[Federal Register Volume 71, Number 234 (Wednesday, December 6, 2006)]
[Proposed Rules]
[Pages 70703-70709]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-20648]


-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2006-0731; FRL-8104-1]


Diphenylamine; Proposed Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

-----------------------------------------------------------------------

SUMMARY: This document proposes to establish a tolerance for residues 
of diphenylamine in or on pear under the Federal Food, Drug, and 
Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act of 
1996 (FQPA).

DATES: Comments must be received on or before February 5, 2007.

ADDRESSES: Submit your comments, identified by docket identification 
(ID) number EPA-HQ-OPP-2006-0731, 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 
Building), 2777 S. Crystal Drive, Arlington, VA. Deliveries are only 
accepted during the Docket'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 telephone number is (703) 305-5805.
    Instructions: Direct your comments to docket ID number EPA-HQ-OPP-
2006-0731. EPA's policy is that all comments received will be included 
in the docket without change and may be made available on-line at 
http://www.regulations.gov, including any personal information 
provided, unless the comment includes information claimed to be 
Confidential Business Information (CBI) or other information whose 
disclosure is restricted by statute. Do not submit information that you 
consider to be CBI or otherwise protected through regulations.gov or e-
mail. The Federal regulations.gov website is an ``anonymous access'' 
system, which means EPA will not know your identity or contact 
information unless you provide it in the body of your comment. If you 
send an e-mail comment directly to EPA without going through 
regulations.gov, your e-mail address will be automatically captured and 
included as part of the comment that is placed in the docket and made 
available on the Internet. If you submit an electronic comment, EPA 
recommends that you include your name and other contact information in 
the body of your comment and with any disk or CD-ROM you submit. If EPA 
cannot read your comment due to technical difficulties and cannot 
contact you for clarification, EPA may not be able to consider your 
comment. Electronic files should avoid the use of special characters, 
any form of encryption, and be free of any defects or viruses.
    Docket: All documents in the docket are listed in the docket index. 
Although listed in the index, some information is not publicly 
available, e.g., CBI or other information whose disclosure is 
restricted by statute. Certain other material, such as copyrighted 
material, is not placed on the Internet and will be publicly available 
only in hard copy form. Publicly available docket materials are 
available either 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 
Building), 2777 S. Crystal Drive, Arlington, VA. The hours of operation 
of this Docket Facility are from 8:30 a.m. to 4 p.m., Monday through 
Friday, excluding legal holidays. The Docket telephone number is (703) 
305-5805.

FOR FURTHER INFORMATION CONTACT: Shaja R. Brothers, Registration 
Division (7505P), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave, NW., Washington, DC 20460-
0001; telephone number: (703) 308-3194; e-mail address: 
[email protected].



[[Page 70704]]

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 
whether this action might apply to certain entities. To determine 
whether you or your business may be affected by this action, you should 
carefully examine the applicability provisions. 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. What Should I Consider as I Prepare My Comments for EPA?

    1. Submitting CBI. Do not submit this information to EPA through 
www.regulations.gov or e-mail. Clearly mark the part or all of the 
information that you claim to be CBI. For CBI information in a disk or 
CD ROM that you mail to EPA, mark the outside of the disk or CD ROM as 
CBI and then identify electronically within the disk or CD ROM the 
specific information that is claimed as CBI. In addition to one 
complete version of the comment that includes information claimed as 
CBI, a copy of the comment that does not contain the information 
claimed as CBI must be submitted for inclusion in the public docket. 
Information so marked will not be disclosed except in accordance with 
procedures set forth in 40 CFR part 2.
    2. Tips for preparing your comments. When submitting comments, 
remember to:
    i. Identify the document by docket ID number and other identifying 
information (subject heading, Federal Register date and page number).
    ii. Follow directions. The Agency may ask you to respond to 
specific questions or organize comments by referencing a Code of 
Federal Regulations (CFR) part or section number.
    iii. Explain why you agree or disagree; suggest alternatives and 
substitute language for your requested changes.
    iv. Describe any assumptions and provide any technical information 
and/or data that you used.
    v. If you estimate potential costs or burdens, explain how you 
arrived at your estimate in sufficient detail to allow for it to be 
reproduced.
    vi. Provide specific examples to illustrate your concerns and 
suggest alternatives.
    vii. Explain your views as clearly as possible, avoiding the use of 
profanity or personal threats.
    viii. Make sure to submit your comments by the comment period 
deadline identified.

