic Act (FFDCA), requesting an exemption from the requirement of a
tolerance. This regulation eliminates the need to establish a maximum
permissible level for residues of amine salts of alkyl (C8-
C24) benzenesulfonic acid (dimethylaminopropylamine,
isopropylamine, mono-, di-, and triethanolamine).
DATES: This regulation is effective August 5, 2009. Objections and
requests for hearings must be received on or before October 5, 2009,
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2008-0889. All documents in the
docket are listed in the docket index available at http://www.regulations.gov. Although listed in the index, some information is
not publicly available, e.g., Confidential Business Information (CBI)
or other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at http://www.regulations.gov, or, if only available in hard
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
305-5805.
FOR FURTHER INFORMATION CONTACT: Kerry Leifer, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 308-8811; e-mail address: [email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural
[[Page 38925]]
producer, food manufacturer, or pesticide manufacturer. Potentially
affected entities may include, but are not limited to those engaged in
the following activities:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather to
provide a guide for readers regarding entities likely to be affected by
this action. Other types of entities not listed in this unit could also
be affected. The North American Industrial Classification System
(NAICS) codes have been provided to assist you and others in
determining whether this action might apply to certain entities. If you
have any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How Can I Access Electronic Copies of this Document?
In addition to accessing electronically available documents at
http://www.regulations.gov, you may access this Federal Register
document electronically through the EPA Internet under the ``Federal
Register'' listings at http://www.epa.gov/fedrgstr. You may also access
a frequently updated electronic version of EPA's tolerance regulations
at 40 CFR part 180 through the Government Printing Office's e-CFR cite
at http://www.gpoaccess.gov/ecfr. To access the OPPTS Harmonized
Guidelines referenced in this document, go directly to the guidelines
at http://www.epa.gov/opptsfrs/home/guidelin.htm.
C. Can I File an Objection or Hearing Request?
Under section 408(g) of FFDCA, 21 U.S.C. 346a, any person may file
an objection to any aspect of this regulation and may also request a
hearing on those objections. You must file your objection or request a
hearing on this regulation in accordance with the instructions provided
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify
docket ID number EPA-HQ-OPP-2008-0889 in the subject line on the first
page of your submission. All requests must be in writing, and must be
mailed or delivered to the Hearing Clerk as required by 40 CFR part 178
on or before October 5, 2009.
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit this copy, identified by docket ID number
EPA-HQ-OPP-2008-0889, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket Facility's normal hours of operation (8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays).
Special arrangements should be made for deliveries of boxed
information. The Docket Facility telephone number is (703) 305-5805.
II. Background
In the Federal Register of March 25, 2009 (74 FR 12856) (FRL-8399-
4), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
8E7472) by The Joint Inerts Task Force (JITF), Cluster Support Team 8
(CST 8), c/o CropLife America, 1156 15th Street, NW., Suite 400,
Washington, DC 20005. The petition requested that 40 CFR 180.920 and 40
CFR 180.930 be amended by establishing exemptions from the requirement
of a tolerance for residues of the inert ingredient amine salts of
alkyl (C8-C24) benzenesulfonic acid
(dimethylaminopro-pylamine, isopropylamine, mono-, di-, and
triethanolamine) (herein referred to in this document as ASABSA)
including CAS Reg. Nos. 68953-97-9, 26545-53-9, 877677-48-0, 319926-68-
6, 90194-53-9, 55470-69-4, 68910-32-7, 26264-05-1, 157966-96-6, 68584-
24-7, 68648-81-7, 68649-00-3, 68953-93-5, 90218-35-2, 27323-41-7,
68584-25-8, 68648-96-4, 68411-31-4, 90194-42-6, and 1093628-27-3, when
used as an inert ingredient in pesticide formulations applied to
growing crops under 40 CFR 180.920 and applied to animals under 40 CFR
180.930. That notice referenced a summary of the petition prepared by
The JITF, CST 8, the petitioner, which is available to the public in
the docket, http://www.regulations.gov. There were no comments received
in response to the notice of filing.
Based upon review of the data supporting the petition, EPA has
modified the exemption requested by limiting the diethanolamine salt of
alkyl (C8-C24) benzenesulfonic acid (CAS Reg.
Nos. 26545-53-9 and 68953-97-9) to a maximum of 7% by weight in
pesticide formulations intended for application to growing crops and to
animals. This limitation is based on the Agency's risk assessment which
can be found at http://www.regulations.gov in documents
``Dimethylaminopropylamine, Isopropylamine, Ethanolamine and
Triethanolamine Salts of Alkyl (C8-C24)
Benzenesulfonic Acid (JITF CST 8 Inert Ingredients). Human Health Risk
Assessment to Support Proposed Exemption from the Requirement of a
Tolerance When Used as Inert Ingredients in Pesticide Formulations and
Diethanolamine Salt of Alkyl (C8-C24)
Benzenesulfonic Acid (DEA - JITF CST 8 Inert Ingredient). Human Health
Risk Assessment to Support Proposed Exemption from the Requirement of a
Tolerance When Used as Inert Ingredients in Pesticide Formulations,''
in docket ID number EPA-HQ-OPP-2008-0889.
This petition was submitted in response to a final rule that was
published in the Federal Register of August 9, 2006 (71 FR 45415) (FRL-
8084-1) in which the Agency revoked, under section 408(e)(1) of FFDCA,
the existing exemptions from the requirement of a tolerance for
residues of certain inert ingredients because of insufficient data to
make the determination of safety required by section 408(b)(2) of
FFDCA. The expiration date for the tolerance exemptions subject to
revocation was August 9, 2008, which was later extended to August 9,
2009 in the Federal Register of August 4, 2008 (73 FR 45317) (FRL-8373-
6) to allow for data to be submitted to support the establishment of
tolerance exemptions for these inert ingredients prior to the effective
date of the tolerance exemption revocation.
III. Inert Ingredient Definition
Inert ingredients are all ingredients that are not active
ingredients as defined in 40 CFR 153.125 and include, but are not
limited to, the following types of ingredients (except when they have a
pesticidal efficacy of their own): Solvents such as alcohols and
hydrocarbons; surfactants such as polyoxyethylene polymers and fatty
acids; carriers such as clay and diatomaceous earth; thickeners such as
carrageenan and modified cellulose;
[[Page 38926]]
wetting, spreading, and dispersing agents; propellants in aerosol
dispensers; microencapsulating agents; and emulsifiers. The term
``inert'' is not intended to imply nontoxicity; the ingredient may or
may not be chemically active. Generally, EPA has exempted inert
ingredients from the requirement of a tolerance based on the low
toxicity of the individual inert ingredients.
IV. Aggregate Risk Assessment and Determination of Safety
Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish an
exemption from the requirement of a tolerance (the legal limit for a
pesticide chemical residue in or on a food) only if EPA determines that
the tolerance is ``safe.'' Section 408(b)(2)(A)(ii) of FFDCA defines
``safe'' to mean that ``there is a reasonable certainty that no harm
will result from aggregate exposure to the pesticide chemical residue,
including all anticipated dietary exposures and all other exposures for
which there is reliable information.'' This includes exposure through
drinking water and in residential settings, but does not include
occupational exposure. Section 408(b)(2)(C) of FFDCA requires EPA to
give special consideration to exposure of infants and children to the
pesticide chemical residue in establishing a tolerance and to ``ensure
that there is a reasonable certainty that no harm will result to
infants and children from aggregate exposure to the pesticide chemical
residue. * * *''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. First, EPA determines the
toxicity of pesticides. Second, EPA examines exposure to the pesticide
through food, drinking water, and through other exposures that occur as
a result of pesticide use in residential settings.
