[Federal Register Volume 76, Number 120 (Wednesday, June 22, 2011)]
[Rules and Regulations]
[Pages 36342-36349]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-15466]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2010-0330; FRL-8875-9]


2-methyl-2,4-pentanediol; 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 2-methyl-2,4-pentanediol (CAS Reg. No. 
107-41-5) when used as an inert ingredient as a solvent in pesticide 
formulations 40 CFR 180.910 and 180.930 for use on crops (pre-harvest 
and post-harvest) and for direct application on animals without 
limitations. 2-methyl-2,4-pentanediol is commonly referred to as 
``hexylene glycol''. The FB Sciences, Inc., 153 N. Main Street, Suite 
100, Collierville, TN 38017 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 2-methyl-2,4-pentanediol.

DATES: This regulation is effective June 22, 2011. Objections and 
requests for hearings must be received on or before August 22, 2011, 
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-2010-0330. 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: Mark Dow, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 305- 5533; 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 assist you and others in determining

[[Page 36343]]

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 site at http://www.gpoaccess.gov/ecfr.

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-2010-0330 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 
August 22, 2011. 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. Information not marked confidential pursuant to 40 CFR part 2 
may be disclosed publicly by EPA without prior notice. Submit a copy of 
your non-CBI objection or hearing request, identified by docket ID 
number EPA-HQ-OPP-2010-0330, 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 June 8, 2010 (75 FR 32466) (FRL-8827-8), 
EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C. 346a, 
announcing the filing of a pesticide petition (PP 0E7693) by FB 
Sciences, Inc., 153 N. Main Street, Ste. 100, Collierville, TN 38017. 
The petition requested that 40 CFR 180.910 and 180.930 be amended by 
establishing an exemption from the requirement of a tolerance for 
residues of 2-methyl-2,4-pentanediol (CAS Reg. No.107-41-5) when used 
as an inert ingredient as a solvent in pesticide formulations applied 
to crops pre-harvest and post-harvest and to animals without 
limitations. That notice referenced a summary of the petition prepared 
by FB Sciences, Inc., the petitioner, which is available in the docket, 
http://www.regulations.gov. There were no comments received in response 
to the notice of filing.

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 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 2-methyl-2,4-pentanediol 
including exposure resulting from the exemption established by this 
action. EPA's assessment of exposures and risks associated with 2-
methyl-2,4-pentanediol 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 2-methyl-2,4-pentanediol as well as 
the no-observed-adverse-effect-level (NOAEL) and the lowest-observed-
adverse-effect-level (LOAEL) from the

[[Page 36344]]

