[Federal Register Volume 80, Number 196 (Friday, October 9, 2015)]
[Rules and Regulations]
[Pages 61125-61129]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-25589]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2014-0630; FRL-9934-17]


Dimethyl Sulfoxide; Exemption From the Requirement of a Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation amends the exemption from the requirement of a 
tolerance for residues of dimethyl sulfoxide (CAS Reg. No. 67-68-5) 
when used as an inert ingredient (solvent, co-solvent) in pesticide 
formulations applied to growing crops (pre-emergent use only) to 
include use after the crop emerges from the soil but before harvest 
provided that the potential for increased residues of the formulation's 
active ingredient(s) in or on food commodities has been assessed. ISK 
BioSciences submitted a petition to EPA under the Federal Food, Drug, 
and Cosmetic Act (FFDCA), requesting an amendment to an existing 
exemption from the requirement of a tolerance. This regulation 
eliminates the need to establish a maximum permissible level for 
residues of dimethyl sulfoxide.

DATES: This regulation is effective October 9, 2015. Objections and 
requests for hearings must be received on or before December 8, 2015, 
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: The docket for this action, identified by docket 
identification (ID) number EPA-HQ-OPP-2014-0630, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory 
Public Docket (OPP Docket) in the Environmental Protection Agency 
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334, 
1301 Constitution Ave. NW., Washington, DC 20460-0001. The Public 
Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through 
Friday, excluding legal holidays. The telephone number for the Public 
Reading Room is (202) 566-1744, and the telephone number for the OPP 
Docket is (703) 305-5805. Please review the visitor instructions and 
additional information about the docket available at http://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Susan Lewis, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; main telephone 
number: (703) 305-7090; email 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. 
The following list of North American Industrial Classification System 
(NAICS) codes is not intended to be exhaustive, but rather provides a 
guide to help readers determine whether this document applies to them. 
Potentially affected entities may include:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).

[[Page 61126]]

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 site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

C. How can I file an objection or hearing request?

    Under FFDCA section 408(g), 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-2014-0630 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 
December 8, 2015. 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 (excluding any Confidential Business Information (CBI)) for 
inclusion in the public docket. Information not marked confidential 
pursuant to 40 CFR part 2 may be disclosed publicly by EPA without 
prior notice. Submit the non-CBI copy of your objection or hearing 
request, identified by docket ID number EPA-HQ-OPP-2014-0630, by one of 
the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be CBI or other 
information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 
20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at http://www.epa.gov/dockets/contacts.html.

Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at http://www.epa.gov/dockets.

II. Petition for Exemption

    In the Federal Register of March 4, 2015 (80 FR 11611) (FRL-9922-
68), EPA issued a document pursuant to FFDCA section 408, 21 U.S.C. 
346a, announcing the filing of a pesticide petition (IN-10713) by ISK 
BioSciences, 7470 Auburn Rd., Suite A, Concorde, OH 44077. The petition 
requested that 40 CFR 180.920 be amended by modifying an exemption from 
the requirement of a tolerance for residues of dimethyl sulfoxide (CAS 
Reg. No. 67-68-5) when used as an inert ingredient (diluent) at levels 
not to exceed 62% in pesticide formulations containing cyclaniliprole. 
That document referenced a summary of the petition prepared by ISK 
BioSciences, the petitioner, which is available 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 request for a tolerance exemption due to the concern 
regarding the chemical properties of dimethyl sulfoxide that may result 
in increased active ingredient residues. Therefore, the tolerance 
exemption under 40 CFR 180.920 was modified. This limitation is based 
on the Agency's risk assessment which can be found at http://www.regulations.gov in document Dimethyl sulfoxide; Human Health Risk 
Assessment and Ecological Effects 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-
2014-0630.

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 FFDCA section 408(c)(2)(A), and the factors 
specified in FFDCA section 408(c)(2)(B), 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 dimethyl sulfoxide including 
exposure resulting from the exemption established by this action. EPA's 
assessment of exposures and risks associated with dimethyl sulfoxide 
follows.

[[Page 61127]]

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 dimethyl sulfoxide 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.
    Dimethyl sulfoxide has low acute toxicity via the oral and dermal 
in rats and mice and inhalation route in rats. The acute oral lethal 
dose (LD)50 = 7,920 milligrams/kilograms (mg/kg) in rats and 
mice. The acute dermal LD50 = 40,000 mg/kg in rats and mice. 
The acute inhalation lethal concentration (LC)50 = 1,600 
milligram/meter\3\ (mg/m\3\) (~277 mg/kg) in rats. It is a dermal, eye 
and gastric irritant in rats and rabbits. It is a sensitizer in guinea 
pigs.
    Overall systemic toxicity with regard to oral and dermal exposure 
to dimethyl sulfoxide is low. The target organ of toxicity is the eye. 
Changes in the eyes, such as refractile changes in the lens and lens 
composition are seen in various animals at doses above the limit dose 
(1,000 mg/kg/day).
    Systemic toxicity is not observed following exposure to dimethyl 
sulfoxide at dose levels up to 1,000 mg/kg/day (the limit dose) in 
subchronic, chronic or reproduction/developmental toxicity studies via 
oral, dermal or inhalation exposures in rats, dogs and rabbits. 
Dimethyl sulfoxide is not expected to be carcinogenic based on the lack 
of mutagenicity and the lack of tumor formation in cancer initiation/
promotion studies. It is not neurotoxic nor immunotoxic.
    Toxicity of dimethyl sulfoxide via the inhalation route of exposure 
is limited to portal of entry effects at 2.783 mg/1 (equivalent to 722 
mg/kg/day).
    In the rat and monkey, dimethyl sulfoxide administered via the oral 
and/or dermal route is rapidly absorbed, metabolized and excreted. 
Excretion is primarily via urine, feces was a minor route in the rat 
only. The major metabolite was dimethyl sulfone. Dimethyl sulfide, 
another metabolite, is eliminated through the breath. There is no 
bioaccumulation.
    Specific information on the studies received and the nature of the 
adverse effects caused by Dimethyl sulfoxide as well as the NOAEL and 
the LOAEL from the toxicity studies can be found at http://www.regulations.gov in the document ``Dimethyl sulfoxide; Human Health 
Risk Assessment and Ecological Effects 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-
2014-0630.

