[Federal Register Volume 64, Number 58 (Friday, March 26, 1999)]
[Rules and Regulations]
[Pages 14632-14639]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-7434]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300822; FRL-6069-7]
RIN 2070-AB78
Arsanilic acid [(4-aminophenyl) arsonic acid]; Time-Limited
Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes a time-limited tolerance for
residues of arsanilic acid [(4-aminophenyl) arsonic acid] in or on
grapefruit. Fleming Laboratories, Inc. requested this tolerance under
the Federal Food, Drug, and Cosmetic Act, as amended by the Food
Quality Protection Act of 1996. The tolerance will expire on February
28, 2001.
DATES: This regulation is effective March 26, 1999. Objections and
requests for hearings must be received by EPA on or before May 26,
1999.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number [OPP-300822], must be submitted to: Hearing Clerk
(1900), Environmental Protection Agency, Rm. M3708, 401 M St., SW.,
Washington, DC 20460. Fees accompanying objections and hearing requests
shall be labeled ``Tolerance Petition Fees'' and forwarded to: EPA
Headquarters Accounting Operations Branch, OPP (Tolerance Fees), P.O.
Box 360277M, Pittsburgh, PA 15251. A copy of any objections and hearing
requests filed with the Hearing Clerk identified by the docket control
number, [OPP-300822], must also be submitted to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), Office of Pesticide Programs, Environmental Protection Agency,
401 M St., SW., Washington, DC 20460. In person, bring a copy of
objections and hearing requests to Rm. 119, Crystal Mall 2 (CM #2),
1921 Jefferson Davis Hwy., Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: [email protected]. Copies of electronic objections and
hearing requests must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption. Copies of objections and
hearing requests will also be accepted on disks in WordPerfect 5.1/6.1
or
[[Page 14633]]
ASCII file format. All copies of electronic objections and hearing
requests must be identified by the docket control number [OPP-300822].
No Confidential Business Information (CBI) should be submitted through
e-mail. Copies of electronic objections and hearing requests on this
rule may be filed online at many Federal Depository Libraries.
FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, Product
Manager 22, Registration Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location, telephone number, and e-mail address: Rm.
249, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA, 703 305-7740,
[email protected].
SUPPLEMENTARY INFORMATION: In the Federal Register of July 28, 1998 (63
FR 40273) (FRL-5799-3), EPA issued a notice pursuant to section 408 of
the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a, as
amended by the Food Quality Protection Act of 1996 (FQPA) (Pub. L. 104-
170) announcing the filing of a pesticide petition (PP 4G4276) for
tolerance in connection with an Experimental Use Permit (EUP) for (4-
aminophenyl) arsonic acid by Fleming Laboratories, Inc., P.O. Box
34384, Charlotte, NC 28234. This notice included a summary of the
petition prepared by Fleming Laboratories, Inc., the registrant. There
were comments received from two citrus growers supporting the approval
of the EUP in order to further develop and test (4-aminophenyl) arsonic
acid. Both growers are directors of consulting companies.
The petition requested that 40 CFR part 180 be amended by
establishing a time-limited tolerance for residues of the plant growth
regulator used as a ripening enhancement agent arsanilic acid [(4-
aminophenyl) arsonic acid], in or on grapefruit at 0.5 part per million
(ppm). The temporary tolerance on grapefruit is requested for fruit
resulting from the experimental use of arsanilic acid to evaluate
enhancement of ripening. The chemical will be tested on 50 acres of
grapefruit in the state of Florida for a period of 2 years. This
tolerance will expire on February 28, 2001.
I. Background and Statutory Findings
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) 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)
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 and a complete description of
the risk assessment process, see the final rule on Bifenthrin Pesticide
Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).
II. Aggregate Risk Assessment and Determination of Safety
Consistent with 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 arsanilic
acid [(4-aminophenyl) arsonic acid] and to make a determination on
aggregate exposure, consistent with section 408(b)(2), for a time-
limited tolerance for residues of (4-aminophenyl) arsonic acid in/on
grapefruit at 2.0 ppm (not to exceed 0.7 ppm total arsenic). EPA's
assessment of the dietary 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 arsanilic acid are
discussed in this unit.