toxicity studies are discussed in this unit.
    2- methyl-2,4-pentanediol (CAS Reg. No. 107-41-5) is an aliphatic 
alcohol also known as: Hexylene glycol; diolane; and 1,1,3-
trimethyltrimethylene-diol. Non-pesticidal uses of 2-methyl-2,4-
pentanediol include use as a chemical intermediate, a selective solvent 
in petroleum refining, a component of hydraulic fluids, a solvent for 
inks, as an additive to cement, textile dye vehicles, a lubricant and 
fuel additive, and as an ingredient in cosmetics and hair care 
products. The Food and Drug Administration (FDA) has approved of the 
use of 2-methyl-2,4-pentanediol as an indirect food additive such as in 
adhesives in contact with food under 21 CFR parts 175-178.
    2-methyl-2,4-pentanediol is not acutely toxic to rats via the oral 
route of exposure. An Organization for Economic Cooperation and 
Development (OECD)-SIDS (2001) report indicates LD50 ranges 
from 2-4.47 g/kg. Acute dermal toxicity is low with dermal doses up to 
2,000 milligrams/kilogram (mg/kg) that did not cause death (as cited in 
OECD-SIDS, 2001). It is irritating to the skin and eyes, but not a skin 
sensitizer in guinea pigs. It has low inhalation toxicity, with an 
LC50 of 160 parts per million (ppm) (0.772 mg/L), which is 
in excess of the saturated vapor concentration.
    In a 90-day subchronic toxicity study, 2-methyl-2,4-pentanediol was 
administered by oral gavage to rats at dose levels of 50, 150, or 450 
mg/kg/bw/day. In this study the functional observational battery, blood 
chemistry, hematological parameters and histopathological examinations 
were conducted. A functional observational battery test gave no 
indication of neurotoxicity. In both sexes, hyperplasia, 
hyperkeratosis, inflammatory cell infiltration and edema of the mucosa 
and submucosa of the stomach were observed starting at 150 mg/kg/day. 
These changes were indicative of a local irritative effect resulting 
from the oral gavage procedure. Hepatocellular hypertrophy with 
increased liver weight was observed at 450 mg/kg/day in both sexes, and 
in males at 150 mg/kg/day. In the absence of degenerative or necrotic 
changes these findings were considered to be adaptive responses. At 150 
and 450 mg/kg/day, increased kidney weights and increased incidence of 
acidophilic globules in the tubular epithelium in males were suggestive 
of male rat specific alpha-2-microglobulin nephropathy, which is not 
considered as an effect relevant to humans. Observed changes were 
either fully or partially reversible over the 4-week recovery period. 
There were no adverse effects on the reproductive organs. No effects 
were observed at 50 mg/kg/day. A NOAEL of 450 mg/kg/day was determined 
for systemic toxicity because the effects described were either 
produced by irritation from the oral gavage procedure, or were 
considered adaptive responses. A range-finding 14-day study gave 
similar results.
    No guideline reproduction studies were available for assessment, 
however, no adverse effects on reproductive organs (including testes, 
prostate, seminal vesicles, epididymis, ovaries, vagina, and uterus) 
were observed in the 90-day gavage study in which rats were 
administered 2-methyl-2,4-pentanediol at doses up to 450 mg/kg/day. 
Therefore, OECD SIDS concluded that no additional studies are required 
under the SIDS program regarding fertility. EPA agrees with this 
conclusion by the OECD.
    In a developmental toxicity study, pregnant rats were administered 
30, 300, or 1,000 mg/kg/bw/day of 2-methyl-2,4-pentanediol by gavage in 
5 mL/kg of vehicle on gestation days (GD) 6-15. The NOAEL for maternal 
toxicity was 300 mg/kg/day based on a statistically significant 
reduction in group mean body weight gain and food consumption at 1,000 
mg/kg/day. There was a marginal, non-statistically significant 
reduction in fetal body weight at 1,000 mg/kg/day. Marginally higher 
incidences of fetal variations, some of which were statistically 
significant (occipitals incompletely ossified, 21.6%; extra 
thoracolumbar ribs, 18.7%; and hyoid arch not ossified, 18%), occurred 
at 1,000 mg/kg/day. A delay in the normal ossification process was also 
observed in fetuses, but this was considered by the study authors to be 
related to reduced maternal body weight gain at this dose level. The 
NOAEL and LOAEL for maternal and fetal developmental toxicity were 
determined to be 300 and 1,000 mg/kg/day, respectively.
    In another developmental toxicity study, pregnant rats received 
500, 1,200, or 1,600 mg/kg/bw/day of 2-methyl-2,4-pentanediol by gavage 
in 10 mL/kg of vehicle on GD 6-17. At 1,200 and 1,600 mg/kg/day, dams 
had ataxia and reductions in mean weight gain and food consumption. At 
the 1,600 mg/kg/day, pregnant rats had mean weight loss, and one female 
aborted prior to the end of the study. Maternal toxicity at these 
levels corresponds to decreased fetal body weights and gravid uterine 
weights. Additionally, at 1,600 mg/kg/day, there was one abortion and 
one whole litter resorption. However, the number of fetal 
malformations, such as increased incidence of skeletal variations 
(delayed ossification, extra ribs), was not significantly different 
from controls. A maternal NOAEL of 500 mg/kg/day was determined by the 
Agency, and the same NOAEL was determined in the study for fetal 
toxicity. These results support the results of a study described in 
this unit and indicate that 2-methyl-2,4-pentanediol has low potential 
for developmental toxicity.
    2-methyl-2,4-pentanediol is not genotoxic in either mammalian or 
non-mammalian cells ``in vitro.'' It was negative for mutagenicity in 
the Ames test, yeast cell assay and hamster ovary cell assay.
    Ten rats and a rabbit exposed to an aerosol of 2-methyl-2,4-
pentanediol at a concentration of 0.7 mg/L (about 145 ppm) for 7 hr/day 
for 9 days survived with mild upper respiratory irritation. No 
histopathological effects were reported.