Consistent with section 408(b)(2)(D) of FFDCA, and the factors
specified in section 408(b)(2)(D) of FFDCA, EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of and to
make a determination on aggregate exposure for the petitioned-for
exemption from the requirement of a tolerance for residues of ASABSA
when used as inert ingredients in pesticide formulations applied to
growing crops and to animals. EPA's assessment of exposures and risks
associated with establishing tolerances follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children.
Amine salts of alkyl (C8-C24) benzenesulfonic
acid readily and fully dissociate to the corresponding amine and alkyl
(C8-C24) benzenesulfonic acid constituents,
therefore the hazard assessment conducted to support the requested
exemption from the requirement of a tolerance for ASABSA is primarily
based on the hazard assessment for each of the constituents,
specifically each associated amine (i.e., dimethylaminopropylamine,
isopropylamine, ethanolamine, diethanol-amine and triethanolamine) and
alkyl (C8-C24) benzenesulfonic acid.
The hazard profile and endpoints for risk assessment for
alkylbenzene sulfonic acid have previously been addressed as part of
the tolerance reassessment for tolerance exemptions for alkyl
(C8-C24) benzenesulfonic acid and its ammonium,
calcium, magnesium, potassium, sodium, and zinc salts http://www.epa.gov/opprd001/inerts/alkylc8.pdf. The toxicology database for
these alkylbenzene sulfonates consists almost entirely of published
literature, and is essentially complete and of acceptable quality to
assess the potential hazard to humans. The alkylbenzene sulfonates are
readily absorbed following oral ingestion, but not following dermal
exposure. Following oral exposure, they are readily metabolized,
excreted fairly rapidly, and do not accumulate in any tissues.
Available acute toxicity data show that alkylbenzene sulfonates are not
highly acutely toxic, are irritating to the eye and skin, and are not
skin sensitizers. Subchronic and chronic exposures show that the liver,
kidney and intestinal tract (following oral exposures) are the major
target organs of toxicity. Both in vitro and in vivo genotoxicity data
show that alkylbenzene sulfonates are not genotoxic. The alkylbenzene
sulfonates did not cause reproductive or developmental toxicity in
acceptable studies. Early (pre Good Laboratory Practice standards)
carcinogenicity studies indicate that alkylbenzene sulfonates do not
cause an increase in tumor incidence.
The existing toxicology database for the dimethylaminopropylamine,
isopropylamine, ethanolamine and triethanolamine salt of alkyl
(C8-C24) benzenesulfonic acid consists of an
OPPTS Harmonized Test Guideline 870.3550 study and acute, subchronic,
chronic, carcinogenicity, developmental, and mutagenicity studies on
the individual amines. In addition, the petitioner submitted an OPPTS
Harmonized Test Guideline 870.3650 combined repeated dose toxicity
study with the reproduction/developmental toxicity screening tests on
isopropylamine dodecylbenzene sulfonate. The Agency considered these
data in its evaluation of amine toxicity. While the test compound for
the study is effectively a mixture of the amine and the acid, the study
findings do provide some insight into the potential toxicity of the
amine constituent.
A summary of the toxicological data considered as part of this
action is given below:
1. Isopropylamine dodecylbenzene sulfonate (CAS No. 26264-05-1). In
an oral gavage OPPTS Harmonized Test Guideline 870.3650 combined
repeated dose toxicity study with the reproduction/developmental
toxicity screening tests, the parental LOAEL was 320 milligrams/
kilograms/day (mg/kg/day) (highest dose tested, (HDT)) based on
excessive salivation (both sexes), soft/liquid feces (males), lesions
of the forestomach (both sexes). No reproductive or developmental
toxicity or neurotoxicity was observed. The NOAEL was 80 mg/kg/day.
2. Ethanolamine (CAS No. 141-43-5). Ethanolamine is not acutely
toxic in rats by the oral route of exposure but appears to be very
acutely toxic by the dermal route of exposure, although this may be a
species-specific effect in the rabbit. It is a skin sensitizer and is
corrosive to the eye and skin. There is no evidence of mutagenicity in
the Ames, Saccharomyces cerevisiae gene conversion, mouse micronucleus,
cell transformation, and SCE human lymphocytes tests. In a dermal rat
developmental toxicity study conducted with ethanolamine, no maternal
or developmental toxicity was observed at 225 mg/kg/day (HDT). Also in
a dermal rabbit developmental toxicity study, no maternal or
developmental toxicity was observed at 75 mg/kg/day (HDT). In an oral
rat developmental toxicity study, the maternal LOAEL was 450 mg/kg/day
(HDT) based on decreased body weights during the latter part of
gestation and throughout lactation. The developmental LOAEL was 450 mg/
kg/day based on decrease body weights in female fetuses on postnatal
day (PND) 1 and 4. The maternal/developmental NOAEL was 120 mg/kg/day.
3. Triethanolamine (CAS No. 102-71-6). In acute toxicity studies,
triethanolamine is mildly to moderately toxic by the oral and dermal
routes of
[[Page 38927]]
exposure. It is not irritating in eye and skin irritation studies, and
it is not a skin sensitizer. There is no evidence of mutagenicity in
the Ames, mouse micronucleus, sex-linked recessive lethal, and Chinese
hamster ovary (CHO) cell cytogenetics tests. In a 14-day inhalation
study in rat, the NOAEL was 0.25 milligram/liter (mg/L) (approximate
oral equivalent dose of 75 mg/kg/day) and the LOAEL was 0.5 mg/L based
on increased kidney weights of males and females. In an oral mouse
developmental toxicity study (Chernoff-Kavlock screening test), no
maternal or developmental toxicity was observed at 1,125 mg/kg/day
(only dose tested). In a 13-week dermal study in rat, the NOAEL was
1,000 mg/kg/day and the LOAEL was 2,000 mg/kg/day (HDT) based on
reduced body gain and clinical observations (irritation, scaliness, and
crustiness of the skin at the site of application). In a 13-week dermal
study in mouse, the NOAEL was 2,000 mg/kg/day and the LOAEL was 4,000
mg/kg/day (HDT) based on clinical observations (irritation, scaliness,
and discoloration of the skin at the site of application).
4. Isopropylamine (CAS No. 75-31-0). In acute toxicity studies,
isopropylamine is moderately acutely toxic in rats by the oral route of
exposure, but is less toxic by the dermal route and is not toxic by the
inhalation route of exposure. Rabbits appear to be more sensitive than
rats showing significantly greater acute toxicity by the dermal route.
Isopropylamine is not a skin sensitizer. There is no evidence of
mutagenicity in the Ames, chromosomal aberrations in human lymphocytes
and unscheduled DNA synthesis in rat hepatocytes tests. In a 28-day
inhalation study, Sprague-Dawley rats were exposed to inhalation dosage
levels of 0, 0.1, 0.5, and 1.35 mg/L for 6 hours/day for 5 days/week.
The NOAEL was 0.1 mg/L and the LOAEL was 0.5 mg/L based on microscopic
ocular and nasal lesions. In a developmental study, Sprague-Dawley rats
were exposed to inhalation dosage levels of 0, 0.1, 0.5, and 1.0 mg/L
for 6 hours/day from gestation day (GD) 6 through 15. The maternal
toxicity was observed at 1.0 mg/L (HDT) based on decreased body weight
and body weight gain. At this dose, no developmental toxicity was
observed.