1. Acute oral toxicity study. Groups of Sprague-Dawley rats (5/sex)
were given a single oral administration of arsanilic acid at doses of
500 (females), 750, 1,000, 1,250, or 1,500 milligrams/kilogram (mg/kg)
(males). Clinical signs consisted of: piloerection, hypoactivity,
soiled coat, hunched appearance, labored breathing, diarrhea, ataxia,
subdued behavior, stained perigenital area, emaciation, and red nasal
discharge. Oral LD50 results were as follows:
LD50 = 1,411 mg/kg (males)
LD50 = 976 mg/kg (females)
LD50 = 1,461 mg/kg (combined)
2. Acute dermal toxicity study. Groups of New Zealand White rabbits
(5/sex/dose) were given a single dermal application of arsanilic acid
at doses of 500, 1,000, or 2,000 mg/kg (Limit-Dose). Clinical signs of
toxicity observed at all dose levels included: ataxia, diarrhea, dark
urine, decreased defecation, convulsions, tremors, hindlimb paralysis,
hyper salivation, vocalization, red eyes, piloerection, labored
breathing, weight loss, hunched posture, and low food consumption
primarily 2-8 days post-dosing. Dermal LD50 results were as
follows:
LD50 = 922 mg/kg (males)
LD50 = 909 mg/kg (females)
LD50 = 921 mg/kg (combined)
3. Acute inhalation toxicity study. Groups of Sprague-Dawley rats
(5/sex) were exposed to aerosol concentrations of arsanilic acid 99.5%
at a maximum attainable analytical concentration of 5.3 mg/L for four
hours. Rats exhibited respiratory depression, subdued appearance, and
piloerection during exposure. Inhalation LC50 results were
as follows:
LC50 > 5.3 mg/L (both sexes).
4. Primary eye irritation study. Arsanilic acid was instilled into
the conjuctival sac of male New Zealand White rabbits. The results of
this study indicate that arsanilic acid is a slight ocular irritant to
rabbit.
5. Primary dermal irritation study. New Zealand White rabbits (6
males) were exposed to arsanilic acid on the intact skin for 4 hours.
No erythema or edema was observed in any of the test animals. The
primary Irritation Index is 0.0. The results of this study indicate
that arsanilic acid is a non-irritant to the skin of rabbits.
6. Dermal sensitization study. The dermal sensitization potential
of arsanilic acid was evaluated in 20 male Hartley guinea pigs
receiving dermal applications of 0.5 mL of the test material at
concentrations of 25%, 10%, 5%, or 2% w/v on three consecutive days for
three weeks (Induction Phase), followed by a 25% w/v application to the
original and virgin skin site four weeks later (Challenge Phase). None
of the treated animals exhibited any irritation when challenged; the
average skin reaction score for the virgin site was 0.0. Under the
conditions of this
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study, arsanilic acid 99.5% was not shown to be a sensitizer in guinea
pigs.
7. Developmental toxicity battery --i. Rat study. Pregnant Crl:CD
rats (25/dose) were administered arsanilic acid via oral gavage at dose
levels of 0, 10, 30, or 60 mg/kg/day during gestation days 6-15. The
test material in the powder form was mixed with Mazola corn oil for
administration to the test animals. Maternal toxicity was observed at
the highest dose tested (60 mg/kg/day) in the form of soft stool,
decreased defecation, mucoid feces and/or mucoid diarrhea, alopecia on
the abdomen or thorax, and red material around the nose. At the 30 mg/
kg/day doses, alopecia on the hindlimbs and abdomen was seen at an
increased frequency when compared to controls. Mean body weights were
significantly decreased at 60 mg/kg/day on gestation days 8, 9, and 1-
14, with a loss in mean body weight gain seen during gestation days 6-
9. At 30 mg/kg/day, mean body weights were significantly decreased on
gestation days 7, 8, 12, 13, and 15; mean body weight gain was
significantly decreased during days 6-16. At 60 mg/kg/day, a
significant decrease in food consumption was noted throughout the
treatment period followed by a significant recovery during the post-
treatment period. In the 10 and 30 mg/kg/day dose groups, significant
decreases in food consumption were noted throughout the treatment
period when compared to controls. Arsanilic acid did not induce
developmental toxicity at any of the doses tested. Based on these
results, the following is concluded:
Maternal No observable adverse effect level (NOAEL) = 6 mg/kg/day
Maternal Lowest observable adverse effect level (LOAEL) = 30 mg/kg/
day (based on decreased body weight gain and food consumption, and
clinical signs)
Developmental NOAEL = 60 mg/kg/day Highest dose tested (HDT)
ii. Rabbit study. Arsanilic acid in carboxymethyl cellulose was
administered by gavage to 20 New Zealand White female rabbits/dose at
dose levels of 0, 1, 3, or 6 mg/kg/day from days 7 through 19 of
gestation. Maternal clinical toxicity included slightly increased
clinical signs (diarrhea, discolored feces, decreased defecation),
decreased bodyweight gains, and decreased food consumption in the high-
dose group. No treatment-related differences in clinical signs,
bodyweight gain, or food consumption were observed in the mid- and low-
dose groups. The numbers of corpora, total implantations, and viable
fetuses were decreased in a dose-dependent fashion compared to
concurrent controls, but were within historical control ranges. Pre-
implantation losses were increased in a dose-dependent fashion;
however, the standard deviations were large and historical control data
were not provided. The extent of resorptions, post-implantation losses,
and mean fetal weights were similar between control and treated groups.
