[Federal Register Volume 75, Number 159 (Wednesday, August 18, 2010)]
[Rules and Regulations]
[Pages 50896-50902]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-20318]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2008-0474; FRL-8838-9]
Diethylene Glycol (DEG); Exemption from the Requirement of a
Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes an exemption from the requirement
of a tolerance for residues of diethylene glycol (DEG) (CAS No. 111-46-
6) when used as an inert ingredient as a solvent, stabilizer and/or
antifreeze within pesticide formulations without limitation, under 40
CFR 180.920, for use on growing crops and raw agricultural commodities
pre-harvest Huntsman, Dow AgroSciences L.L.C., Nufarm Americas Inc.,
BASF, Stepan Company, Loveland Products Inc., and Rhodia Inc. submitted
a petition to EPA under the Federal Food, Drug, and Cosmetic Act
(FFDCA), requesting establishment of an exemption from the requirement
of a tolerance. This regulation eliminates the need to establish a
maximum permissible level for residues of DEG.
DATES: This regulation is effective August 18, 2010. Objections and
requests for hearings must be received on or before October 18, 2010,
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-2008-0474. 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: Lisa Austin, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-7894; 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 producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
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 provides
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
[[Page 50897]]
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 Get Electronic Access to Other Related Information?
You may access a frequently updated electronic version of 40 CFR
part 180 through the Government Printing Office's e-CFR cite at http://www.gpoaccess.gov/ecfr. To access the OPPTS harmonized test guidelines
referenced in this document electronically, please go to http://www.epa.gov/oppts and select ``Test Methods and Guidelines.''
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. The EPA procedural regulations which
govern the submission of objections and requests for hearings appear in
40 CFR part 178. 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-2008-0474 in the subject line on the first page of
your submission. All objections and requests for a hearing must be in
writing, and must be received by the Hearing Clerk on or before October
18, 2010. Addresses for mail and hand delivery of objections and
hearing requests are provided in 40 CFR 178.25(b).
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 your copies, identified by docket ID
number EPA-HQ-OPP-2008-0474, 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. Petition for Exemption
In the Federal Register of July 9, 2008 (73 FR 39289) (FRL-8371-2),
EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C. 346a,
announcing the filing of a pesticide petition (PP 8E7355) by Huntsman,
Dow AgroSciences L.L.C., Nufarm Americas Inc., BASF, Stepan Company,
Loveland Products Inc., and Rhodia Inc. The petition requested that 40
CFR 180.920 be amended by establishing an exemption from the
requirement of a tolerance for residues of DEG (CAS No. 111-46-6) when
used as an inert ingredient for use as a solvent, stabilizer and/or
antifreeze without limitation in pesticide formulations applied to use
on growing crops and raw agricultural commodities pre-harvest. That
notice referenced a summary of the petition prepared by Huntsman, Dow
AgroSciences L.L.C., Nufarm Americas Inc., BASF, Stepan Company,
Loveland Products Inc., and Rhodia Inc., the petitioners, which is
available in the docket, http://www.regulations.gov. The Agency
received one comment in response to the notice of filing. The comment
was received from a private citizen who opposed the authorization to
sell any pesticide that leaves a residue on food. The Agency
understands the commenter's concerns and recognizes that some
individuals believe that no residue of pesticides should be allowed.
However, under the existing legal framework provided by section 408 of
FFDCA, EPA is authorized to establish pesticide tolerances or
exemptions where persons seeking such tolerances or exemptions have
demonstrated that the pesticide meets the safety standard imposed by
the statute.
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; 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(c)(2)(A)(i) of FFDCA allows EPA to establish an
exemption from the requirement for 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 establishes exemptions from the requirement of a tolerance only
in those cases where it can be clearly demonstrated that the risks from
aggregate exposure to pesticide chemical residues under reasonably
foreseeable circumstances will pose no appreciable risks to human
health. In order to determine the risks from aggregate exposure to
pesticide inert ingredients, the Agency considers the toxicity of the
inert in conjunction with possible exposure to residues of the inert
ingredient through food, drinking water, and through other exposures
that occur as a result of pesticide use in residential settings. If EPA
is able to determine that a finite tolerance is not necessary to ensure
that there is a reasonable certainty that no harm will result from
aggregate exposure to the inert ingredient, an exemption from the
requirement of a tolerance may be established.