II. Background and Statutory Findings

    EPA on its own initiative, under section 408(e) of the FFDCA, 21 
U.S.C. 346a(e), is proposing to establish a tolerance for residues of 
the fungicide, diphenylamine in or on pear at 5.0 parts per million 
(ppm). The Interregional Research Project Number 4 (IR-4) submitted a 
petition (PP 0E6107) for this use. However, neither IR-4 nor Atomchem 
North American Incorporated, the registrant, submitted all required 
elements of a petition in support of establishing a tolerance. Because 
the petition was incomplete, EPA did not publish a Notice of Filing for 
the petition.
    Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish 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 the 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 the FFDCA requires EPA to give special 
consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical residue. . . 
.''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. For further discussion of the 
regulatory requirements of section 408 of the FFDCA and a complete 
description of the risk assessment process, see http://www.epa.gov/fedrgstr/EPA-PEST/1997/November/Day-26/p30948.htm.

III. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D) of the FFDCA, EPA has reviewed 
the available scientific data and other relevant information in support 
of this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure, consistent with section 
408(b)(2) of the FFDCA, for a tolerance for residues of diphenylamine 
on pear at 5.0 ppm. EPA's assessment of exposures and risks associated 
with establishing the tolerance follows:

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children. The nature of the toxic effects caused by diphenylamine is 
discussed in Table 1 of this unit as well as the no-observed-adverse-
effect-level (NOAEL) and the lowest-observed-adverse-effect-level 
(LOAEL) from the toxicity studies reviewed.

[[Page 70705]]