Although the observed maternal toxicity was marginal, the dose levels
used in this developmental study were adequate. In a range finding
study in which rabbits were dosed with arsanilic acid at 5-80 mg/kg/day
from days 7-19 of gestation, all animals in the 20, 40 and 80 mg/kg/day
groups and three animals in the 10 mg/kg/day group died, were
euthanized, or aborted prior to the scheduled necropsy. Clinical signs,
and differences in bodyweight gains and food consumption were detected
in the 5 and 10 mg/kg/day groups. Based on these results, the following
is concluded:
Maternal NOAEL = 3 mg/kg/day
Maternal LOAEL = 6 mg/kg/day (Based on clinical signs, decreased
body weight gain, and decreased food consumption)
Developmental NOAEL 6 mg/kg/day (HDT)
8. Mutagenicity battery -- i. Ames study. In two independently
performed Salmonella typhimurium/mammalian microsome plate
incorporation assays, strains TA1535, TA1537, TA98, and TA100 were
exposed to 33, 100, 333, 1,000, 3,333, or 10,000 g/plate
arsanilic acid with or without S9 activation. The S9 fraction was
prepared from Arochlor 1254-induced rat livers and arsanilic acid was
delivered to the test system in dimethyl sulfoxide (DMSO). No
cytotoxicity or mutagenicity was observed in any strain at any dose
either in the presence or absence of S9 activation.
ii. Mouse lymphoma mutation study. There were two independently
performed mouse lymphoma forward mutation assays. Target cells exposed
to arsanilic acid at doses of 112, 225, 450, 900, or 1,800 g/
mL with or without S9 activation were evaluated in the initial assay.
Non-activated 600, 900, 1,200, 1,500, or 1,800 g/L or S9-
activated 800, 1050, 1,300, 1,550, or 1,800 g/mL were assessed
in the confirmatory test. S9 activation was derived from Arochlor 1254-
induced rat livers and the test material was delivered in DMSO.
Arsanilic acid was positive with S-9 activation at 1,800 g/mL
in both independent trials. Under non-activated conditions, a positive
response was observed only at high cytotoxicity (4% relative suspension
growth) in the initial assay, and the confirmatory assay was negative.
Although the mutation assay was repeated several times due to widely
varying cytotoxicity data, the results were consistent between the two
acceptable assays and could be at least partially explained by a steep
cytotoxicity curve. Findings with the positive controls confirmed the
sensitivity of the test system to detect mutagenesis. Colony sizing at
the high dose indicated that the predominant mutations induced were
large chromosome deletions.
iii. Micronucleus assay study. In a mouse micronucleus assay,
groups of five CD-1 mice/sex/dose received single oral gavage
administrations of 0, 100, 200, or 400 mg/kg/day arsanilic acid for
three consecutive days. Dosing solutions of the test material were
prepared in 0.5% carboxymethyl cellulose. Mortalities, other clinical
signs of toxicity (piloerection, hunched appearance, hypothermia, and
cyanosis), and target tissue cytotoxicity were observed in the high-
dose group. There was, however, no significant increase in the
micronucleated polychromatic erythrocytes in bone marrow cells
harvested 24 or 48 hours post-treatment with the high dose or 24 hours
post-administration of the mid or low doses.
