Streptomycin; Pesticide Tolerances for Emergency Exemptions, 29049-29055 [2013-11858]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[Federal Register Volume 78, Number 96 (Friday, May 17, 2013)]
[Rules and Regulations]
[Pages 29049-29055]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-11858]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2011-0852; FRL-9385-3]


Streptomycin; Pesticide Tolerances for Emergency Exemptions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes time-limited tolerances for 
residues of streptomycin in or on grapefruit and grapefruit, dried 
pulp. This action is in response to EPA's granting of an emergency 
exemption under the Federal Insecticide, Fungicide, and Rodenticide Act 
(FIFRA) authorizing use of the pesticide on grapefruit. This regulation 
establishes maximum permissible levels for residues of streptomycin in 
or on these commodities. The time-limited tolerances expire on December 
31, 2015.

DATES: This regulation is effective May 17, 2013. Objections and 
requests for hearings must be received on or before July 16, 2013 and 
must be filed in accordance with the instructions provided in 40 CFR 
part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: The docket for this action, identified by docket 
identification (ID) number EPA-HQ-OPP-2011-0852, is available at https://www.regulations.gov or at the Office of Pesticide Programs Regulatory 
Public Docket (OPP Docket) in the Environmental Protection Agency 
Docket Center (EPA/DC), EPA West Bldg., Rm. 3334, 1301 Constitution 
Ave. NW., Washington, DC 20460-0001. The Public Reading Room is open 
from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal 
holidays. The telephone number for the Public Reading Room is (202) 
566-1744, and the telephone number for the OPP Docket is (703) 305-
5805. Please review the visitor instructions and additional information 
about the docket available at https://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Andrea Conrath, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone 
number: (703) 308-9356; email address: conrath.andrea@epa.gov.

[[Page 29050]]


SUPPLEMENTARY INFORMATION: 

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
The following list of North American Industrial Classification System 
(NAICS) codes is not intended to be exhaustive, but rather provides a 
guide to help readers determine whether this document applies to them. 
Potentially affected entities may include:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).

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 https://ecfr.gpoaccess.gov/cgi/t/text/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

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

    Under section 408(g) of the Federal Food, Drug, and Cosmetic Act 
(FFDCA), 21 U.S.C. 346a, any person may file an objection to any aspect 
of this regulation and may also request a hearing on those objections. 
You must file your objection or request a hearing on this regulation in 
accordance with the instructions provided in 40 CFR part 178. To ensure 
proper receipt by EPA, you must identify docket ID number EPA-HQ-OPP-
2011-0852 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 July 16, 2013. Addresses for 
mail and hand delivery of objections and hearing requests are provided 
in 40 CFR 178.25(b).
    In addition to filing an objection or hearing request with the 
Hearing Clerk as described in 40 CFR part 178, please submit a copy of 
the filing (excluding any Confidential Business Information (CBI)) for 
inclusion in the public docket. Information not marked confidential 
pursuant to 40 CFR part 2 may be disclosed publicly by EPA without 
prior notice. Submit the non-CBI copy of your objection or hearing 
request, identified by docket ID number EPA-HQ-OPP-2011-0852, by one of 
the following methods:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be CBI or other 
information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 
20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at https://www.epa.gov/dockets/contacts.htm. Additional 
instructions on commenting or visiting the docket, along with more 
information about dockets generally, is available at https://www.epa.gov/dockets.