Consistent with section 408(c)(2)(A) of FFDCA, and the factors
specified in FFDCA section 408(c)(2)(B), EPA has
[[Page 50898]]
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 DEG
including exposure resulting from the exemption established by this
action. EPA's assessment of exposures and risks associated with DEG
follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered their
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. Specific information on the studies received and the nature
of the adverse effects caused by DEG as well as the no-observed-
adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-
level (LOAEL) from the toxicity studies are discussed in this unit.
DEG has low acute toxicity via the oral route in animals. It has
low acute toxicity via the dermal route. Data were not available
regarding dermal irritation and sensitization. Data on humans show that
the probable LD50 of DEG is approximately 0.5-5 gram/
kilogram (g/kg) and that it is not irritating to the eyes or skin.
However, a man developed allergic dermatitis 2-4 weeks after smoking
cigarettes containing DEG. He also had a local reaction in a 24 hours
covered patch test with DEG.
In subchronic oral studies in animals, the kidney, liver and
hematopoietic systems were most often the target organs. In subchronic
studies, males were more susceptible to kidney toxicity. Kidney lesions
occurred in the range of 100 to 180 milligrams/kilograms/day (mg/kg/
day) and were manifested as tubular damage. DEG caused increased size
and hydropic changes in the liver and oxalate crystals were found in
the urinary bladder and kidney at >100 mg/kg/day. The NOAEL for DEG in
the subchronic rat study was 50 mg/kg/day, based on increased urinary
oxalate at 100 mg/kg/day. Some subchronic studies available in the
literature show kidney toxicity at very high doses. In addition, kidney
toxicity was only evident at very high doses in chronic studies.
Several developmental studies in rodents were available for review.
In these studies, maternal and developmental toxicity occurred at doses
(> 1,118 mg/kg/day) that were above the limit dose of 1,000 mg/kg/day.
Two reproduction toxicity studies in rodents were available for review.
Again, maternal and offspring toxicity was observed at high doses (>
1,500 mg/kg/day).
Several mutagenicity studies (Ames test and chromosome aberration)
with DEG were available for review. The TA104 strain was slightly
positive in one assay with metabolic activity. All in vivo assays were
negative. Therefore, based on the overall weight of evidence, DEG is
not considered mutagenic.
In chronic oral studies, the kidney, liver and hematopoietic
systems were most often the target organs. In chronic studies, kidney
neuropathy occurred at dosages of greater than 920 mg/kg/day and was
manifested as epithelial necrosis of the renal tubules. Bladder tumors
were observed at > 1,500 mg/kg/day; however, these tumors were
associated with irritation from bladder stones. The physiochemical
properties of DEG cause crystal formation and deposition in the kidneys
which leads to irritation, stone formation, kidney damage and tumor
formation. Therefore, protecting from crystal formation would be
protective of subsequent kidney damage and tumor formation. Also, a
Soviet study reported no evidence of cancer in a group of 90 workers
exposed to DEG for 1 to 9 years. In addition, DEG is not listed as a
carcinogen byAmerican Conference of Industrial Hygienist,(ACGIH),
International Agency for Research on Cancer (IARC), National Toxicology
Program,(NTP) or California Proposition 65.
Metabolism studies demonstrated that DEG was rapidly absorbed and
primarily excreted via the urine.
B. Toxicological Points of Departure/Levels of Concern
Once a pesticide's toxicological profile is determined, EPA
identifies toxicological points of departure (POD) and levels of
concern to use in evaluating the risk posed by human exposure to the
pesticide. For hazards that have a threshold below which there is no
appreciable risk, the toxicological POD is used as the basis for
derivation of reference values for risk assessment. PODs are developed
based on a careful analysis of the doses in each toxicological study to
determine the dose at which no adverse effects are observed (the NOAEL)
and the lowest dose at which adverse effects of concern are identified
(the LOAEL). Uncertainty/safety factors are used in conjunction with
the POD to calculate a safe exposure level - generally referred to as a
population-adjusted dose (PAD) or a reference dose (RfD) - and a safe
margin of exposure (MOE). 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 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.