9. General metabolism study. The study demonstrated that arsanilic
acid is rapidly absorbed, distributed, and excreted following oral
administration in pigs and roosters. In four pigs administered 1.9-3.1
mg/kg 14C-arsanilic acid, total 3- or 4-day recovery of the
radioactivity was 92.3-97% of the administered dose, with higher
recovery in the urine (47.7-65.8% of the administered dose) than in the
feces (18.2-42.2% of the administered dose). Data suggested that
biliary excretions was a minor elimination route; only 4.7% of the
administered dose was recovered in the bile of a pig 3 days after
administration of 14C-arsanilic acid, recovery of
radioactivity in the excreta (63.4% of administered dose in urine,
26.6% in feces) was similar to that of the pigs; however, biliary
excretion was not determined. Tissue distribution and bioaccumulation
of arsanilic acid is low in pigs and roosters as indicated by low
recoveries of radioactivity in tissues 3 or 4 days after oral
administration. The metabolism of arsanilic acid does not appear to be
extensive. Unmetabolized parent compound and the metabolite, N-
acetylarsanilic acid, represented the highest amount of urinary
radioactivity in pigs; therefore, the major biotransformation reaction
of arsanilic acid in pigs appeared to be N-acetylation. Unmetabolized
arsanilic acid was the only radioactive
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component identified from the urine of roosters. Radioactivity in the
feces was not characterized for pigs or roosters.
10. Subchronic battery (90-day dog) study. Arsanilic acid was
administered to four beagle dogs/sex/dose group at dietary
concentrations of 0, 50, 100 or 200 ppm (equivalent to 0, 1.5, 3.2 or
6.9 mg/kg/day in males and 0, 1.7, 3.1 or 6.8 mg/kg/day in females) for
13 weeks. Because a NOAEL was not established in males of this initial
phase, an add-on phase was conducted in which arsanilic acid was
administered to four males/dose group at dietary concentrations of 0,
10 or 25 ppm (equivalent to 0, 0.3 or 0.7 mg/kg/day). In the initial
phase, the kidney was the target organ, based on microscopic kidney
alterations in all treated males and all 200 and 100 ppm group females.
The incidence and severity of kidney alterations increased with dose.
All treated male groups and both 100 and 200 ppm female groups had at
least one animal whose kidneys displayed tubule regeneration, tubule
dilatation, chronic inflammation, interstitial fibrosis, and papillary
necrosis. Kidneys of all 200 ppm group dogs had a granular/pitted/rough
appearance, irregular shape, dilated pelvis, pale material, pale area,
and/or enlarged size. The severity of the kidney alterations ranged
from slight in the 50 ppm group males to almost severe in the 200 ppm
group males and females. Renal function was impaired in the 200 ppm
male and female treatment groups, based on increased urea nitrogen at
Weeks 4, (138-207%), 8 (78-92%), and 13 (78-128%) compared to the
control values, and increased creatinine levels (1.0-1.3 mg/dL)
compared to the control and the 50 and 100 ppm group dogs (0.7-0.9 mg/
dL) at Weeks 4, 8, and 13. Though not statistically significant, all
treated male groups had absolute and relative (to body weight) kidney
weights around 20% higher than those of the control group. On the other
hand, the 200 ppm group males and females were anemic, based on 11-16%
decreased mean erythrocyte counts, hemoglobin, and hematocrit relative
to the control values at Weeks 8 and 13; the decreases were significant
(p 0.05) except for erythrocyte counts in males and
hemoglobin in females. No treatment-related effects were seen in the 50
ppm group females. In the add-on phase, the 25 and 10 ppm group males
were not adversely affected by treatment and there were no treatment-
related differences in hematology or clinical chemistry. In both
phases, no animals died and there were no treatment-related differences
in appearance, behavior, body weights, body weight gains, food
consumption, ophthalmology, and absolute or relative remaining organ
weights. Based on these results, the following is concluded:
NOAEL = 0.7 mg/kg/day (males)
NOAEL = 1.7 mg/kg/day (females)
LOAEL = 1.5 mg/kg/day (males - based on microscopic kidney
alterations)
LOAEL = 3.1 mg/kg/day (females - based microscopic kidney
alterations)
B. Toxicological Endpoints
1. Acute toxicity. For acute dietary exposure, a maternal NOAEL of
6 mg/kg/day was selected from a developmental toxicity study in rats.
The observed effects at the LOAEL of 30 mg/kg/day were decreased body
weight gain and food consumption and clinical signs. Using an
uncertainty factor of 100, the acute dietary reference dose (Acute
(RfD)) is 0.06 mg/kg/day. The additional 10x FQPA safety factor for
infants and children was removed.