II. Background and Statutory Findings

    EPA, on its own initiative, in accordance with FFDCA sections 
408(e) and 408(l)(6) of, 21 U.S.C. 346a(e) and 346a(1)(6), is 
establishing time-limited tolerances for residues of streptomycin, 5-
(2,4-diguanidino-3,5,6-trihydroxy-cyclohexoxy)-4-[4,5-dihydroxy-6-
(hydroxymethyl)-3-methylamino-tetrahydropyran-2-yl] oxy-3-hydroxy-2-
methyl-tetrahydrofuran-3-carbaldehyde, in or on grapefruit at 0.15 
parts per million (ppm) and dried grapefruit pulp at 0.40 ppm. 
Streptomycin is an antibiotic of the aminoglycoside class and is 
produced by the bacteria streptomyces. The active pesticide ingredient, 
streptomycin sulfate, dissociates in water to streptomycin, but 
otherwise is relatively stable in crops, animals, and humans. 
Therefore, compliance with the tolerance levels is determined by 
measuring the residues of streptomycin only and there are no 
toxicologically significant metabolites and/or degradates. Streptomycin 
and streptomycin sulfate are considered equivalent in this document and 
both are referred to as streptomycin. These time-limited tolerances 
expire on December 31, 2015.
    Section 408(l)(6) of FFDCA requires EPA to establish a time-limited 
tolerance or exemption from the requirement for a tolerance for 
pesticide chemical residues in food that will result from the use of a 
pesticide under an emergency exemption granted by EPA under FIFRA 
section 18. Such tolerances can be established without providing notice 
or period for public comment. EPA does not intend for its actions on 
FIFRA section 18 related time-limited tolerances to set binding 
precedents for the application of FFDCA section 408 and the safety 
standard to other tolerances and exemptions. Section 408(e) of FFDCA 
allows EPA to establish a tolerance or an exemption from the 
requirement of a tolerance on its own initiative, i.e., without having 
received any petition from an outside party.
    Section 408(b)(2)(A)(i) of 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 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. . . 
.''
    Section 18 of FIFRA authorizes EPA to exempt any Federal or State 
agency from any provision of FIFRA, if EPA determines that ``emergency 
conditions exist which require such exemption.'' EPA has established 
regulations governing such emergency exemptions in 40 CFR part 166.

III. Emergency Exemption for Streptomycin on Grapefruit and FFDCA 
Tolerances

    The Florida Department of Agriculture and Consumer Services (FDACS) 
requested an emergency exemption for use of streptomycin on up to 
54,000 acres of fresh-market grapefruit to combat citrus canker, a 
disease caused by the bacteria Xanthomonas citri. Citrus canker was 
once limited to localized areas in Florida, but several recent severe 
hurricane seasons have spread the disease throughout the citrus growing 
areas and widespread treatment to control the disease throughout the 
season has become necessary. The FDACS requested a maximum of 2 
applications of streptomycin, by ground equipment only, at a rate of 
0.448 pounds of active ingredient per acre per application, during the 
hottest part of the season when the risk of fruit injury from the 
alternative controls is the greatest. After having reviewed the 
submission, EPA determined that an emergency condition exists for this 
State, and that the criteria for approval

[[Page 29051]]

of an emergency exemption are met. EPA has authorized a specific 
exemption under FIFRA section 18 for the use of streptomycin on 
grapefruit for control of citrus canker in Florida.
    As part of its evaluation of the emergency exemption application, 
EPA assessed the potential risks presented by residues of streptomycin 
in or on grapefruit. In doing so, EPA considered the safety standard in 
FFDCA section 408(b)(2), and EPA decided that the necessary tolerance 
under FFDCA section 408(l)(6) would be consistent with the safety 
standard and with FIFRA section 18. Consistent with the need to move 
quickly on the emergency exemption in order to address an urgent non-
routine situation and to ensure that the resulting food is safe and 
lawful, EPA is issuing this tolerance without notice and opportunity 
for public comment as provided in FFDCA section 408(l)(6). Although 
these time-limited tolerances expire on December 31, 2015, under FFDCA 
section 408(l)(5), residues of the pesticide not in excess of the 
amounts specified in the tolerances remaining in or on grapefruit and 
grapefruit, dried pulp after that date will not be unlawful, provided 
the pesticide was applied in a manner that was lawful under FIFRA, and 
the residues do not exceed a level that was authorized by these time-
limited tolerances at the time of that application. EPA will take 
action to revoke these time-limited tolerances earlier if any 
experience with, scientific data on, or other relevant information on 
this pesticide indicate that the residues are not safe.
    Because these time-limited tolerances are being approved under 
emergency conditions, EPA has not made any decisions about whether 
streptomycin meets FIFRA's registration requirements for use on 
grapefruit or whether permanent tolerances for this use would be 
appropriate. Under these circumstances, EPA does not believe that this 
time-limited tolerance decision serves as a basis for registration of 
streptomycin by a State for special local needs under FIFRA section 
24(c). Nor does this tolerance by itself serve as the authority for 
persons in any State other than Florida to use this pesticide on the 
applicable crops under FIFRA section 18 absent the issuance of an 
emergency exemption applicable within that State. For additional 
information regarding the emergency exemption for streptomycin, contact 
the Agency's Registration Division at the address provided under FOR 
FURTHER INFORMATION CONTACT.