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.
    No acute endpoint of concern was identified in the available 
toxicity studies. The endpoint of concern for the

[[Page 36345]]

chronic reference dose (cRfD) was identified from the developmental 
toxicity study in rats. In this study, the NOAEL (500 mg/kg/day) was 
based on increased incidence of clinical signs, reductions in mean body 
weight gain and food consumption seen at the LOAEL of 1,200 mg/kg/day 
and above. This NOAEL was supported by the 90-day gavage toxicity study 
in rats (NOAEL 450 mg/kg/day; highest dose tested). There was a lower 
NOAEL (300 mg/kg/day) observed in the range finding study in rats based 
on a statistically significant reduction in group mean body weight gain 
and food consumption, and marginally higher incidences of fetal 
variations seen at the LOAEL of 1,000 mg/kg/day. The differences 
between the NOAELs of the range finding study and the developmental 
toxicity study in rats were considered due to artifacts of dose 
selection. An uncertainty factor 100X (10X for intraspecies variability 
and 10X interspecies extrapolation) was applied to the NOAEL. No 
additional uncertainty factor is necessary for use of the subchronic to 
chronic study because the effects were observed at the limit dose of 
1,000 mg/kg/day and above. The FQPA factor for increased susceptibility 
of infant and children was reduced to 1X. Therefore, the cRfD is equal 
to population adjusted dose (cPAD). This endpoint and the dose was also 
used for dermal and inhalation exposure assessment for all exposure 
scenarios. Inhalation and dermal absorption was assumed to be 100%. 
This approach would provide a highly conservative estimate of risk via 
the dermal and inhalation routes of exposure.

    Table 1--Summary of Toxicological Doses and Endpoints for 2-methyl-2,4-pentanediol for Use in Human Risk
                                                   Assessment
----------------------------------------------------------------------------------------------------------------
                                     Point of departure and
         Exposure/scenario             uncertainty/safety    RfD, PAD, LOC for risk    Study and toxicological
                                             factors               assessment                  effects
----------------------------------------------------------------------------------------------------------------
Acute dietary (General population       No acute endpoint of concern was identified in the available database.
 including infants and children).
----------------------------------------------------------------------------------------------------------------
Chronic dietary (All populations)..  NOAEL = 500 mg/kg/day.  Chronic RfD = 500 mg/   Developmental Toxicity
Incidental oral short-term and       UFA = 10x.............   kg/day.                 Study--rats LOAEL = 1,200
 intermediate term.                  UFH = 10x.............  cPAD = 500 mg/kg/day..   mg/kg/day based on reduced
                                     FQPA SF = 1x..........                           body weights in maternal
                                                                                      animals, reduced fetal
                                                                                      body weights.
----------------------------------------------------------------------------------------------------------------
Dermal short and intermediate term.  100% absorption via
                                      dermal and inhalation
                                      routes; LOC MOE..
Inhalation short and intermediate    100...................
 term.
Cancer (Oral, dermal, inhalation)..     No evidence of carcinogenicity. SAR analysis negative for carcinogenic
                                       alerts. Not mutagenic in mammalian and non-mammalian mutagenicity assays.
----------------------------------------------------------------------------------------------------------------
UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members
  of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term
  study for long-term risk assessment. UFDB = to account for the absence of data or other data deficiency. FQPA
  SF = Food Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD =
  reference dose. MOE = margin of exposure. LOC = level of concern.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to 2-methyl-2,4-pentanediol, EPA considered exposure under the 
proposed exemption from the requirement of a tolerance. EPA assessed 
dietary exposures from 2-methyl-2,4-pentanediol in food as follows:
    No acute endpoint of concern was identified in the database. 
Therefore, a quantitative acute dietary exposure assessment was not 
conducted.
    i. Chronic exposure. In conducting the chronic dietary exposure 
assessments, EPA used food consumption information from the United 
States 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 2-methyl-2,4-
pentanediol. 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 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 
concentration of active ingredient in agricultural products is 
generally at least 50% 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.