                                Table 1.--Subchronic, Chronic, and Other Toxicity
----------------------------------------------------------------------------------------------------------------
             Guideline No.                       Study Type                            Results
----------------------------------------------------------------------------------------------------------------
870.3100                                 90-Day oral toxicity        NOAEL = 75 mg/kg/day
                                          rodents                    LOAEL = 375 mg/kg/day based on decreased
                                                                      body weight and body weight gain, dark
                                                                      urine, increased absolute spleen and liver
                                                                      weights, congestion in spleen, kidney, and
                                                                      liver, discoloration and alterations in
                                                                      hematological and clinical chemistry
                                                                      parameters.
----------------------------------------------------------------------------------------------------------------
870.3100                                 90-Day oral toxicity        NOAEL = 2 mg/kg/day
                                          rodents                    M/F LOAEL = 94/107 mg/kg/day based on liver/
                                                                      spleen alterations (extramedullary
                                                                      hematopoiesis in the liver, discoloration
                                                                      and hemosiderosis of the liver, congestion
                                                                      and extramedullary hematopoiesis in the
                                                                      spleen).
----------------------------------------------------------------------------------------------------------------
870.3150                                 90-Day oral toxicity non-   M/F NOAEL = 50 mg/kg/day
                                          rodents                    LOAEL (mg/kg/day) not determined
----------------------------------------------------------------------------------------------------------------
870.3200                                 21/28-Day dermal toxicity   NOAEL = 500 mg/kg/day
                                                                     LOAEL = 1,000 mg/kg/day based on effects in
                                                                      the stomach (dark foci-red foci in both
                                                                      sexes-6/10).
                                                                     Dermal: NOAEL = 1,000 mg/kg/day;
                                                                     LOAEL (mg/kg/day): Not determined.
----------------------------------------------------------------------------------------------------------------
870.3700                                 Prenatal developmental in   Maternal NOAEL = 50 mg/kg/day
                                          rodents                    Maternal LOAEL = 100 mg/kg/daybased on
                                                                      decreased spleen weights and discoloration
                                                                      of the spleen
                                                                     Developmental NOAEL = 100 mg/kg/day
                                                                     Developmental LOAEL (mg/kg/day): Not
                                                                      determined
----------------------------------------------------------------------------------------------------------------
870.3700                                 Prenatal developmental in   Maternal NOAEL = 100 mg/kg/day
                                          nonrodents                 Maternal LOAEL = 300 mg/kg/daybased on
                                                                      deceased body weight gains andfood
                                                                      consumption
                                                                     Developmental NOAEL = 300 mg/kg/day
                                                                     Developmental LOAEL (mg/kg/day): Not
                                                                      determined
----------------------------------------------------------------------------------------------------------------
870.3800                                 Reproduction and fertility  Parental/Systemic NOAEL (mg/kg/day): Not
                                          effects                     determined.
                                                                     Parental/Systemic M/F LOAEL = 40/46 mg/kg/
                                                                      day based on gross pathological findings
                                                                      in the spleen and microscopic findings in
                                                                      the kidney, liver, and spleen.
                                                                     Reproductive M/F NOAEL = 115/131 mg/kg/day.
                                                                     Reproductive M/F LOAEL = 399/448 mg/kg/day
                                                                      based on decreased litter size in both
                                                                      generations.
                                                                     Offspring M/F NOAEL = 40/46 mg/kg/day.
                                                                     Offspring M/F LOAEL = 115/131 mg/kg/day
                                                                      based on decreased body weight of F2 pups
                                                                      in late lactation.
----------------------------------------------------------------------------------------------------------------
870.4100                                 Chronic toxicity dogs       NOAEL = 10 mg/kg/day
                                                                     LOAEL = 50 mg/kg/day based on alterations
                                                                      in clinical chemistry parameters
                                                                      (increased BUN, cholesterol, total
                                                                      bilirubin) and increased absolute/relative
                                                                      kidney, liver and spleen weights.
----------------------------------------------------------------------------------------------------------------
870.4200                                 Carcinogenicity rats        NOAEL (mg/kg/day): Not determined.
                                                                     M/F LOAEL = 73/91 mg/kg/day based on
                                                                      histopathological lesions in the spleen.
                                                                      No evidence of carcinogenicity.
----------------------------------------------------------------------------------------------------------------
870.4300                                 Carcinogenicity mice        M/F NOAEL = 29/25 mg/kg/day.
                                                                     M/F LOAEL = 147/138 mg/kg/day based on
                                                                      reduced body weight and body weight gains,
                                                                      changes in hematological parameters,
                                                                      spleen and kidney lesions and increased
                                                                      clinical signs of toxicity. No evidence of
                                                                      carcinogenicity
----------------------------------------------------------------------------------------------------------------
870.5100                                 Gene mutation               Negative
----------------------------------------------------------------------------------------------------------------
870.5300                                 Cytogenetics                Weakly mutagenic in the presence of
                                                                      metabolic activation
----------------------------------------------------------------------------------------------------------------
870.5395                                 Other effects               Negative
----------------------------------------------------------------------------------------------------------------

[[Page 70706]]

 
870.7485                                 Metabolism and              Terminal distribution data showed no
                                          pharmacokinetics            significant residual activity in tissues
                                                                      168 hours post-dose for both the low and
                                                                      high oral dose groups: Urine was the major
                                                                      route for excretion.
                                                                     Recovery after 168 hours: Single/repeated
                                                                      low dose = urine 68-81% (both sexes)
                                                                      single high dose = 73-74%
                                                                     Male rats excreted a greater percentage of
                                                                      diphenylamine derived activity at the low
                                                                      dose, while female rats showed greater
                                                                      excretion in feces at this dose. At the
                                                                      high dose, the percentage eliminated in
                                                                      urine was equivalent in both males and
                                                                      females.
                                                                     Metabolites-urine: Dihydroxylated
                                                                      conjugates of diphenylamine, mono-
                                                                      hydroxylated sulfate conjugates of
                                                                      diphenylamine, monohydroxylated
                                                                      glucuronide conjugates of diphenylamine.
                                                                     Metabolites-feces: Parent chemical and 4-
                                                                      hydroxydiphenylamine, which comprised 0.5-
                                                                      3% administered dose in both sexes.
----------------------------------------------------------------------------------------------------------------