IV. Aggregate Risk Assessment and Determination of Safety

    Specific information on the studies reviewed and the nature of the 
adverse effects caused by streptomycin as well as the no-observed-
adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-
level (LOAEL) from the toxicity studies can be found at https://www.regulations.gov, under docket ID number EPA-HQ-OPP-2011-0852, in 
the document titled ``Streptomycin sulfate. Section 18 Petition by the 
Florida Department of Agriculture and Consumer Services for use on 
Grapefruit.''
    Consistent with the factors specified in FFDCA section 
408(b)(2)(D), 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, the aggregate 
exposures expected as a result of this emergency exemption request and 
the time-limited tolerances for residues of streptomycin in or on 
grapefruit at 0.15 ppm, and grapefruit, dried pulp at 0.40 ppm. EPA's 
assessment of exposures and risks associated with establishing the 
time-limited tolerances follows.

A. 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 non-threshold risk in terms of the probability of an 
occurrence of the adverse effect during a lifetime. For more 
information on the general principles EPA uses in risk characterization 
and a complete description of the risk assessment process, see https://www.epa.gov/pesticides/factsheets/riskassess.htm.
    A summary of the toxicological endpoints for streptomycin used for 
human risk assessment is shown in the Table of this unit.

      Summary of Toxicological Doses and Endpoints for Streptomycin for Use in Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                        Point of departure and
          Exposure/scenario               uncertainty/safety     RfD, PAD, LOC for risk  Study and toxicological
                                               factors                 assessment                effects
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Acute dietary........................  NA.....................  NA.....................  Toxicity from single
(Any population).....................                                                     dose exposure not
                                                                                          identified.
Chronic dietary......................  NOAEL= 5 mg/kg/day.....  Chronic RfD = 0.05 mg/   Two-year feeding study
(All populations)....................  UFA = 10...............   kg/day.                  in rats.
                                       UFH = 10...............  cPAD = 0.05 mg/kg/day..  LOAEL = 10 mg/kg/day
                                       FQPA SF = 1X...........                            based on reduced body
                                                                                          weight gain.
Cancer...............................               NA--EPA Waived its toxicology data requirements
----------------------------------------------------------------------------------------------------------------
FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level
  of concern. mg/kg/day = milligram/kilogram/day. MOE = margin of exposure. NOAEL = no-observed-adverse-effect-
  level. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. UFA = extrapolation from
  animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population
  (intraspecies).

    The human risk assessment for this action can be found at https://www.regulations.gov in the document ``Streptomycin sulfate. Section 18 
Petition by the Florida Department of Agriculture and Consumer Services 
for Use on Grapefruit'' in the docket for ID number EPA-HQ-OPP-2011-
0852.

[[Page 29052]]

B. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to streptomycin, EPA considered exposure under the time-
limited tolerances established by this action as well as all existing 
streptomycin tolerances in 40 CFR 180.245. EPA assessed dietary 
exposures from streptomycin in food as follows:
    i. Acute exposure. No such acute adverse effects were identified in 
the toxicological studies for streptomycin; therefore, a quantitative 
acute dietary exposure assessment is unnecessary.
    ii. Chronic exposure. In conducting the chronic dietary exposure 
assessment, EPA used food consumption information from the U.S. 
Department of Agriculture (USDA) 1994-1996 and 1998 Nationwide 
Continuing Surveys of Food Intake by Individuals (CSFII). As to residue 
levels in food, EPA used tolerance level residues for all registered 
commodities, and the proposed tolerance levels of 0.15 ppm for 
grapefruit and grapefruit juice. In addition, default processing 
factors were used for all commodities except grapefruit juice. One 
hundred percent crop treated (PCT) was assumed for all crops.
    iii. Cancer. No concern for carcinogenicity is expected for 
streptomycin based on the weight of evidence of available information. 
Streptomycin has been used for decades as a human drug at doses much 
higher than those expected from pesticidal uses, without findings of an 
association with cancer. Based on this information combined with the 
lack of tumors reported in the 2-year rat study assessed by FDA, and 
the properties of the molecule (e.g., minimal metabolism and large 
molecular size restricting interaction of the chemical with typical 
carcinogenic receptors) EPA has waived its toxicological data 
requirements for streptomycin. EPA has concluded that streptomycin does 
not pose a cancer risk to humans and a quantitative data requirements 
for streptomycin dietary exposure assessment for assessing cancer risk 
was not conducted.
    iv. Anticipated residue and PCT information. EPA did not use 
anticipated residue and/or PCT information in the dietary assessment 
for streptomycin. Tolerance level residues and 100 PCT were assumed for 
all food commodities.
    2. Dietary exposure from drinking water. The Agency used screening 
level water exposure models in the dietary exposure analysis and risk 
assessment for streptomycin in drinking water. These simulation models 
take into account data on the physical, chemical, and fate/transport 
characteristics of streptomycin. Further information regarding EPA 
drinking water models used in pesticide exposure assessment can be 
found at https://www.epa.gov/oppefed1/models/water/index.htm.
    Based on the First Index Reservoir Screening Tool (FIRST), and 
Screening Concentration in Ground Water (SCI-GROW) models, for surface 
and ground water, respectively, the estimated drinking water 
concentrations (EDWCs) of streptomycin for ground and surface water 
were calculated as 1.2 parts per billion (ppb) and 51.4 ppb, 
respectively. The EDWCs are based on aerial application to apple 
orchards, which is the highest rate allowed by the label.
    Modeled estimates of drinking water concentrations were directly 
entered into the dietary exposure model. For chronic dietary risk 
assessment, the EDWC value of 51.4 ppb for surface water was used to 
assess the dietary exposure contribution from drinking water.
    3. From non-dietary exposure. The term ``residential exposure'' is 
used in this document to refer to non-occupational, non-dietary 
exposure (e.g., for lawn and garden pest control, indoor pest control, 
termiticides, and flea and tick control on pets).
    Streptomycin is currently registered for the following uses that 
could result in residential exposures: Use in residential areas on 
trees and shrubs to control the same diseases (e.g., blight, various 
rots) for which it is used in commercial greenhouse and agricultural 
settings.
    EPA assessed residential nondietary exposure using the following 
assumptions: Since streptomycin is not significantly absorbed through 
dermal route, only inhalation exposures were assessed for residential 
scenarios of homeowner application to fruit trees and shrubs using a 
low pressure handwand. Although a quantitative residential post-
application inhalation exposure assessment was not performed, an 
occupational inhalation exposure assessment for handlers was performed 
which is representative of a higher-end, more intensive inhalation 
exposure. Thus, this assessment is also protective for evaluating any 
potential residential post-application inhalation exposure. Further 
information regarding EPA standard assumptions and generic inputs for 
residential exposures may be found at: https://www.epa.gov/pesticides/trac/science/trac6a05.pdf.
    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 streptomycin to share a common mechanism of 
toxicity with any other substances, and streptomycin does not appear to 
produce a toxic metabolite produced by other substances. For the 
purposes of this tolerance action, therefore, EPA has assumed that 
streptomycin 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 https://www.epa.gov/pesticides/cumulative.

C. Safety Factor for Infants and Children

    1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA 
shall apply an additional tenfold (10X) margin of safety for infants 
and children in the case of threshold effects to account for prenatal 
and postnatal toxicity and the completeness of the database on toxicity 
and exposure unless EPA determines based on reliable data that a 
different margin of safety will be safe for infants and children. This 
additional margin of safety is commonly referred to as the Food Quality 
Protection Act (FQPA) Safety Factor (SF). In applying this provision, 
EPA either retains the default value of 10X, or uses a different 
additional SF when reliable data available to EPA support the choice of 
a different factor.
    2. Prenatal and postnatal sensitivity. In a rabbit developmental 
toxicity study, no teratogenic effects were observed at the highest 
dose tested (10 milligrams/kilogram/day (mg/kg/day) orally). However, 
women receiving clinical treatment at doses of approximately 15 mg/kg/
day by intramuscular injection of streptomycin during pregnancy have 
been known to give birth to children with hearing loss or vestibular 
problems; no other teratogenic effects have been attributed to 
streptomycin treatment. Because only about 1% of an oral dose of 
streptomycin is absorbed by the body, that intramuscular injection 
corresponds to approximately 1,500 mg/kg/day by the oral route. Thus 
the pharmacological dose at which these prenatal effects have been 
observed is about 150 times higher than the no observed adverse effect 
level in the rabbit developmental toxicity study, and