5. Dimethylaminopropylamine (CAS No. 109-55-7).
Dimethylaminopropylamine is mild to moderately toxic by the oral and
inhalation routes of exposure, but it is not a skin sensitizer. There
is no evidence of mutagenicity in the Ames and mouse micronucleus
tests. Following a 28-day gavage study in Wistar rats, mortality (4/5
females) and clinical signs (males: irregular respiration and
respiratory sounds; females: decreased spontaneous activity, stilted
gait, swollen abdomen, and impaired respiration) were observed at 250
mg/kg/day (HDT). In an OPPTS Harmonized Test Guideline 870.3550
reproduction and developmental toxicity screening test in Sprague-
Dawley rats, parental toxicity was observed at 200 mg/kg/day (HDT)
based on decreased body weight gain and clinical signs (respiratory
sounds and piloerection). Reproductive and developmental toxicity were
not observed at any dose level.
6. Diethanolamine (CAS No. 11-42-2). The existing toxicology
database for diethanolamine (DEA) consists of several subchronic oral
and dermal toxicity studies in rats and mice, carcinogenicity studies
in rats and mice, oral and dermal developmental toxicity studies in
rats and rabbits, and acute and mutagenicity data. Following repeat
oral exposure to DEA, the kidney, liver, and blood are the major target
organs. Repeat oral exposure via drinking water resulted in a
microcytic anemia that does not involve the bone marrow in rats at 97
mg/kg/day in males and 57 mg/kg/day in females. Increased kidney
weights were associated with renal tubular cell necrosis, decreased
renal function, increased incidences or severity of nephropathy, and/or
mineralization in rats at 97 mg/kg/day (males) and 57 mg/kg/day
(females) and in mice at 104 mg/kg/day (lowest dose tested, (LDT)) in
males and 142 mg/kg/day (LDT) in females. Increased liver weights were
associated with cytoplasmic vacuolization and degeneration of
centrilobular hepatocytes in rats and hypertrophy, individual cell
necrosis or foci of necrotic hepatocytes in mice. Dose-related
decreases in testis and epididymis weights were associated with
testicular degeneration, decreased sperm motility, and decreased sperm
count in male rats at 97 mg/kg/day. Similar kidney and liver effects
were observed following repeat dermal exposure at dose levels of 32/mg/
kg/day in rats and 80 mg/kg/day in mice. Demyelination in the brain
(medulla oblongata) and spinal cord was observed in rats of both sexes
following oral and dermal exposure at dose levels as low as 250 mg/kg/
day, with the female being more sensitive. Mortality and neurological
symptoms (tremors, stiffness, and ataxia progressing to paresis and
paralysis) have been reported following exposure via over-the-counter
oral flea treatment (53% DEA) of dogs and cats, however, there are no
registered pet care use products containing the DEA salt form of
ASABSA.
Developmental toxicity was observed in rats following both oral and
dermal exposure to the maternal animal during gestation days (GD) 6-15.
Maternal toxicity, as evidenced by decreased body weight/gain and food
consumption and/or increased kidney weight, was observed at the same
dose levels (125 mg/kg/day) as the developmental effects [an increase
in postnatal mortality (PND 0 through 4), an increase in
postimplantation loss, and reduced pup body weight following oral
exposure. An increased incidence of skeletal variations was observed
following dermal exposure at 1500 mg/kg/day (HDT) ]. Developmental
toxicity was not observed in rabbits following oral or dermal exposure
of the maternal animal during GD 6 through 18.
7. Metabolism. The alkyl (C8-C24)
benzenesulfonic acid amine salts undergo rapid dissociation in vivo to
form an alkyl (C8-C24) benzenesulfonic acid and
an amine. The two entities would be absorbed and metabolized
independently. The alkyl (C8-C24) benzenesulfonic
acid should be readily conjugated and rapidly excreted with little
alkyl aromatic chain degradation (JITF Submission, 2008, pages 11 and
21). Primary, secondary or tertiary amines should undergo oxidative
amine metabolism followed by excretion. Primary aliphatic amines
(ethanolamine, isopropylamine) are oxidized to aldehydes/ketones and or
acid (glycolic acid or acetone) with release of ammonia. The glycolic
acid may further oxidized and or conjugated and excreted. The acetone
could be excreted through respiration or further oxidized to
methylglyoxyl and then excreted. Secondary aliphatic amines
(dimethylaminopropylamine and diethanolamine) may follow various
oxidative patterns and some are excreted unchanged. Small molecular
weight amines may be exhaled via respiration. Tertiary aliphatic amines
(triethanolamine) may be oxidized to amine oxides, which may be
excreted in the urine or deaminated with the eventual resultant being
release of glycolic acid which may be further oxidized and or
conjugated and excreted.
Specific information on the studies received and the nature of the
adverse effects caused by ASABSA and its constituents as well as the
no-observed-adverse-effect-level (NOAEL) and the lowest-observed-
adverse-effect-level (LOAEL) from the toxicity studies can
[[Page 38928]]
be found at http://www.regulations.gov in documents
``Dimethylaminopropylamine, Isopropylamine, Ethanolamine and
Triethanolamine Salts of Alkyl (C8-C24)
Benzenesulfonic Acid (JITF CST 8 Inert Ingredients). Human Health Risk
Assessment to Support Proposed Exemption from the Requirement of a
Tolerance When Used as Inert Ingredients in Pesticide Formulations and
Diethanolamine Salt of Alkyl (C8-C24)
Benzenesulfonic Acid (DEA - JITF CST 8 Inert Ingredient). Human Health
Risk Assessment to Support Proposed Exemption from the Requirement of a
Tolerance When Used as Inert Ingredients in Pesticide Formulations,''
in docket ID number EPA-HQ-OPP-2008-0889 and at http://www.epa.gov/opprd001/inerts/alkylc8.pdf.
B. Toxicological Endpoints
For hazards that have a threshold below which there is no
appreciable risk, a toxicological point of departure (POD) is
identified as the basis for derivation of reference values for risk
assessment. The POD may be defined as the highest dose at which no
adverse effects are observed (the NOAEL) in the toxicology study
identified as appropriate for use in risk assessment. However, if a
NOAEL cannot be determined, the lowest dose at which adverse effects of
concern are identified (the LOAEL) or a Benchmark Dose (BMD) approach
is sometimes used for risk assessment. Uncertainty/safety factors (UFs)
are used in conjunction with the POD to take into account uncertainties
inherent in the extrapolation from laboratory animal data to humans and
in the variations in sensitivity among members of the human population
as well as other unknowns. Safety is assessed for acute and chronic
dietary risks by comparing aggregate food and water exposure to the
pesticide to the acute population adjusted dose (aPAD) and chronic
population adjusted dose (cPAD). The aPAD and cPAD are calculated by
dividing the POD by all applicable UFs. Aggregate short-, intermediate-
, and chronic-term risks are evaluated by comparing food, water, and
residential exposure to the POD to ensure that the margin of exposure
(MOE) called for by the product of all applicable UFs is not exceeded.
This latter value is referred to as the Level of Concern (LOC).
For non-threshold risks, the Agency assumes that any amount of
exposure will lead to some degree of risk. Thus, the Agency estimates
risk in terms of the probability of an occurrence of the adverse effect
greater than that expected in a lifetime. For more information on the
general principles EPA uses in risk characterization and a complete
description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.