B. Toxicological Endpoints

    The dose at which no adverse effects are observed (the NOAEL) from 
the toxicology study identified as appropriate for use in risk 
assessment is used to estimate the toxicological level of concern 
(LOC). However, the lowest dose at which adverse effects of concern are 
identified (the LOAEL) is sometimes used for risk assessment if no 
NOAEL was achieved in the toxicology study selected. An uncertainty 
factor (UF) is applied to reflect uncertainties inherent in the 
extrapolation from laboratory animal data to humans and in the 
variations in sensitivity among members of the human population as well 
as other unknowns. An UF of 100 is routinely used, 10X to account for 
interspecies differences and 10X for intra species differences.
    For dietary risk assessment (other than cancer) the Agency uses the 
UF to calculate an acute or chronic reference dose (acute RfD or 
chronic RfD) where the RfD is equal to the NOAEL divided by the 
appropriate UF (RfD = NOAEL/UF). Where an additional safety factor is 
retained due to concerns unique to the FQPA, this additional factor is 
applied to the RfD by dividing the RfD by such additional factor. The 
acute or chronic Population Adjusted Dose (aPAD or cPAD) is a 
modification of the RfD to accommodate this type of FQPA Safety Factor 
(SF).
    For non-dietary risk assessments (other than cancer) the UF is used 
to determine the LOC. For example, when 100 is the appropriate UF (10X 
to account for interspecies differences and 10X for intraspecies 
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to 
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and 
compared to the LOC.
    The linear default risk methodology (Q*) is the primary method 
currently used by the Agency to quantify carcinogenic risk. The Q* 
approach assumes that any amount of exposure will lead to some degree 
of cancer risk. A Q* is calculated and used to estimate risk which 
represents a probability of occurrence of additional cancer cases 
(e.g., risk is expressed as 1 x 10\6\ or one in a million). Under 
certain specific circumstances, MOE calculations will be used for the 
carcinogenic risk assessment. In this non-linear approach, a ``point of 
departure'' is identified below which carcinogenic effects are not 
expected. The point of departure is typically a NOAEL based on an 
endpoint related to cancer effects though it may be a different value 
derived from the dose response curve. To estimate risk, a ratio of the 
point of departure to exposure (MOEcancer = point of 
departure/exposures) is calculated. A summary of the toxicological 
endpoints for diphenylamine used for human risk assessment is shown in 
Table 2 of this unit:

    Table 2.--Summary of Toxicological Dose and Endpoints for Diphenylamine for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                                                 FQPA SF* and Level of
          Exposure Scenario               Dose Used in Risk         Concern for Risk     Study and Toxicological
                                            Assessment, UF             Assessment                Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary (Females 13-50 years of  N/A                      N/A                      An acute reference dose
 age)                                                                                     for females aged 13-50
                                                                                          has not been
                                                                                          established.
                                                                                          Developmental toxicity
                                                                                          studies in rats and
                                                                                          rabbits and a 2-
                                                                                          generation
                                                                                          reproduction study in
                                                                                          rats did not
                                                                                          demonstrate evidence
                                                                                          of toxicity
                                                                                          attributable to a
                                                                                          single dose.
----------------------------------------------------------------------------------------------------------------
Acute Dietary (General population      N/A                      N/A                      An endpoint
 including infants and children)                                                          attributable to a
                                                                                          single dose was not
                                                                                          identified from the
                                                                                          available database.
----------------------------------------------------------------------------------------------------------------
Chronic Dietary (All populations)      NOAEL = 10 mg/kg/day     FQPA SF = 1X             Chronic Toxicity - Dog
                                       UF = 100 Chronic RfD =   cPAD = chronic RfD/FQPA  LOAEL = 50 mg/kg/day
                                        0.1 mg/kg/day.           SF = 0.1 mg/kg/day.      based on alterations
                                                                                          in clinical chemistry
                                                                                          parameters (increased
                                                                                          BUN, cholesterol,
                                                                                          total bilirubin) and
                                                                                          increased absolute/
                                                                                          relative kidney,
                                                                                          liver, and spleen
                                                                                          weights.
----------------------------------------------------------------------------------------------------------------