The available toxicity studies suggest that the DEG manifested
toxicity appears to occur following high repeated doses. In
developmental toxicity study in rats, mice and rabbits, the clear
NOAELs were observed at doses 559 mg/kg/day and above. In reproduction
studies in mice and rats, the lowest NOAEL was 300 mg/kg/day (highest
dose tested) and one study in mice had a NOAEL of 610 mg/kg/day with a
LOAEL of 3,060 mg/kg/day. The NOAEL for carcinogenicity studies in rats
was 1,000 mg/kg/day and above. One chronic toxicity study in rats had a
LOAEL of 1,000 mg/kg/day. The subchronic studies gave confounding
results in terms of NOAEL for the study. In a subchronic study in rats
(feeding), the reported NOAEL was 400 mg/kg/day and the second study in
rats reported the NOAEL of 50 mg/kg/day. However, in other studies
reported in the literature, no overt toxicity was observed in 20 mice/
sex maintained on a diet containing 5.2 g/kg bw/day for 15 to 18 weeks.
Kidney and liver damage occurred in rabbits given DEG by gavage or in
drinking water at about 15 gram/kilograms bodyweight/day (g/kg bw/day)
for up to 28 days, and also in guinea-pigs, cats and dogs subjected to
similar exposures. Based on the overall weight of evidence from all
studies, a NOAEL of 100 mg/kg/day is considered protective for DEG-
mediated toxicity for estimating risk via all routes of exposure. In
the absence of inhalation studies, 100% inhalation is assumed. The
dermal absorption factor of 25% was estimated based on dermal
absorption of structurally similar compound for converting oral to
dermal equivalent dose.
Bladder tumors were observed following treatment with DEG at doses
> 1,500 mg/kg/day. However, these tumors appear to be secondary to
irritation and regenerative proliferation associated with the formation
of urinary tract crystals/calculi. This is commonly seen for bladder
carcinogenesis in rodents for non-genotoxic chemicals of the
sulfonamide class. Since DEG presents no concern for mutagenicity and
based on knowledge about other chemicals, EPA considers DEG as not
[[Page 50899]]
likely to be a human carcinogen. The cRfD (1.0 mg/kg/day) was
established based on these precursor effects observed at >300 mg/kg/
day. Therefore, the cRfD is considered adequately protective of any
cancer or pre-cancerous effects seen in the carcinogenicity studies.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to DEG, EPA considered exposure under the proposed exemption
from the requirement of a tolerance. EPA assessed dietary exposures
from DEG in food as follows:
i. Acute exposure. No adverse effects attributable to a single
exposure of DEG were seen in the toxicity databases. Therefore, an
acute dietary risk assessment for DEG is not necessary.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment, 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 DEG. 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 is contained in the memorandum entitled ``Alkyl Amines
Polyalkoxylates (Cluster 4): Acute and Chronic Aggregate (Food and
Drinking Water) Dietary Exposure and Risk Assessments for the Inerts,''
(D361707, S. Piper, 2/25/09) and can be found at http://www.regulations.gov 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 levels 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 in relation to that of
the active ingredient.
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. In summary,
EPA chose a very conservative method for estimating what level of inert
residue could be on food, 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. As discussed in this unit, the Agency has not
identified any concerns for carcinogenicity relating to DEG, and,
therefore, a dietary exposure assessment to assess cancer risk is
unnecessary.
2. Dietary exposure from drinking water. For the purpose of the
screening level dietary risk assessment to support this request for an
exemption from the requirement of a tolerance for DEG, a conservative
drinking water concentration value of 100 parts per billion based on
screening level modeling was used to assess the contribution to
drinking water for the chronic dietary risk assessments for parent
compound. 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., textiles (clothing and diapers), carpets, swimming
pools, and hard surface disinfection on walls, floors, tables).