A summary of the toxicological endpoints for ASABSA used for human
health risk is shown in the following Table 1.
Table 1.--Summary of Toxicological Doses and Endpoints for ASABSA for Use in Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
Point of Departure and
Exposure/Scenario Uncertainty/Safety RfD, PAD, LOC for Risk Study and Toxicological
Factors Assessment Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary (all populations) An effect attributable to a single exposure was not identified.
----------------------------------------------------------------------------------------------------------------
Chronic dietary (all populations) NOAEL = 50 mg/kg/day Chronic RfD = 0.5 mg/ 28-day oral (gavage)
dimethylaminopropylamine, UFA = 10x............. kg/day toxicity study in rats
isopropylamine, ethanolamine, and UFH = 10x............. cPAD = 0.5 mg/kg/day.. with
triethanolamine salts of alkyl (C8- FQPA SF = 1x.......... dimethylaminopropylamine
C24) benzenesulfonic acid. NOAEL = 50 mg/kg
LOAEL = 250 mg/kg based on
mortality (4/5 females)
and clinical signs (males:
irregular respiration and
respiratory sounds;
females: decreased
spontaneous activity,
stilted gait, swollen
abdomen, impaired
respiration) OECD SIDS.
UNEP Publication and BUA
Report, October 1996 plus
weight of evidence of
three studies with
alkylbenzene sulfonates:
1) Rat reproduction study
LOAEL = 250 mg/kg/day
based on decreased Day 21
female pup body weight
(Buehler, E. et al. 1971.
Tox. Appl. Pharmacol.18:83-
91)
2) 9-month drinking water
rat study
LOAEL = 145 mg/kg/day based
on decreased body weight
gain, and serum/
biochemical and enzymatic
changes in the liver
andkidney (Yoneyama et al.
1976 Ann. Rep. Tokyo
Metrop. Res.Lab. Public
Health 27(2):105-112)
3) 6-month rat dietary
study
LOAEL = 114 mg/kg/day
(0.2%) based on increased
caecum weight and slight
kidney damage (Yoneyama et
al 1972 Ann. Rep. Tokyo
Metrop. Res. Lab. Public
Health 24:409-440)
----------------------------------------------------------------------------------------------------------------
[[Page 38929]]
Chronic dietary (all populations) NOAEL = 48 mg/kg/day Chronic RfD = 0.5 mg/ Subchronic (13-week) oral
diethanolamine salt of alkyl (C8- UFA = 10x............. kg/day toxicity study in rats
C24) benzenesulfonic acid UFH = 10x............. cPAD = 0.05 mg/kg/day. (NTP, 1992)
FQPA SF = 10x......... Female LOAEL = 124 mg/kg/
day demyelination of the
brain and spinal cord
Male LOAEL = 97 mg/kg/day,
based on decreased testis
and epididymis weight
associated with
degeneration of
seminiferous epithelium,
decreased numbers of
spermatogenic cells,
reduced size of
seminiferous tubules,
decreased sperm, sperm
motility, and sperm count
----------------------------------------------------------------------------------------------------------------
Incidental Oral and Inhalation NOAEL = 50 mg/kg/day Residential LOC for 28-day oral (gavage)
short-term (1 to 30 days) and UFA = 10x............. MOE = 100 toxicity study in rats
intermediate-term (1 to 6 months) UFH = 10x............. with
dimethylaminopropylamine, FQPA SF = 1x.......... dimethylaminopropylamine
isopropylamine, ethanolamine, and inhalation toxicity is NOAEL = 50 mg/kg
triethanolamine salts of alkyl (C8- assumed to be LOAEL = 250 mg/kg based on
C24) benzenesulfonic acid. equivalent to oral mortality (4/5 females)
toxicity. and clinical signs (males:
irregular respiration and
respiratory sounds;
females: decreased
spontaneous activity,
stilted gait, swollen
abdomen, impaired
respiration) OECD SIDS.
UNEP Publication and BUA
Report, October 1996 plus
weight of evidence of
three studies with
alkylbenzene sulfonates:
1) Rat reproduction study
LOAEL = 250 mg/kg/day
based on decreased Day 21
female pup body weight
(Buehler, E. et al. 1971.
Tox. Appl. Pharmacol.18:83-
91)
2) 9-month drinking water
rat study LOAEL = 145 mg/
kg/day based on decreased
body weight gain, and
serum/ biochemical and
enzymatic changes in the
liver andkidney (Yoneyama
et al. 1976 Ann. Rep.
Tokyo Metrop. Res. Lab.
Public Health 27(2):105-
112)
3) 6-month rat dietary
study LOAEL = 114 mg/kg/
day (0.2%) based on
increased caecum weight
and slight kidney damage
(Yoneyama et al 1972 Ann.
Rep. Tokyo Metrop. Res.
Lab. Public Health 24:409-
440)
----------------------------------------------------------------------------------------------------------------
Incidental Oral and Inhalation NOAEL = 48 mg/kg/day Residential LOC for Subchronic (13-week) oral
short-term (1 to 30 days) and UFA = 10x............. MOE = 1,000 toxicity study in rats
intermediate-term (1 to 6 months)-- UFH = 10x............. (NTP, 1992)
diethanolamine salt of alkyl (C8- FQPA SF = 10x......... Female LOAEL = 124 mg/kg/
C24) benzenesulfonic acid. inhalation toxicity is day based on demyelination
assumed to be of the brain and spinal
equivalent to oral cord
toxicity. Male LOAEL = 97 mg/kg/day,
based on decreased testis
and epididymis weight
associated with
degeneration of
seminiferous epithelium,
decreased numbers of
spermatogenic cells,
reduced size of
seminiferous tubules,
decreased sperm, sperm
motility, and sperm count
----------------------------------------------------------------------------------------------------------------
Dermal (short- and intermediate- No systemic toxicity observed in available dermal toxicity study. Low
term) -- dimethylaminopropylamine, potential for dermal absorption to ionized amine. No quantitative risk
isopropylamine, ethanolamine, and assessment required
triethanolamine salts of alkyl (C8-
C24) benzenesulfonic acid.
----------------------------------------------------------------------------------------------------------------
Dermal (short- and intermediate- NOAEL = 125 mg/kg/day Residential LOC for
term) -- diethanolamine salt of UFA = 10x............. MOE = 1,000
alkyl (C8-C24) benzenesulfonic UFH = 10x.............
acid FQPA SF = 10x.........
----------------------------------------------------------------------------------------------------------------
[[Page 38930]]
Cancer (oral, dermal, inhalation) Classification: Based on SAR analysis, ASABSA is not expected to be
carcinogenic. No evidence of carcinogenicity in the available data or SAR
analysis for alkyl benzenesulfonates, dimethylaminopropylamine,
isopropylamine, ethanolamine, and triethanolamine. No concern for
diethanolamine based on SAR analysis, limited evidence in experimental
animals; not classifiable as to its carcinogenicity to humans
----------------------------------------------------------------------------------------------------------------
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data
and used to mark the beginning of extrapolation to determine risk associated with lower environmentally
relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect
level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential
variation in sensitivity among members of the human population (intraspecies). PAD = population adjusted dose
(a=acute, c=chronic). FQPA SF = FQPA Safety Factor. RfD = reference dose. MOE = margin of exposure. LOC =
level of concern. N/A = not applicable.