[[Page 36346]]

    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% 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.
    ii. Cancer. Chronic and carcinogenicity studies were not available 
on 2-methyl-2,4-pentanediol. There is no evidence that 2-methyl-2,4-
pentanediol is carcinogenic. The Agency used a qualitative structure 
activity relationship (SAR) database, DEREK Version 11, to determine if 
there were structural alerts. No structural alerts were identified. In 
addition, it is negative for mutagenicity in mammalian and non-
mammalian mutagenicity assays. 2-methyl-2,4-pentanediol is rapidly 
metabolized and excreted as glucuronates. Based on weight-of-evidence 
and low toxicity mentioned in this unit, 2-methyl-2,4-pentanediol is 
not expected to be carcinogenic. Since the Agency has not identified 
any concerns for carcinogenicity relating to 2-methyl-2,4-pentanediol, 
a dietary exposure assessment to evaluate cancer risk was not 
performed.
    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 2-methyl-2,4-
pentanediol, a conservative drinking water concentration value of 100 
ppb 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). No 
residential uses as a pesticide inert ingredient have been requested 
and none are expected. Although 2-methyl-2,4-pentanediol is used in 
cosmetics and hair care products, the Agency believes exposure and risk 
from these routes of exposure to be negligible. The FDA includes 2-
methyl-2,4-pentanediol (i.e., hexylene glycol) in its list of Indirect 
Additives Used in Food Contact Subtances. The exposure to 2-methyl-2,4-
pentanediol through hair color use is considered minimal because it is 
a volatile chemical, treatment times are very short and absorption 
through the scalp is limited. Based on these considerations, the Agency 
concluded that there is no need to conduct aggregate exposure through 
use of consumer products. Further, there are no reliable data with 
which to estimate such exposures.
    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 2-methyl-2,4-pentanediol to share a common 
mechanism of toxicity with any other substances, and 2-methyl-2,4-
pentanediol does not appear to produce a toxic metabolite produced by 
other substances. For the purposes of this tolerance action, therefore, 
EPA has assumed that 2-methyl-2,4-pentanediol 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 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. The maternal and 
developmental effects were only observed at the limit dose of 1,000 mg/
kg/day and above in the developmental toxicity study in rats. Maternal 
and fetal toxicity were mainly manifested as decreases in body weights. 
Marginally higher incidences of fetal variations were also observed at 
the limit dose or above. There were no guideline reproduction studies 
available on 2-methyl-2,4-pentanediol; however, no adverse effects on 
reproductive organs (including testes, prostate, seminal vesicles, 
epididymis, ovaries, vagina, and uterus) were observed at doses up to 
450 mg/kg/day in a 90-day toxicity study in rats. In addition, the 
reproductive indices were not affected in the two available 
developmental toxicity studies in rats.
    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 2-methyl-2,4-pentanediol is not 
complete but considered as adequate for FQPA assessment given the low 
toxicity of 2-methyl-2,4-pentanediol. No guideline reproduction studies 
were available for assessment; however, no adverse effects on 
reproductive organs (including testes, prostate, seminal vesicles, 
epididymis, ovaries, vagina, and uterus) were observed in the 90-day 
gavage study in which rats were administered 2-methyl-2,4-pentanediol 
at doses up to 450 mg/kg/day. Therefore, OECD SIDS concluded that no 
additional studies are required under the SIDS program regarding 
fertility. EPA is in agreement

[[Page 36347]]

with the OECD conclusion. Chronic studies are also not available, but 
the concern for chronic toxicity is low given the low toxicity of 2-
methyl-2,4-pentanediol.
    ii. No evidence of clinical signs of neurotoxicity was observed in 
the available database. No evidence of neurobehavioral or 
neuropathology was seen in a 90-day toxicity study in rats. There is no 
indication that 2-methyl-2,4-pentanediol is a neurotoxic chemical and 
there is no need for a developmental neurotoxicity study or additional 
UFs to account for neurotoxicity.
    iii. There is no evidence that 2-methyl-2,4-pentanediol results in 
increased susceptibility in rats (as described in this unit).
    iv Immunotoxicity studies for 2-methyl-2,4-pentanediol were not 
available for review. However, there was no evidence of immunotoxicity 
in the available database.
    v. There are no residual uncertainties identified in the exposure 
databases. The dietary food exposure assessments were performed based 
on 100 percent crop treated (PCT) and tolerance-level residues. EPA 
made conservative (protective) assumptions in the ground and surface 
water modeling used to assess exposure to 2-methyl-2,4-pentanediol in 
drinking water. These assessments will not underestimate the exposure 
and risks posed by 2-methyl-2,4-pentanediol.