[[Page 70707]]

 
Short-Term Dermal (1 to 30 days)       Dermal (or oral) study   LOC for MOE = 100        21-Day Dermal - Rabbit
(Residential)........................  NOAEL= 500 mg/kg/day...  (Residential)..........  LOAEL = 1,000 mg/kg/day
                                                                                          based on effects in
                                                                                          the stomach (dark red
                                                                                          foci in both sexes).
----------------------------------------------------------------------------------------------------------------
Intermediate-Term Dermal (1 week to    Dermal (or oral) study   LOC for MOE = 100        21-Day Dermal- Rabbit
 several months)                        NOAEL = 500 mg/kg/day   (Residential)..........  LOAEL = 1,000 mg/kg/day
(Residential)........................                                                     based on effects in
                                                                                          the stomach (dark red
                                                                                          foci in both sexes).
----------------------------------------------------------------------------------------------------------------
Short-Term Inhalation (1 to 30 days)   Inhalation (or oral)     LOC for MOE = 100        Developmental Toxicity
(Residential)........................   study                   (Residential)..........    Rat
                                       NOAEL = 50 mg/kg/day                              LOAEL = 100 mg/kg/day
                                        (inhalation absorption                            based on increased
                                        rate = 100%).                                     spleen weights and
                                                                                          discoloration of the
                                                                                          spleen.
----------------------------------------------------------------------------------------------------------------
Intermediate-Term Inhalation (1 week   Inhalation (or oral)     LOC for MOE = 100        Developmental Toxicity
 to several months)                     study                   (Residential)..........    Rat
(Residential)........................  NOAEL = 50 mg/kg/day                              LOAEL = 100 mg/kg/day
                                        (inhalation absorption                            based on increased
                                        rate = 100%).                                     spleen weights and
                                                                                          discoloration of the
                                                                                          spleen.
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation)      N/A                      N/A                      Classification: This
                                                                                          chemical is ``not
                                                                                          likely'' to be a human
                                                                                          carcinogen.
----------------------------------------------------------------------------------------------------------------

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. The residue of concern 
in plants and livestock for the tolerance enforcement and risk 
assessment is parent diphenylamine. Tolerances are established in 40 
CFR 180.190(a) for diphenylamine residues in/on apple at 10 ppm and 
apple, wet pomace at 30 ppm. Diphenylamine (EC or SC/L) is applied to 
apples (pre- or post-harvest) as a spray, dip or drench application. 
Additionally, tolerances are established at 0.01 ppm in milk, meat, 
fat, and meat byproducts (except liver) of cattle, goat, horse, and 
sheep, and at 0.1 ppm in liver of these animals. Risk assessments were 
conducted by EPA to assess dietary exposures from diphenylamine in food 
as follows:
    i. Acute exposure. There were no toxic effects attributable to a 
single dose. An endpoint of concern was not identified to quantitate an 
acute-dietary risk to the U.S. general population or to the 
subpopulation females 13-50 years old. Therefore, an acute aggregate 
exposure assessment was not performed.
    ii. Chronic exposure.In conducting this chronic dietary risk 
assessment the Dietary Exposure Evaluation Model (DEEM\TM\) analysis 
evaluated the individual food consumption as reported by respondents in 
the USDA 1994-1996 and 1998 Nationwide Continuing Surveys of Food 
Intake by Individuals (CSFII) and accumulated exposure to the chemical 
for each commodity. The following assumptions were made for the chronic 
exposure assessments: The chronic dietary exposure analysis was based 
on tolerance level residues, DEEM (Version 7.81) default processing 
factors, an empirical processing factor for apple juice, and 100% crop 
treated assumptions.
    iii. Cancer. Diphenylamine was classified as ``not likely to be a 
human carcinogen;'' therefore, a cancer dietary exposure analysis was 
not performed.
    2. Dietary exposure from drinking water. Diphenylamine uses are 
post-harvest; therefore, residues in drinking water are not relevant to 
this risk assessment.
    3. Dietary exposure from non-dietary exposure. Diphenylamine is not 
registered for use on any sites that would result in residential 
exposure. Therefore a residential exposure risk assessment was not 
performed.
    4. Cumulative effects from substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of the 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.''
    Unlike other pesticides for which EPA has followed a cumulative 
risk approach based on a common mechanism of toxicity, EPA has not made 
a common mechanism of toxicity finding as to diphenylamine and any 
other substances and diphenylamine does not appear to produce a toxic 
metabolite produced by other substances. For the purposes of this 
tolerance action, therefore, EPA has not assumed that diphenylamine has 
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 the policy statements released by EPA's Office of 
Pesticide Programs concerning common mechanism determinations and 
procedures for cumulating effects from substances found to have a 
common mechanism on EPA's website at http://www.epa.gov/pesticides/cumulative/.