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 indicate that dimethyl sulfoxide has 
low toxicity. These data demonstrated adverse effects only at doses 
[gteqt]1100 mg/kg/day (above the limit dose). Therefore, since no 
endpoint of concern was identified for dimethyl sulfoxide, a 
qualitative risk assessment is appropriate.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to dimethyl sulfoxide, EPA considered exposure under the 
proposed exemption from the requirement of a tolerance. EPA assessed 
dietary exposures from dimethyl sulfoxide in food as follows:
    Dietary exposure can occur from eating foods containing residues of 
dimethyl sulfoxide. Because no hazard endpoint of concern was 
identified for the acute and chronic dietary assessment (food and feed 
uses, a quantitative dietary exposure risk assessment was not 
conducted.
    2. Dietary exposure from drinking water. Since a hazard endpoint of 
concern was not identified for the acute and chronic dietary 
assessment, a quantitative dietary exposure risk assessment for 
drinking water was not conducted.
    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).
    Dimethyl sulfoxide may be used in consumer products that may be 
used around the home. However, based on the lack of toxicity, a 
quantitative exposure assessment from ``residential exposures'' was not 
performed.
    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 dimethyl sulfoxide to share a common mechanism of 
toxicity with any other substances, and dimethyl sulfoxide does not 
appear to produce a toxic metabolite produced by other substances. For 
the purposes of this tolerance action, therefore, EPA has assumed that 
dimethyl sulfoxide 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 Web site 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

[[Page 61128]]

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.
    At this time, there is no concern for potential sensitivity to 
infants and children resulting from exposures to dimethyl sulfoxide. 
There is no reported quantitative or qualitative evidence of increased 
susceptibility of rat or rabbit fetuses to in utero exposure to 
dimethyl sulfoxide in developmental toxicity studies in rats and 
rabbits. No quantitative or qualitative evidence of increased 
susceptibility has been reported following the pre/postnatal exposure 
to rats and rabbits in 2-generation reproduction toxicity studies in 
rats and rabbits. Given the lack of adverse toxicological effects at 
limit dose levels, a safety factor analysis has not been used to assess 
the risk. For these reasons the additional tenfold safety factor is 
unnecessary.

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, 
dimethyl sulfoxide 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 based on the low 
toxicity of dimethyl sulfoxide and since no chronic endpoint was 
identified, chronic risk is not expected.
    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). Because no 
short-term adverse effect was identified, dimethyl sulfoxide is not 
expected to pose a short-term risk.
    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). Because no intermediate-term adverse effect was identified, 
dimethyl sulfoxide is not expected to pose an intermediate-term risk.
    5. Aggregate cancer risk for U.S. population. Based on the lack of 
increased tumor formation in initiation/promotion toxicity studies and 
the lack of mutagenicity, dimethyl sulfoxide is not expected to pose a 
cancer risk to humans.
    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 dimethyl sulfoxide 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.

VI. Conclusions

    Therefore, an exemption from the requirement of a tolerance is 
established under 40 CFR 180.920 for dimethyl sulfoxide (CAS Reg. No. 
67-68-5) when used as an inert ingredient solvent, cosolvent in 
pesticide formulations used before crop emerges from soil or prior to 
formation of edible parts of food plants; for pesticide formulations 
used after crop emerges but before harvest, provided that the potential 
for increased residues of the formulation's active ingredient(s) in or 
on food commodities has been assessed.

VII. Statutory and Executive Order Reviews

    This action establishes a tolerance under FFDCA section 408(d) 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 action has been 
exempted from review under Executive Order 12866, this action 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 action 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 FFDCA section 408(d), such as the tolerance 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 action 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 FFDCA section 408(n)(4). 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 action. In addition, this 
action does not impose any enforceable duty or contain any unfunded 
mandate as described under Title II of the Unfunded Mandates Reform Act 
(UMRA) (2 U.S.C. 1501 et seq.).
    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 (NTTAA) (15 U.S.C. 272 note).

VIII. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.), 
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 
the rule in the Federal

[[Page 61129]]

Register. This action is not 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: September 14, 2015.
 G. Jeffery Herndon,
Acting Director, Registration Division, Office of Pesticide Programs.

    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, add alphabetically the inert ingredient ``Dimethyl 
Sulfoxide (CAS No. 67-68-5)'' to the table to read as follows:


Sec.  180.920  Inert ingredients used pre-harvest; exemptions from the 
requirement of a tolerance.

* * * * *

----------------------------------------------------------------------------------------------------------------
          Inert ingredients                           Limits                                 Uses
----------------------------------------------------------------------------------------------------------------
 
                                                  * * * * * * *
Dimethyl Sulfoxide (CAS No. 67-68-5)  For pesticide formulations used before  Solvent or co-solvent.
                                       crop emerges from soil or prior to
                                       formation of edible parts of food
                                       plants; for pesticide formulations
                                       used after crop emerges but before
                                       harvest, provided that the potential
                                       for increased residues of the
                                       formulation's active ingredient(s) in
                                       or on food commodities has been
                                       assessed.
 
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[FR Doc. 2015-25589 Filed 10-8-15; 8:45 a.m.]
 BILLING CODE 6560-50-P