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). DEG may be used in inert ingredients in products
that are registered for specific uses that may result in residential
exposure. A screening level residential exposure and risk assessment
was completed for products containing DEG as inert ingredients. The DEG
inerts may be present in consumer personal (care) products and
cosmetics. The Agency selected representative scenarios, based on end-
use product application methods and labeled application rates. The
Agency conducted an assessment to represent worst-case residential
exposure by assessing DEG in pesticide formulations (Outdoor Scenarios)
and DEG in disinfectant-type uses (Indoor Scenarios). The Agency is not
aware of any use of DEG in hard surface cleaning products. However,
this scenario was used for this assessment considering wide use of DEG
in other products. Therefore, the Agency assessed the disinfectant-type
products containing DEG using exposure scenarios used by the
Antimicrobials Division in EPA's Office of Pesticide Programs to
represent worst-case residential handler exposure. Further details of
this residential exposure and risk analysis can be found at http://www.regulations.gov in the memorandum entitled: ``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
[[Page 50900]]
Formulations,'' (D364751, 5/7/09, Lloyd/LaMay 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 DEG to share a common mechanism of toxicity with
any other substances, and DEG does not appear to produce a toxic
metabolite produced by other substances. For the purposes of this
tolerance action, therefore, EPA has assumed that DEG does 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 Food Quality
Protection Act (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. There was no evidence of
increased susceptibility of infants and children following prenatal
exposure to DEG in mice, and rabbits. In mice and rabbits, the maternal
or developmental toxicity were seen at or above the limit dose except
in one study in mice where the maternal toxicity NOAEL was 559 mg/kg/
day and developmental toxicity NOAEL was 2,759 mg/kg/day. In these
studies with mice and rabbits, developmental effects were observed in
the presence of maternal toxicity or at a dose above the dose that
produced maternal toxicity. There was some evidence of increased
susceptibility in the rat developmental toxicity study. In the rat
developmental toxicity study, the maternal NOAEL was 4,472 mg/kg/day
and the developmental NOAEL was 1,178 mg/kg/day. However, the concern
for this increased susceptibility was low since the skeletal variations
were seen at dose level above the limit dose.
Several reproduction studies are available in the database. The
effects seen in these studies are characterized as high dose effects.
There was no evidence of increased susceptibility of infants and
children following prenatal and postnatal exposure to DEG in mice and
rats except in one study in mice. In one reproduction study in mice
(drinking water), the NOAEL for developmental toxicity was 610 mg/kg/
day and the LOAEL was 3,060 mg/kg/day. The maternal toxicity NOAEL in
the mice reproduction was 2,060 mg/kg/day. The reproduction study in
mice suggest some evidence of increased susceptibility, however, the
concern is low because the developmental effects were seen at 3 times
higher dose than the limit dose of 1,000 mg/kg/day. Overall, based on
available data in mice, rats and rabbits, the concern for isolated
susceptibility is low because the increased susceptibility was seen at
or above the limit dose and they were not reproduced in other studies
conducted in same species.
3. Conclusion. EPA has determined that reliable data show the
safety of infants and children would be adequately protected if the
FQPA SF were reduced to 1X. That decision is based on the following
findings:
i. The toxicity database for DEG is adequate. The following
acceptable studies are available: Developmental toxicity studies in
mice, rats and rabbits, reproduction study in mice and rats and
subchronic and chronic studies including carcinogenicity studies and
mutagenicity studies.
ii. Clinical signs of neurotoxicity were reported in acute studies
conducted at very high doses. However, no significant clinical signs
were observed in repeated dose studies and no increased susceptibility
was seen in the available developmental or reproduction studies at
doses below the limit dose of 1,000 mg/kg/day. Based on overall weight
of evidence, EPA concluded that the developmental neurotoxicity is not
required.
iii. There was no evidence of increased susceptibility of infants
and children following prenatal exposure to DEG in mice, and rabbits.