C. Exposure Assessment
Very limited information is available for ASABSA with respect to
plant and animal metabolism or environmental degradation. The Agency
relied collectively on information provided on the representative
chemical structures, the generic cluster structures, the modeled
physicochemical information, as well as the structure-activity
relationship information. Additionally, information on other
surfactants and chemicals of similar size and functionality was
considered to determine the residues of concern for these inert
ingredients. ASABSA are likely to be fully dissociated in solution. If
dissociated amine counter ion or alkylbenzenesulfonic acid residues on
plants and livestock undergo any metabolism or hydrolysis, they will
likely result as highly polar or conjugated residues, which would not
be of concern.
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to ASABSA, EPA considered exposure under the petitioned-for
exemptions from the requirement of a tolerance. EPA assessed dietary
exposures from ASABSA in food as follows:
i. Acute exposure. No adverse effects attributable to a single
exposure of ASABSA were seen in the toxicity databases. Therefore, an
acute dietary risk assessment for ASABSA is not necessary.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment for ASABSA, EPA used food consumption information from the
U.S. Department of Agriculture (USDA) 1994-1996 and 1998 Nationwide
Continuing Surveys of Food Intake by Individuals (CSFII). As to residue
levels in food, no residue data were submitted for ASABSA. In the
absence of specific residue data, EPA has developed an approach which
uses surrogate information to derive upper bound exposure estimates for
the subject inert ingredient. Upper bound exposure estimates are based
on the highest tolerance for a given commodity from a list of high-use
insecticides, herbicides, and fungicides. A complete description of the
general approach taken to assess inert ingredient risks in the absence
of residue data can be found at http://www.regulations.gov in the
document ``Alkyl Amines Polyalkoxylates (Cluster 4): Acute and Chronic
Aggregate (Food and Drinking Water) Dietary Exposure and Risk
Assessments for the Inerts'', in docket ID number EPA-HQ-OPP-2008-0738.
In the dietary exposure assessment, the Agency assumed that the
residue level of the inert ingredient would be no higher than the
highest tolerance for a given commodity. Implicit in this assumption is
that there would be similar rates of degradation (if any) between the
active and inert ingredient and that the concentration of inert
ingredient in the scenarios leading to these highest of tolerances
would be no higher than the concentration of the active ingredient.
The Agency believes the assumptions used to estimate dietary
exposures lead to an extremely conservative assessment of dietary risk
due to a series of compounded conservatisms. First, assuming that the
level of residue for an inert ingredient is equal to the level of
residue for the active ingredient will overstate exposure. The
concentrations of active ingredient in agricultural products are
generally at least 50 percent of the product and often can be much
higher. Further, pesticide products rarely have a single inert
ingredient; rather there is generally a combination of different inert
ingredients used which additionally reduces the concentration of any
single inert ingredient in the pesticide product relative to that of
the active ingredient. EPA made a specific adjustment to the dietary
exposure assessment to account for the use limitations of the amount of
diethanolamine salts of alkyl (C8-C24)
benzenesulfonic acid that may be in formulations (no more than 7%,
which corresponds to a concentration of 2% diethanolamine) and assumed
that the diethanolamine salts of alkyl (C8-C24)
benzenesulfonic acid are at the maximum limitations rather than at
equal quantities with the active ingredient. This remains a very
conservative assumption because surfactants are generally used at
levels far below these percentages. For example, EPA examined several
of the pesticide products associated with the tolerance/commodity
combination which are the driver of the risk assessment and found that
these products did not contain surfactants at levels greater than 2.25%
and that none of the surfactants were diethanolamine salts of alkyl
(C8-C24) benzenesulfonic acid.
Second, the conservatism of this methodology is compounded by EPA's
decision to assume that, for each commodity, the active ingredient
which will serve as a guide to the potential level of inert ingredient
residues is the active ingredient with the highest tolerance level.
This assumption overstates residue values because it would be highly
unlikely, given the high number of inert ingredients, that a single
inert ingredient or class of ingredients would be present at the level
of the active ingredient in the highest tolerance for every commodity.
Finally, a third compounding conservatism is EPA's assumption that all
foods contain the inert ingredient at the highest tolerance level. In
other words, EPA assumed 100 percent of all foods are treated with the
inert ingredient at the rate and manner necessary to produce the
highest residue legally possible for an active ingredient.
[[Page 38931]]
In summary, EPA chose a very conservative method for estimating what
level of inert residue could be on food, and then used this methodology
to choose the highest possible residue that could be found on food and
assumed that all food contained this residue. No consideration was
given to potential degradation between harvest and consumption even
though monitoring data shows that tolerance level residues are
typically one to two orders of magnitude higher than actual residues in
food when distributed in commerce.
Accordingly, although sufficient information to quantify actual
residue levels in food is not available, the compounding of these
conservative assumptions will lead to a significant exaggeration of
actual exposures. EPA does not believe that this approach
underestimates exposure in the absence of residue data.
iii. Cancer. The Agency used a qualitative structure activity
relationship (SAR) database, DEREK11, to determine if there were
structural alerts suggestive of carcinogenicity. No structural alerts
for carcinogenicity were identified. Additionally, there is not
evidence of carcinogenicity of the ASABSA amine or alkylbenzenesulfonic
acid constituents. Therefore, a cancer dietary exposure assessment is
not necessary to assess cancer risk.
iv. Anticipated residue and percent crop treated (PCT) information.
EPA did not use anticipated residue and/or PCT information in the
dietary assessment for ASABSA. Tolerance level residues and/or 100%
crop treated were assumed for all food commodities.
2. Dietary exposure from drinking water. The Agency used screening
level water exposure models in the dietary exposure analysis and risk
assessment for ASABSA in drinking water. These simulation models take
into account data on the physical, chemical, and fate/transport
characteristics of ASABSA. Further information regarding EPA drinking
water models used in the pesticide exposure assessment can be found at
http://www.epa.gov/oppefed1/models/water/index.htm.
A screening level drinking water analysis, based on the Pesticide
Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS) was
performed to calculate the estimated drinking water concentrations
(EDWCs) of ASABSA. Modeling runs on four surrogate inert ingredients
using a range of physical chemical properties that would bracket those
of ASABSA were conducted. Modeled acute drinking water values ranged
from 0.001 parts per billion (ppb) to 41 ppb. Modeled chronic drinking
water values ranged from 0.0002 ppb to 19 ppb. Further details of this
drinking water analysis can be found at http://www.regulations.gov in
the documents ``Dimethylaminopropylamine, Isopropylamine, Ethanolamine
and Triethanolamine Salts of Alkyl (C8-C24)
Benzenesulfonic Acid (JITF CST 8 Inert Ingredients). Human Health Risk
Assessment to Support Proposed Exemption from the Requirement of a
Tolerance When Used as Inert Ingredients in Pesticide Formulations and
Diethanolamine Salt of Alkyl (C8-C24)
Benzenesulfonic Acid (DEA - JITF CST 8 Inert Ingredient). Human Health
Risk Assessment to Support Proposed Exemption from the Requirement of a
Tolerance When Used as Inert Ingredients in Pesticide Formulations,''
in docket ID number EPA-HQ-OPP-2008-0889.