[[Page 29053]]

approximately 30,000 times higher than the dose that produced the 
reduced weight gain endpoint used in establishing the chronic RfD, EPA 
is confident that the RfD will protect against teratogenic effects.
    3. Conclusion. EPA has determined that reliable data show that the 
safety of infants and children would be adequately protected if the 
FQPA SF were reduced to 1. That decision is based on the following 
findings:
    i. An extensive database exists from drug use of streptomycin in 
humans and animals, and all guideline toxicity data requirements for 
streptomycin have been waived. The toxicity of streptomycin was 
assessed using toxicity reviews provided by the FDA and from the 
published literature on drug use. Because the dose selected for risk 
assessment from agricultural use (based upon anticipated maximum 
exposures) is based upon a toxicity endpoint (decreased weight gain in 
test animals) that occurs at a much lower oral dose than the injected 
dose at which prenatal effects occur in humans, there are no residual 
concerns and the FQPA safety factor was reduced to 1x.
    ii. There is some indication that streptomycin may be neurotoxic at 
the very high doses when injected as a drug. Injury to the 8th cranial 
nerve has been noted in some patients receiving streptomycin 
injections. However, this injury occurs because streptomycin 
accumulates in the inner ear and is not indicative of systemic injury 
to the nervous system. Other rare conditions reported in patients 
treated with streptomycin injections at clinical doses include 
neuromuscular blockade associated with anesthesia, enlarged blind spots 
of the eye, and paresthesia or abnormal sensations. Again, these 
responses are rare and occurred with large pharmacological doses at 
approximately 30,000 times higher than the RfD for streptomycin. A 
developmental neurotoxicity study is therefore not recommended, and 
there is no need for additional UFs to account for neurotoxicity.
    iii. There was no evidence that in utero rabbits have increased 
susceptibility to streptomycin in the prenatal developmental study. A 
reproductive toxicity study has been waived and is therefore not 
available. Some children of mothers treated during pregnancy with 
streptomycin have been born with hearing deficits, which may indicate 
that the developing fetus is more sensitive than the mother to 
streptomycin-induced inner ear toxicity. However, these effects 
occurred after treatment with a directly injected pharmacological dose 
which is comparable to a dose about 150 times higher than the no 
observed adverse effect level in the rabbit developmental toxicity 
study, and approximately 30,000 times the chronic RfD EPA has selected 
for risk management purposes. At the much lower dose that EPA is using 
for risk management, there are no residual concerns. Therefore there 
are no concerns for prenatal effects.
    iv. There are no residual uncertainties identified in the exposure 
databases; all guideline toxicity data requirements were waived because 
of the extensive clinical information available for streptomycin from 
decades of use as a drug in humans and animals. The dietary food 
exposure assessments were performed based on 100 PCT and tolerance-
level residues. EPA made conservative (protective) assumptions in the 
ground and surface water modeling used to assess exposure to 
streptomycin in drinking water. EPA used similarly conservative 
assumptions to assess post-application exposure of children as well as 
incidental oral exposure of toddlers. These assessments will not 
underestimate the exposure and risks posed by streptomycin.

D. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic dietary pesticide 
exposures are safe by comparing aggregate exposure estimates to the 
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA 
calculates the lifetime probability of experiencing 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 adverse effect endpoint was 
identified. Therefore, streptomycin 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 dietary 
exposure to streptomycin from food and water will utilize 13% of the 
cPAD for children 1-2 years old, the population group receiving the 
greatest exposure. Based on the explanation in the unit regarding 
residential use patterns, chronic residential exposure to residues of 
streptomycin 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). Streptomycin 
is currently registered for uses that could result in short-term 
residential exposure. However, no such effects were identified in the 
studies for streptomycin. The Agency has determined that the chronic 
risk assessment is adequately protective for short-term exposures, and 
it is appropriate to aggregate chronic exposure through food and water 
(considered background exposure) with short-term residential exposures 
to streptomycin. Using the exposure assumptions described in this unit 
for short-term exposures, EPA has concluded the combined short-term 
food, water, and residential exposures from the highest exposure 
scenario result in an aggregate MOE of 2,100. Because EPA's level of 
concern for streptomycin is an MOE of 100 or below, this MOE is not of 
concern. Although a quantitative residential post-application 
inhalation exposure assessment was not performed, the occupational 
inhalation exposure assessment performed for handlers is representative 
of a worse case inhalation exposure and therefore protective of any 
potential post-application inhalation exposure in residential 
scenarios. The lowest MOE from the occupational assessments was 560, 
and assumed no use of protective equipment such as a respirator. Since 
this is higher than EPA's level of concern of an MOE of 100 or below it 
is not of concern.
    4. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account intermediate-term non-dietary, non-occupational 
exposure plus chronic exposure to food and water (considered to be a 
background exposure level). Streptomycin is not registered for any use 
patterns that would result in intermediate-term residential exposure 
and no intermediate-term adverse effects have been identified. Because 
there is no intermediate-term residential exposure or adverse effects 
identified, 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 streptomycin.
    5. Aggregate cancer risk for U.S. population. A quantitative cancer