The developmental study in the rat and reproduction study in mice
suggest some evidence of increased susceptibility of infants and
children, however, the concern is low because the developmental effects
were seen at higher doses than the limit dose of 1,000 mg/kg/day and
there is a clear NOAEL established in these studies. Overall, based on
available data in mice, rats and rabbits, the concern for isolated
susceptibility is low because the increased susceptibility was seen at
or above the limit dose and they were not reproduced in other studies
conducted in same species.
iv. Signs of potential immunotoxicity were not observed in any of
the submitted studies.
v. There are no residual uncertainties identified in the exposure
databases. The dietary food exposure assessments were performed based
on the assumptions of 100% crop treated and tolerance-level residues.
EPA made conservative (protective) assumptions in the ground and
surface water modeling used to assess exposure to DEG in drinking
water. EPA used similarly conservative assumptions to assess
postapplication exposure of children as well as incidental oral
exposure of toddlers. These assessments will not underestimate the
exposure and risks posed by DEG.
E. Aggregate Risks and Determination of Safety
EPA determines whether acute and chronic dietary pesticide
exposures are safe by comparing aggregate exposure estimates to the
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA
calculates the lifetime probability of acquiring cancer 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 appropriate PODs to ensure that an
adequate MOE exists.
1. Acute risk. An acute aggregate risk assessment takes into
account acute exposure estimates from dietary consumption of food and
drinking water. No adverse effect resulting from a single oral exposure
was identified and no acute dietary endpoint was selected. Therefore,
DEG is not expected to pose an acute risk.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
DEG from food and water will utilize 0.62% of the cPAD for children 1
to 2 years old, the population group receiving the greatest exposure.
3. Short-term risk. Short-term aggregate exposure takes into
account short-term residential exposure plus chronic exposure to food
and water
[[Page 50901]]
(considered to be a background exposure level).
DEG is currently used as an inert ingredient in pesticide products
that are 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 DEG.
Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined short-term food, water,
and residential exposures result in aggregate MOEs of 132 for both
adult males and females. Adult residential exposure combines high end
dermal and inhalation handler exposure from indoor hand wiping 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 114 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).
DEG is currently used as an inert ingredient in pesticide products
that are 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 DEG.
Using the exposure assumptions described in this unit for
intermediate-term exposures, EPA has concluded that the combined
intermediate-term food, water, and residential exposures result in
aggregate MOEs of 388 for adult males and females. Adult residential
exposure includes high end post application dermal exposure from
contact with treated lawns. EPA has concluded the combined
intermediate-term aggregated food, water, and residential exposures
result in an aggregate MOE of 133 for children. Children's residential
exposure includes total exposures associated with contact with treated
lawns (dermal and hand-to-mouth exposures). Because EPA's level of
concern for DEG is a MOE of 100 or below, these MOEs are not of
concern.
5. Aggregate cancer risk for U.S. population. DEG is not expected
to be carcinogenic since there were no triggers for carcinogenicity in
the published study and a lack of systemic toxicity in the 1-generation
reproduction study in rats as well as a negative response for
mutagenicity.
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 DEG residues.
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
DEG nor have any CODEX Maximum Residue Levels been established for any
food crops at this time.
VI. Conclusions
Therefore, an exemption from the requirement of a tolerance is
established under 40 CFR 180.920 for DEG (Cas No. 111-46-6) when used
as an inert ingredient (as a solvent, stabilizer and/or antifreeze
within pesticide formulations/products without limitation) in pesticide
formulations applied to growing crops and raw agricultural commodities
pre-harvest.
VII. Statutory and Executive Order Reviews
This final rule establishes an exemption from the requirement of a
tolerance 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 exemption 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
[[Page 50902]]
a ``major rule'' as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: August 6, 2010.
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 as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. In Sec. 180.920, in the table, add alphabetically the following
inert ingredient to read as follows:
Sec. 180.910 Inert ingredients used pre-harvest; exemptions from the
requirement of a tolerance.
* * * * *
------------------------------------------------------------------------
Inert ingredients Limits Uses
------------------------------------------------------------------------
* * * * * * *
Diethylene Glycol (CAS No. 111- Without limitation Solvent,
46-6) stabilizer and/or
antifreeze
* * * * * * *
------------------------------------------------------------------------
[FR Doc. 2010-20318 Filed 8-17-10; 8:45 am]
BILLING CODE 6560-50-S