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 (aPAD) and chronic (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, 
2-methyl-2,4-pentanediol 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 
2-methyl-2,4-pentanediol from food and water will utilize 3.8% of the 
cPAD for the U.S. population and Children 1-2 yrs of age 12.5% cPAD, 
the population group receiving the greatest exposure. Based on the 
explanation in this unit, regarding residential use patterns, chronic 
residential exposure to residues of 2-methyl-2,4-pentanediol 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).
    A short-term adverse effect was identified; however, 2-methyl-2,4-
pentanediol is not currently used as an inert ingredient in pesticide 
products that are registered for any use patterns that would result in 
short-term residential exposure. Short-term risk is assessed based on 
short-term residential exposure plus chronic dietary exposure. Because 
there is no short-term residential exposure resulting from use as an 
inert ingredient in pesticidal formulations and chronic dietary 
exposure has already been assessed under the appropriately protective 
cPAD (which is at least as protective as the POD used to assess short-
term risk), no further assessment of short-term risk is necessary, and 
EPA relies on the chronic dietary risk assessment for evaluating short-
term risk for 2-methyl-2,4-pentanediol.
    For the reasons discussed in Unit IV.C.3., short-term aggregate 
exposure assessment was not conducted for non-pesticidal uses.
    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). An intermediate-term adverse effect was identified; however, 2-
methyl-2,4-pentanediol is not currently used as an inert ingredient in 
pesticide products that are registered for any use patterns that would 
result in intermediate-term residential exposure. Intermediate-term 
risk is assessed based on intermediate-term residential exposure plus 
chronic dietary exposure. Because there is no intermediate-term 
residential exposure and chronic dietary exposure has already been 
assessed under the appropriately protective cPAD (which is at least as 
protective as the POD used to assess intermediate-term risk), no 
further assessment of intermediate-term risk is necessary, and EPA 
relies on the chronic dietary risk assessment for evaluating 
intermediate-term risk for 2-methyl-2,4-pentanediol. For the reasons 
discussed in Unit IV.C.3., intermediate term aggregate exposure 
assessment was not conducted for non-pesticidal uses.
    5. Aggregate cancer risk for U.S. population. 2-methyl-2,4-
pentanediol is not expected to pose a cancer risk to humans. Therefore, 
aggregate cancer risk was not performed.
    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 2-methyl-2,4-pentanediol 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

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international maximum residue limits (MRLs) established 
by the Codex Alimentarius Commission (Codex), as required by FFDCA 
section 408(b)(4). The Codex Alimentarius is a joint U.N. Food and 
Agriculture Organization/World Health Organization food standards 
program, and it is recognized as an international food safety 
standards-setting organization in trade agreements to which the United 
States is a party. EPA may establish a tolerance that is different from 
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain 
the reasons for departing from the Codex level.
    The Codex has not established a MRL for 2-methyl-2,4-pentanediol.

VI. Conclusions

    Therefore, an exemption from the requirement of a tolerance is 
established under 40 CFR 180.910 and Sec.  180.930 for 2-methyl-2,4-
pentanediol. (CAS Reg. No. 107-1-41-5) when used as an inert ingredient 
in pesticide formulations applied to crops and food animals without 
limitations.

VII. Statutory and Executive Order Reviews

    This final rule establishes 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

[[Page 36348]]

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 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 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) (Pub. L. 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).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: June 10, 2011.
Lois Rossi,
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.  180.910, the table is amended by adding alphabetically the 
following inert ingredients to read as follows:


Sec.  180.910  Insert ingredients used pre-harvest and post-harvest; 
exemptions from the requirement of a tolerance.

* * * * *

------------------------------------------------------------------------
        Inert ingredients               Limits               Uses
------------------------------------------------------------------------
 
                              * * * * * * *
2-methyl-2,4-pentanediol (CAS     Without limitation  Growing crops and
 Reg..                                                 food animals
No.-107-41-5)...................
 
                              * * * * * * *
------------------------------------------------------------------------


0
3. In Sec.  180.930, the table is amended by adding alphabetically the 
following inert ingredients to read as follows:


Sec.  180.930  Insert ingredients applied to animals: exemption from 
the requirement of a tolerance.

* * * * *

------------------------------------------------------------------------
        Inert ingredients               Limits               Uses
------------------------------------------------------------------------
 
                              * * * * * * *
2-methyl-2,4-pentanediol (CAS     Without limitation  Growing crops and
 Reg. No.-107-41-5).                                   food animals
 
                              * * * * * * *
------------------------------------------------------------------------


[[Page 36349]]

[FR Doc. 2011-15466 Filed 6-21-11; 8:45 am]
BILLING CODE 6560-50-P