[[Page 29054]]

assessment is unnecessary. Available data suggest there are no concerns 
for cancer from exposure to streptomycin, and EPA has concluded that 
streptomycin is not expected to pose a cancer risk to humans.
    6. Antibiotic resistance risk. EPA estimated the potential for 
development of antibiotic resistance in pathogenic bacteria, in 
consideration of factors recommended by public health experts to 
sustain the effectiveness of antibiotic materials. EPA conducted a 
qualitative analysis of this use as outlined in FDA's Guidance for 
Industry (GFI) 152. FDA's GFI 152 addresses expansion 
of antibiotic uses outside clinical settings with respect to potential 
impact on resistance development. Existing resistance to streptomycin 
has diminished its use in clinical settings, although it is still used 
as a second line treatment for tuberculosis and used for several other 
bacterial diseases. However, based upon the limitations of the use 
under an emergency exemption, both in terms of rate and geographic 
area, EPA concluded that the use is expected to result in low risks of 
release into the environment, and subsequently low exposures. Thus, EPA 
determined that the overall rating for risks of resistance development 
from this emergency exemption use under an emergency exemption is 
``low.'' The analysis, ``Review of Florida Department of Agriculture/
AgroSource's Analysis of Streptomycin's Safety with Regard to Its 
Microbiological Effect on Bacteria of Human Health Concern (FDA/CVM 
Guidance to Industry 152)'', as well as FDA's GFI 
152, may be found at https://www.regulations.gov, under docket 
ID number EPA-HQ-OPP-2011-0852.
    7. Pharmaceutical aggregate risk. Section 408 of the FFDCA requires 
EPA to consider potential sources of exposure to a pesticide and 
related substances in addition to the dietary sources expected to 
result from a pesticide use subject to the tolerance. In order to 
determine whether to maintain a pesticide tolerance, EPA must 
``determine that there is a reasonable certainty of no harm.'' Under 
FFDCA section 505, the Food and Drug Administration reviews human drugs 
for safety and effectiveness and may approve a drug notwithstanding the 
possibility that some users may experience adverse side effects. EPA 
does not believe that, for purposes of the section 408 dietary risk 
assessment, it is compelled to treat a pharmaceutical user the same as 
a non-user, or to assume that combined exposures to pesticide and 
pharmaceutical residues that lead to a physiological effect in the user 
constitutes ``harm'' under the meaning of section 408 of the FFDCA.
    Rather, EPA believes the appropriate way to consider the 
pharmaceutical use of streptomycin in its risk assessment is to examine 
the impact that the additional nonoccupational pesticide exposures 
would have to a pharmaceutical user exposed to a related (or, in some 
cases, the same) compound. Where the additional pesticide exposure has 
no more than a minimal impact on the pharmaceutical user, EPA could 
make a reasonable certainty of no harm finding for the pesticide 
tolerances of that compound under section 408 of the FFDCA. If the 
potential impact on the pharmaceutical user as a result of co-exposure 
from pesticide use is more than minimal, then EPA would not be able to 
conclude that dietary residues were safe, and would need to discuss 
with FDA appropriate measures to reduce exposure from one or both 
sources.
    Injected drug doses are approximately 15 mg/kg/day. Because the 
oral absorption of streptomycin is <1%, this corresponds to an oral 
equivalent dose of 1,500 mg/kg/day. This oral equivalent dose is 
approximately 375,000 times the highest dietary exposure estimate of 
0.004 mg/kg/day (the food and water exposure estimate for the highest-
exposed population (children 1-2 years old)). Therefore, dietary 
exposure from pesticide uses of streptomycin is negligible compared to 
drug exposure and would not contribute to drug toxicity, so there are 
no concerns for risks from dietary contribution of streptomycin 
exposure from pesticide use, in patients receiving streptomycin drug 
injections. Because the pesticide exposure has no more than a minimal 
impact on the total dose to a pharmaceutical user, EPA believes that 
there is a reasonable certainty that no harm will result from the 
potential dietary pesticide exposure of a user being treated 
therapeutically with streptomycin.
    8. 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 streptomycin residues.