For the purpose of the screening level dietary risk assessment to
support this request for an exemption from the requirement of a
tolerance for ASABSA, a conservative drinking water concentration value
of 100 ppb based on screening level modeling was used to assess the
contribution to drinking water for chronic dietary risk assessments for
the parent compounds and for the metabolites of concern. These values
were directly entered into the dietary exposure model.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets). ASABSA may be used as
inert ingredients in pesticide products that are registered for
specific uses that may result in outdoor residential exposures. A
screening level residential exposure and risk assessment was completed
for pesticide products containing ASABSA as inert ingredients. In this
assessment, representative scenarios, based on end-use product
application methods and labeled application rates, were selected. For
each of the use scenarios, the Agency assessed residential handler
(applicator) inhalation and dermal exposure for use scenarios with high
exposure potential (i.e., exposure scenarios with high-end unit
exposure values) to serve as a screening assessment for all potential
residential pesticides containing ASABSA. Similarly, residential
postapplication dermal and oral exposure assessments were also
performed utilizing high-end exposure scenarios. Further details of
this residential exposure and risk analysis can be found at http://www.regulations.gov in the document ``JITF Inert Ingredients.
Residential and Occupational Exposure Assessment Algorithms and
Assumptions Appendix for the Human Health Risk Assessments to Support
Proposed Exemption from the Requirement of a Tolerance When Used as
Inert Ingredients in Pesticide Formulations,'' in docket ID number EPA-
HQ-OPP-2008-0710.
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
EPA has not found ASABSA to share a common mechanism of toxicity
with any other substances, and ASABSA do not appear to produce a toxic
metabolite produced by other substances. For the purposes of this
tolerance action, therefore, EPA has assumed that ASABSA do not have a
common mechanism of toxicity with other substances. For information
regarding EPA's efforts to determine which chemicals have a common
mechanism of toxicity and to evaluate the cumulative effects of such
chemicals, see EPA's website at http://www.epa.gov/pesticides/cumulative.
D. Safety Factor for Infants and Children
1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA
shall apply an additional tenfold (10X) margin of safety for infants
and children in the case of threshold effects to account for prenatal
and postnatal toxicity and the completeness of the database on toxicity
and exposure unless EPA determines based on reliable data that a
different margin of safety will be safe for infants and children. This
additional margin of safety is commonly referred to as the FQPA safety
factor (SF). In applying this provision, EPA either retains the default
value of 10X, or uses a different additional safety factor when
reliable data available to EPA support the choice of a different
factor.
2. Prenatal and postnatal sensitivity.--i. Dimethylaminopro-
pylamine, isopropylamine, ethanolamine, and triethanolamine salts of
alkyl (C8-C24) benzenesulfonic acid. The
available mammalian toxicology database for dimethylaminopropylamine,
isopropylamine, ethanolamine, and triethanolamine salts of alkyl
(C8-C24) benzenesulfonic is complete with respect
to assessing the increased susceptibility to infants and
[[Page 38932]]
children as required by FQPA for the dimethylaminopropylamine,
isopropylamine, ethanolamine and triethan-olamine salts of alkyl
(C8-C24) benzenesulfonic acid. There was no
increased susceptibility to the offspring of rats following prenatal
and postnatal exposure in the OPPTS Harmonized Test Guidelines 870.3550
and 870.3650 reproductive/developmental screening studies, and
developmental effects studies.
There was no increased susceptibility to the offspring of rats
following prenatal and postnatal exposure in the OPPTS Harmonized Test
Guideline 870.3650 study with isopropylamine dodecylbenzene sulfonate.
Developmental toxicity was not observed, whereas parental toxicity was
manifested as excessive salivation in both sexes, soft feces in males,
and lesions of the forestomach in both sexes. No increased
susceptibility was observed in offspring of rats following exposure in
the OPPTS Harmonized Test Guideline 870.3550 study with
dimethylaminopropylamine. Developmental toxicity was not observed,
whereas parental toxicity was manifested as decreased body-weight gain
and clinical signs. Susceptibility was not demonstrated in the
offspring in a rat developmental toxicity study with isopropylamine
following inhalation exposure. Developmental toxicity was not observed,
whereas parental toxicity was manifested as decreased body weight and
body-weight gain. In developmental toxicity studies with ethanolamine
following dermal (rat and rabbit) exposure, developmental and maternal
toxicity were not observed. In a developmental toxicity study,
increased susceptibility to the offspring was not observed following
oral exposure to ethanolamine. Developmental toxicity was observed
(decreased body weight in female fetuses on PND 1-4) at the same dose
level where maternal toxicity was observed (decreased body weight
during the latter part of gestation and throughout lactation). Since a
clear NOAEL of 120 mg/kg/day was identified for offspring effects, and
the selected point of departure of 50 mg/kg/day (mortality and clinical
signs) for the dietary and inhalation risk assessments is protective of
the offspring effects, there are no residual concerns.
There is no evidence in the available toxicity studies or
scientific literature to indicate neurotoxic effects of these amines in
laboratory animals. The clinical signs observed in females in the 28-
day study with dimethylaminopropylamine (stilted gait and decreased
spontaneous activity are considered agonal in nature.
The prenatal developmental and reproduction studies with
alkylbenzene sulfonates showed no qualitative or quantitative evidence
of increased susceptibility. Several reproduction and many
developmental studies have been performed with alkylbenzene sulfonates
in a number of animal species. In the developmental studies, whenever
toxicity was observed in adults, it was generally for mild effects
(slight body weight changes, intestinal disturbances) except for severe
dermal irritation effects in dermal developmental studies. Any
developmental toxicity observed in these same studies included minor
increases in visceral/skeletal anomalies and some fetal losses; but
only at maternally toxic doses. In one reproduction study, there were
slight changes in hematology and histopathology (both within historical
control ranges) and slight decreases in body weight in the offspring at
the highest dose of 250 mg/kg/day (at which there were no effects on
the parental generation). There were no effects in either the parents
or offspring in the other two alkyl benzensulfonate reproductive
toxicity studies at the high dose tested of 70 and 170 mg/kg/day,
respectively.
ii. Diethanolamine salt of alkyl (C8-C24)
benzenesulfonic acid (DEA). There is no OPPTS Harmonized Test Guideline
870.3650 combined repeated dose toxicity study with the reproduction/
developmental toxicity screening test available on DEA. The toxicology
database on DEA consists of open literature studies that include oral
and dermal exposure developmental toxicity studies in rats and a dermal
exposure developmental toxicity study in rabbits. There are no
reproductive toxicity or neurotoxicity studies available on DEA.
No evidence of increased susceptibility to the offspring of rats or
rabbits following prenatal dermal exposure was located. There was
qualitative prenatal susceptibility in the rat oral developmental
toxicity study. The developmental findings with a NOAEL of 50 mg/kg/day
were well-characterized and included increased developmental
sensitivity in the form of increased postnatal day (PND) 0 through 4
mortality and post implantation loss, and reduced pup body weight at
125 mg/kg/day (developmental LOAEL). The maternal toxicity NOAEL/LOAEL
of 50/125 mg/kg/day was based on increased absolute liver weight.
Developmental toxicity was demonstrated in the rat following dermal
exposure to the maternal animal during gestation days (GD) 6 through
15, as evidenced by increased incidence of skeletal variations at 1500
mg/kg/day (HDT). The NOAEL for developmental toxicity was 500 mg/kg/
day; the LOAEL for maternal toxicity was 150 mg/kg (LDT) based on
microcytic anemia with abnormal red blooc cell morphology. The degree
of concern for the increased qualitative susceptibility seen in the
oral developmental toxicity study in rats (prenatal exposure) is low
since a clear NOAEL/LOAEL was established for oral developmental
toxicity and since a more sensitive endpoint of concern (48 mg/kg/day,
the NOAEL from the rat subchronic toxicity study) has been utilized in
assessing the risks from incidential and chronic oral exposure to the
diethanolamine salt of alkyl (C8-C24) benzenesulfonic acid.