D. Safety Factor for Infants and Children

    1. In general. Section 408 of the FFDCA provides that EPA shall 
apply an additional tenfold 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 data base on toxicity and exposure 
unless EPA determines that a different margin of safety will be safe 
for infants and children. Margins of safety are incorporated into EPA 
risk assessments either directly through use of a MOE analysis or 
through using uncertainty (safety) factors in calculating a dose level 
that poses no appreciable risk to humans.
    2. Prenatal and postnatal sensitivity. There is no indication of 
increased sensitivity of rats or rabbits to in utero and postnatal 
exposure to diphenylamine. In prenatal

[[Page 70708]]

developmental toxicity studies in rats and rabbits, no evidence of 
developmental toxicity was observed. In a 2-generation reproduction 
study, offspring toxicity (decreased body weight) was seen only in the 
presence of maternal toxicity.
    3. Conclusion. EPA recommended the FQPA safety factor be reduced to 
1X for the following reasons:
    i. There is a complete toxicity data base for diphenylamine;
    ii. The toxicity database showed no increase in susceptibility in 
fetuses and pups with in utero and postnatal exposure, and
    iii. The dietary food exposure assessment is based on recommended 
tolerance-level residues (except those processed commodities for which 
processing factors were used) and assumes 100% crop treated for all 
commodities, which resulted in very high-end estimates of dietary 
exposure.

E. Aggregate Risks and Determination of Safety

    1. Acute risk. There were no toxic effects attributable to a single 
dose. An endpoint of concern was not identified to quantitate an acute-
dietary risk to the U.S. general population or to the subpopulation 
females 13-50 years old. Therefore, diphenylamine 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 exposure to 
diphenylamine from food will utilize 12% of the cPAD for the U.S. 
population, 69% of the cPAD for all infants <1 year old, and 90% of the 
cPAD for children 1-2 years old. There are no residential uses for 
diphenylamine that result in chronic residential exposure. In addition, 
there is no potential for chronic dietary exposure in drinking water as 
diphenylamine is applied only as a post-harvest use. Therefore, EPA 
does not expect the aggregate exposure to exceed 100% of the cPAD.
    3. Short and intermediate-term risk. There are no residential uses 
for diphenylamine, and residues are not expected to occur in drinking 
water. Therefore, short and intermediate-term aggregate risk 
assessments were not performed.
    4. Aggregate cancer risk for U.S. population. Diphenylamine is not 
likely to be carcinogenic to humans. Therefore, a cancer aggregate risk 
assessment was not performed.
    5. 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, and to infants and children from aggregate 
exposure to diphenylamine residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    An adequate gas chromatography/mass-selective detector (GC/MSD) 
method is available for enforcing tolerances on apple commodities, and 
this method was used for data collection in the current post-harvest 
study. The method was adequately validated in conjunction with the 
sample analyses. A modification of this method was used in the pear 
analyses. Therefore, the Agency requires the registrant to submit an 
analytical reference standard of diphenylamine to the EPA National 
Pesticide Standards Repository. The method may be requested from: 
Chief, Analytical Chemistry Branch, Environmental Science Center, 701 
Mapes Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-2905; 
e-mail address: [email protected].