V. Other Considerations

A. Analytical Enforcement Methodology

    An adequate enforcement methodology, ``Confirmation of 
Aminoglycosides by HPCL-MS/MS''; United States Department of 
Agriculture, Food Safety and Inspection Service, Office of Public 
Health Science, SOP No: CLG-AMG1.02, using high performance liquid 
chromatography with tandem mass spectrometry for detection (HPLC-MS/
MS), is available to enforce the tolerance expression.
    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; email address: 
residuemethods@epa.gov.

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 United Nations 
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 an MRL for streptomycin on 
grapefruit.

VI. Conclusion

    Therefore, time-limited tolerances are established for residues of 
streptomycin, in or on grapefruit at 0.15 ppm and grapefruit, dried 
pulp at 0.40 ppm. These tolerances expire on December 31, 2015.

VII. Statutory and Executive Order Reviews

    This final rule establishes tolerances under FFDCA sections 408(e) 
and 408(l)(6). The Office of Management and Budget (OMB) has exempted 
these types of actions from review under Executive Order 12866, 
entitled ``Regulatory Planning and Review'' (58 FR 51735, October 4, 
1993). Because this final rule has been exempted from review under 
Executive Order 12866, this final rule is not subject to Executive 
Order 13211, entitled ``Actions Concerning Regulations That 
Significantly Affect Energy Supply, Distribution, or Use'' (66 FR 
28355, May 22, 2001) or Executive Order 13045, entitled ``Protection of 
Children from Environmental Health Risks and Safety Risks'' (62 FR 
19885, April 23, 1997). This final rule does not

[[Page 29055]]

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 in accordance 
with FFDCA sections 408(e) and 408(l)(6), such as the tolerances 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 FFDCA section 408(n)(4). As such, the Agency has determined that 
this action will not have a substantial direct effect on States or 
tribal governments, on the relationship between the national government 
and the States or tribal governments, or on the distribution of power 
and responsibilities among the various levels of government or between 
the Federal Government and Indian tribes. Thus, the Agency has 
determined that Executive Order 13132, entitled ``Federalism'' (64 FR 
43255, August 10, 1999) and Executive Order 13175, entitled 
``Consultation and Coordination with Indian Tribal Governments'' (65 FR 
67249, November 9, 2000) do not apply to this 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) (2 U.S.C. 1501 et seq.).
    This action does not involve any technical standards that would 
require Agency consideration of voluntary consensus standards pursuant 
to section 12(d) of the National Technology Transfer and Advancement 
Act of 1995 (NTTAA) (15 U.S.C. 272 note).

VIII. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.), 
EPA will submit a report containing this rule and other required 
information to the U.S. Senate, the U.S. House of Representatives, and 
the Comptroller General of the United States prior to publication of 
the rule in the Federal Register. This action is not a ``major rule'' 
as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

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

    Dated: May 9, 2013.
Daniel J. Rosenblatt,
Acting Director, Registration Division, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

    Authority:  21 U.S.C. 321(q), 346a and 371.


0
2. Section 180.245 is amended by adding paragraph (b) to read as 
follows:


Sec.  180.245  Streptomycin; tolerances for residues.

* * * * *
    (b) Section 18 emergency exemptions. Time-limited tolerances are 
established for residues of streptomycin, in or on the agricultural 
commodities, as specified in the following table, resulting from use of 
the pesticide pursuant to FIFRA section 18 emergency exemptions. 
Compliance with the tolerance levels listed in the following table is 
to be determined by measuring the levels of streptomycin only, in or on 
the commodities listed in the table. The tolerances expire on the dates 
specified in the table.

------------------------------------------------------------------------
                                                 Parts per    Expiration
                   Commodity                      million        date
------------------------------------------------------------------------
Grapefruit....................................         0.15   12/31/2015
Grapefruit, dried pulp........................         0.40   12/31/2015
------------------------------------------------------------------------

* * * * *
[FR Doc. 2013-11858 Filed 5-16-13; 8:45 am]
BILLING CODE 6560-50-P