Demyelination has been observed in the brain (medulla) and spinal
cord of rats following oral and dermal exposure, and decreased testis
and epididymis weights associated with degeneration of seminiferous
epithelium, decreased numbers of spermatogenic cells, reduced size of
seminiferous tubules, decreased sperm; decreased sperm motility and
sperm count have been observed in male rats following oral exposure.
DEA is structurally related to the essential nutrient choline, and
choline deficiency during pregnancy has been shown to reduce
neurogenesis and increase apoptosis in rat and mouse fetal hippocampus.
In the open literature, DEA has been shown to alter neurogenesis and
induce apoptosis in fetal mouse hippocampus following dermal exposure
of the maternal animal to DEA during pregnancy.
The existing toxicology database is not adequate for assessing the
sensitivity of infants and children to DEA exposure because a
reproduction study is not available and in light of the findings in
adult animals (demyelination in the brain and spinal cord and
degeneration of the seminiferous tubules of the testis) that suggest
the potential for developmental, reproductive, and/or
neurodevelopmental toxicity in the young animal. The particular
findings in the parental animals lead to uncertainties for the
offspring. There is a concern for neurodevelopment since this is not
addressed in the currently available database.
3. Conclusion.--i. Dimethylaminopropylamine, isopropylamine,
ethanolamine, and triethanolamine salts of alkyl (C8-
C24) benzenesulfonic acid. EPA has determined that reliable
data show that the safety of infants and children would be adequately
protected if the
[[Page 38933]]
FQPA SF were reduced to 1X. That decision is based on the following
findings:
a. The toxicity database for dimethylaminopropylamine,
isopropylamine, ethanolamine, and triethanolamine salts of alkyl
(C8-C24) benzenesulfonic acid is considered
adequate for assessing the risks to infants and children to
dimethylaminopropylamine, isopropylamine, ethanolamine and
triethanolamine salts of alkyl (C8-C24)
benzenesulfonic acid exposures (the available studies are described in
Unit IV.D.2.).
b. No susceptibility was demonstrated in the offspring in the OPPTS
Harmonized Guideline 870.3650 combined repeated dose toxicity study
with the reproduction/developmental toxicity screening test in rats
with isopropylamine dodecylbenzene sulfonate following prenatal and
postnatal exposure.
c. No susceptibility was demonstrated in the offspring in the OPPTS
Harmonized Guideline 870.3550 reproduction/developmental toxicity
screening test with dimethylaminopropylamine following prenatal and
postnatal exposure.
d. No susceptibility was demonstrated in the offspring in an
inhalation developmental toxicity study with isopropylamine.
e. The prenatal developmental and reproduction studies with
alkylbenzene sulfonates showed no qualitative or quantitative evidence
of increased susceptibility. Slight changes in hematology and
histopathology (both within historical control ranges) and slight
decreases in body weight in the offspring at the highest dose of 250
mg/kg/day (at which there were no effects on the parental generation)
were seen with alkylbenzenesulfonate in one reproduction study, however
there were no effects in either the parents or offspring in the other
two alkyl benzensulfonate reproductive toxicity studies at the high
dose tested of 70 mg/kg/day and 170 mg/kg/day, respectively. Since the
selected point of departure of 50 mg/kg/day (mortality and clinical
signs) for the dietary and inhalation risk assessments is protective of
the offspring effects, there are no residual concerns.
f. No susceptibility was demonstrated in the offspring in dermal
(rat and rabbit) and oral (rat) developmental toxicity studies with
ethanolamine. Developmental toxicity was observed following oral
exposure with ethanolamine at the same dose level where maternal
toxicity was observed. Since a clear NOAEL of 120 mg/kg/day was
identified for offspring effects, and the selected point of departure
of 50 mg/kg/day (mortality and clinical signs) for the dietary and
inhalation risk assessments is protective of the offspring effects,
there are no residual concerns.
g. No evidence of neurotoxicity was demonstrated in the database
for alkylbenzene sulfonates, dimethylaminopropylamine, isopropylamine,
ethanolamine, and triethanolamine and isopropylamine salt of
dodecylbenzenesulfonic acid and thus there is no need for a
developmental neurotoxicity study or additional UFs to account for
neurotoxicity.
h. There are no residual uncertainties identified in the exposure
databases. The food and drinking water assessment is not likely to
underestimate exposure to any subpopulation, including those comprised
of infants and children. The food exposure assessments are considered
to be highly conservative as they are based on the use of the highest
tolerance level from the surrogate pesticides for every food and 100
PCT is assumed for all crops. EPA also made conservative (protective)
assumptions in the ground and surface water modeling used to assess
exposure to ASABSA in drinking water. EPA used similarly conservative
assumptions to assess post application exposure of children as well as
incidental oral exposure of toddlers. These assessments will not
underestimate the exposure and risks posed by ASABSA.
ii. Diethanolamine salts of alkyl (C8-C24)
benzenesulfonic acid. EPA has determined that the FQPA SF should be
retained. That decision is based on the following findings:
a. Although no increased susceptibility was demonstrated in the
offspring in the available dermal studies in rats and rabbits following
prenatal exposure to DEA, and the degree of concern is low for the
increased qualitative susceptibility seen in the oral developmental
toxicity study in rats, considering the limited data in the literature
on DEA, which indicate a potential for developmental and/or
reproductive and/or developmental neurotoxicity effects, the toxicology
database for DEA is not considered adequate for assessing the
sensitivity of infants and children to DEA when used as an inert
ingredient (the available studies are described in Unit IV.D.2.).
b. There are no neurotoxicity studies available on DEA.
c. There are no reproductive toxicity studies available on DEA.
d. There are no developmental toxicity studies available on DEA
that assess neurodevelopment.
E. Aggregate Risks and Determination of Safety
EPA determines whether acute and chronic pesticide exposures are
safe by comparing aggregate exposure estimates to the aPAD and cPAD.
The aPAD and cPAD represent the highest safe exposures, taking into
account all appropriate SFs. EPA calculates the aPAD and cPAD by
dividing the POD by all applicable UFs. For linear cancer risks, EPA
calculates the probability of additional cancer cases given the
estimated aggregate exposure. Short-, intermediate-, and chronic-term
risks are evaluated by comparing the estimated aggregate food, water,
and residential exposure to the POD to ensure that the MOE called for
by the product of all applicable UFs is not exceeded.
1. Acute risk.There was no hazard attributable to a single exposure
seen in the toxicity database for ASABSA. Therefore, ASABSA are not
expected to pose an acute risk.
2. Chronic risk. A chronic aggregate risk assessment takes into
account exposure estimates from chronic dietary consumption of food and
drinking water. Using the exposure assumptions discussed in this unit
for chronic exposure, including the limitation of use of diethanolamine
salts of alkyl (C8-C24) benzenesulfonic acid to
not more than 7% of the pesticide product, the chronic dietary exposure
from food and water to dimethylaminopropylamine, isopropylamine,
ethanolamine and triethanolamine salts of alkyl (C8-
C24) benzenesulfonic acid, is 23% of the cPAD for the U.S.
population and 75% of the cPAD for children 1 to 2 years old, the most
highly exposed population subgroup. The chronic dietary exposure from
food and water to diethanolamine salts of alkyl (C8-
C24) benzenesulfonic acid is 19% of the cPAD for the U.S.
population and 56% of the cPAD for children 1 to 2 years old, the most
highly exposed population subgroup.