B. International Residue Limits

    Codex MRLs have been established for the post harvest use of 
diphenylamine on pears. The MRL for pear is 5 ppm, and is the same as 
the recommended pear tolerance.

V. Conclusion

    A tolerance is proposed for residues of diphenylamine in pear at 
5.0 ppm.

VI. Statutory and Executive Order Reviews

    This proposed rule establishes a tolerance under section 408(d) of 
the 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 proposed rule has 
been exempted from review under Executive Order 12866 due to its lack 
of significance, this proposed rule is not subject to Executive Order 
13211, Actions Concerning Regulations That Significantly Affect Energy 
Supply, Distribution, or Use (66 FR 28355, May 22, 2001). This proposed 
rule does not contain any information collections subject to OMB 
approval under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et 
seq., or 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). 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); or OMB review or any 
Agency action under Executive Order 13045, entitled Protection of 
Children from Environmental Health Risks and Safety Risks (62 FR 19885, 
April 23, 1997). 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). Pursuant to the Regulatory Flexibility Act (RFA) 
(5 U.S.C. 601 et seq.), the Agency hereby certifies that this proposed 
action will not have significant negative economic impact on a 
substantial number of small entities. Establishment of a tolerance 
legalizes the presence of a pesticide residue in a food. In addition, 
the Agency has determined that this action will not have a substantial 
direct effect on States, on the relationship between the national 
government and the States, or on the distribution of power and 
responsibilities among the various levels of government, as specified 
in Executive Order 13132, entitled Federalism (64 FR 43255, August 10, 
1999). Executive Order 13132 requires EPA to develop an accountable 
process to ensure ``meaningful and timely input by State and local 
officials in the development of regulatory policies that have 
federalism implications.'' ``Policies that have federalism 
implications'' is defined in the Executive order to include regulations 
that have ``substantial direct effects on the States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government.'' This proposed rule directly regulates growers, food 
processors, food handlers and food retailers, not States. This action 
does not alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of the FFDCA. For these same reasons, the Agency 
has determined that this proposed rule does not have any ``tribal 
implications'' as described in Executive Order 13175, entitled 
Consultation and Coordination with Indian Tribal Governments (65 FR 
67249, November 6, 2000). Executive Order 3175, requires EPA to develop 
an accountable process to ensure ``meaningful and timely input by 
tribal officials in the development of regulatory policies that have 
tribal implications.'' ``Policies that have tribal implications'' is 
defined in the

[[Page 70709]]

Executive order to include regulations that have ``substantial direct 
effects on one or more Indian tribes, on the relationship between the 
Federal Government and the Indian tribes, or on the distribution of 
power and responsibilities between the Federal Government and Indian 
tribes.'' This proposed rule will not have substantial direct effects 
on tribal governments, on the relationship between the Federal 
Government and Indian tribes, or on the distribution of power and 
responsibilities between the Federal Government and Indian tribes, as 
specified in Executive Order 13175. Thus, Executive Order 13175 does 
not apply to this proposed rule.

List of Subjects in 40 CFR Part 180

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

    Dated: November 22, 2006.
Donald R. Stubbs,
Acting Director, Registration Division, Office of Pesticide Programs.
    Therefore, it is proposed that 40 CFR chapter I be amended as 
follows:

PART 180--AMENDED

    1. The authority citation for part 180 continues to read as 
follows:

    Authority: 21 U.S.C. 321(q), 346a and 371.
    2. Section 180.190 is amended by alphabetically adding a commodity 
to the table in paragraph (a) to read as follows:


Sec.  180.190  Diphenylamine; tolerances for residues.

    (a) * * *

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
                                * * * * *
Pear (post harvest)........................................          5.0
                                * * * * *
------------------------------------------------------------------------

[FR Doc. E6-20648 Filed 12-5-06; 8:45 am]
BILLING CODE 6560-50-S