3. Short-term risk. Short-term aggregate exposure takes into
account short-term residential exposure plus chronic exposure to food
and water (considered to be a background exposure level).
ASABSA are used as inert ingredients in pesticide products that are
currently registered for uses that could result in short-term
residential exposure and the Agency has determined that it is
appropriate to aggregate chronic exposure through food and water with
short-term residential exposures to ASABSA. Using the exposure
assumptions described in this unit, EPA has concluded that the combined
short-
[[Page 38934]]
term aggregated food, water, and residential exposures result in
aggregate MOEs of 220 and 260 for adult males and females,
respectively. Adult residential exposure combines high end outdoor
dermal and inhalation handler exposure with a high end post application
dermal exposure from contact with treated lawns. EPA has concluded the
combined short-term aggregated food, water, and residential exposures
result in an aggregate MOE of 110 for children. Children's residential
exposure includes total exposures associated with contact with treated
lawns (dermal and hand-to-mouth exposures). As the level of concern is
for MOEs that are lower than 100, these MOEs are not of concern.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account intermediate-term residential exposure plus chronic
exposure to food and water (considered to be a background exposure
level).
ASABSA are used as inert ingredients in pesticide products that are
currently registered for uses that could result in intermediate-term
residential exposure and the Agency has determined that it is
appropriate to aggregate chronic exposure through food and water with
intermediate-term residential exposures to ASABSA. Using the exposure
assumptions described in this unit, EPA has concluded that the combined
intermediate-term aggregated food, water, and residential exposures
result in aggregate MOEs of 540 and 570 for adult males and females,
respectively. Adult residential exposure includes high end post
application dermal exposure from contact with treated lawns. EPA has
concluded that the combined intermediate-term aggregated food, water,
and residential exposures result in an aggregate MOE of 110 for
children. Children's residential exposure includes total exposures
associated with contact with treated lawns (dermal and hand-to-mouth
exposures). As the level of concern is for MOEs that are lower than
100, these MOEs are not of concern.
5. Aggregate cancer risk for U.S. population. The Agency has not
identified any concerns for carcinogenicity relating to ASABSA.
6. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population or to infants and children from aggregate
exposure to residues of ASABSA.
V. Other Considerations
A. Analytical Enforcement Methodology
An analytical method is not required for enforcement purposes since
the Agency is establishing an exemption from the requirement of a
tolerance without any numerical limitation.
B. International Residue Limits
The Agency is not aware of any country requiring a tolerance for
ASABSA nor have any CODEX Maximum Residue Levels been established for
any food crops at this time.
VI. Conclusion
Therefore, an exemption from the requirement of a tolerance is
established for residues of dimethylaminopropylamine, isopropylamine,
ethanolamine, and triethanolamine salts of alkyl (C8-
C24) benzenesulfonic acid when used as an inert ingredient
in pesticide formulations applied to growing crops under 40 CFR 180.920
and to animals under 40 CFR 180.930 and to diethanolamine salts of
alkyl (C8-C24) benzenesulfonic acid when used as
an inert ingredient at levels not to exceed 7% by weight in pesticide
formulations applied to growing crops under 40 CFR 180.920 and to
animals under 40 CFR 180.930.
VII. Statutory and Executive Order Reviews
This final rule establishes an exemption from the requirement of
tolerances under section 408(d) of FFDCA in response to a petition
submitted to the Agency. The Office of Management and Budget (OMB) has
exempted these types of actions from review under Executive Order
12866, entitled Regulatory Planning and Review (58 FR 51735, October 4,
1993). Because this final rule has been exempted from review under
Executive Order 12866, this final rule is not subject to Executive
Order 13211, entitled Actions Concerning Regulations That Significantly
Affect Energy Supply, Distribution, or Use (66 FR 28355, May 22, 2001)
or Executive Order 13045, entitled Protection of Children from
Environmental Health Risks and Safety Risks (62 FR 19885, April 23,
1997). This final rule does not contain any information collections
subject to OMB approval under the Paperwork Reduction Act (PRA), 44
U.S.C. 3501 et seq., nor does it require any special considerations
under Executive Order 12898, entitled Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994).
Since tolerances and exemptions that are established on the basis
of a petition under section 408(d) of FFDCA, such as the exemptions in
this final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled Federalism (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
Consultation and Coordination with Indian Tribal Governments (65 FR
67249, November 9, 2000) do not apply to this final rule. In addition,
this final rule does not impose any enforceable duty or contain any
unfunded mandate as described under Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (Public Law 104-4).
This action does not involve any technical standards that would
require Agency consideration of voluntary consensus standards pursuant
to section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272
note).
VIII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. EPA will submit a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives, and the Comptroller General of the
United States prior to publication of this final rule in the Federal
Register. This final rule is not a ``major rule'' as defined by 5
U.S.C. 804(2).
[[Page 38935]]
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: July 30, 2009.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
0
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
0
1. The authority citation for part 180 continues to read asfollows:
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. In Sec. 180.920, the table is amended by adding alphabetically the
following inert ingredients:
Sec. 180.920 Inert ingredients used pre-harvest; exemptions from the
requirement of a tolerance.
* * * * *
------------------------------------------------------------------------
Inert Ingredients Limits Uses
------------------------------------------------------------------------
* * * * * * *
Diethanolamine salts of alkyl Not to exceed 7% Surfactants,
(C8-C24) benzenesulfonic acid of pesticide related adjuvants
(CAS Reg. Nos. 26545-53-9 and formulation. of surfactants
68953-97-9).
* * * * * * *
Dimethylaminopropylamine, Surfactants,
isopropylamine, ethanolamine, related adjuvants
and triethanolamine salts of of surfactants
alkyl (C8-C24) benzenesulfonic
acid (CAS Reg. Nos. 26264-05-1,
27323-41-7, 55470-69-4, 68411-
31-4, 68584-24-7, 68584-25-8,
68648-81-7, 68648-96-4, 68649-
00-3, 68910-32-7, 68953-93-5,
90194-42-6, 90194-53-9, 90218-
35-2, 157966-96-6, 319926-68-6,
877677-48-0, 1093628-27-3).
* * * * * * *
------------------------------------------------------------------------
0
3. In Sec. 180.930, the table is amended by adding alphabetically the
following inert ingredients:
Sec. 180.930 Inert ingredients applied to animals; exemptions from
the requirement of a tolerance.
* * * * *
------------------------------------------------------------------------
Inert Ingredients Limits Uses
------------------------------------------------------------------------
* * * * * * *
Diethanolamine salts of alkyl Not to exceed 7% Surfactants,
(C8-C24) benzenesulfonic acid of pesticide related adjuvants
(CAS Reg. Nos. 26545-53-9 and formulation. of surfactants
68953-97-9).
* * * * * * *
Dimethylaminopropylamine, Surfactants,
isopropylamine, ethanolamine, related adjuvants
and triethanolamine salts of of surfactants
alkyl (C8-C24) benzenesulfonic
acid (CAS Reg. Nos. 26264-05-1,
27323-41-7, 55470-69-4, 68411-
31-4, 68584-24-7, 68584-25-8,
68648-81-7, 68648-96-4, 68649-
00-3, 68910-32-7, 68953-93-5,
90194-42-6, 90194-53-9, 90218-
35-2, 157966-96-6, 319926-68-6,
877677-48-0, 1093628-27-3).
* * * * * * *
------------------------------------------------------------------------
[FR Doc. E9-18698 Filed 8-4-09; 8:45 am]
BILLING CODE 6560-50-S