2. Short - and intermediate-term toxicity. For non-dietary short-
term dermal exposure, an endpoint of 6 mg/kg/day was selected. This
endpoint was selected based on the developmental toxicity study in rats
and it was assumed that dermal absorption was 5%. For non-dietary
intermediate-term dermal exposure, an endpoint of 0.7 mg/kg/day was
selected. The result was selected based on the 13-week feeding study in
dogs and it was assumed that dermal absorption was 5%.
3. Chronic toxicity. EPA has established the RfD for arsanilic acid
at 0.0007 mg/kg/day. This RfD is based on 13-week dog study that had
NOAELs of 0.7 mg/kg/day for males and 1.7 mg/kg/day for females and an
uncertainty factor of 1000. The uncertainty factor was calculated based
on extrapolation from a subchronic dog study to a chronic scenario. The
LOAEL (1.5 mg/kg/day (males)/3.1 mg/kg/day (females)) caused
microscopic kidney alterations.
4. Carcinogenicity. There is no endpoint. This chemical has not
been classified yet.
C. Exposures and Risks
1. From food and feed uses. Currently, there are no tolerances
established for residues of arsanilic acid in or on any raw
agricultural commodities. Risk assessments were conducted by EPA to
assess dietary exposures from arsanilic acid as follows:
i. Acute dietary (food only) exposure and risk (Acute RfD = 0.06
mg/kg/day). Acute dietary risk assessments are performed for a food-
use pesticide if a toxicological study has indicated the possibility of
an effect of concern occurring as a result of a 1-day or single
exposure.
A Tier 1 acute Dietary Exposure Evaluation Model (DEEM) analysis
was performed reflecting the Theoretical Maximum Residue Concentration
(TMRC). The DEEM detailed acute analysis estimates of the distribution
of single-day exposures for the overall United States (U.S.) population
and certain subgroups. The analysis evaluates individual food
consumption as reported by respondents in the USDA 1989-91 Continuing
Survey of Food Intake by Individuals (CSFII) and accumulates exposure
to the chemical for each commodity. Each analysis assumes uniform
distribution of arsanilic acid in the commodity supply.
The acute exposure estimates at the 99.9 percentile and their
associated percentage of the acute reference dose (% Acute RfD) for the
general U.S. population and those populations within subgroups with the
highest exposure were calculated. None of the subgroups exceed 100% of
the acute RfD. The exposure estimates were as follows (from highest to
lowest): U.S. population (Spring) at 4% with 0.0026 mg/kg/day, children
(1-6 years) at 4% with 0.0021 mg/kg/day, males (20+ years) at 4% with
0.0021 mg/kg/day, U.S. population (48 states) at 3% with 0.0019 mg/kg/
day, females (13+ years, nursing) at 3% with 0.0020 mg/kg/day and
infants with no exposure. Therefore, the risk from acute dietary
exposure (food only) does not exceed the level of concern.
ii. Chronic dietary (food only) exposure and risk (chronic RfD =
0.0007 mg/kg/day). The chronic exposure estimates and their associated
percentage of the chronic reference dose (% Chronic RfD) for the
general U.S. population and those populations within subgroups with the
highest exposure were calculated. None of the subgroups exceed 100% of
the Chronic RfD. The exposure estimates were as follows (from highest
to lowest): U.S. Population (Winter) at 5% with 0.000033 mg/kg/day,
seniors (55+ years) at 5% with 0.000035 mg/kg/day, U.S. population (48
states) at 3% with 0.000018 mg/kg/day, females (20+ years, not
pregnant, not nursing) at 3% with 0.000024 mg/kg/day, children (7-12
years) at 2% with 0.000012 mg/kg/day, and infants with no exposure.
Therefore, the risk from chronic dietary exposure (food only) does not
exceed the level of concern.
2. From drinking water. Tentative summary data show that arsanilic
acid is persistent in soil and water, as evidenced by 1) its stability
in water, 2) spectroscopic inference of stability
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against photolytic breakdown in water and soil, and 3) aerobic and
anaerobic soil ``half-lives'' roughly estimated to be about 600 and 900
days, respectively. All degradates were accounted for, but not
identified, as they are, individually, less than 2% of the applied
radioactivity. However, as arsanilic acid slowly and inevitably
degrades, various arsenic containing moieties may enter the complex,
natural, arsenic biogeochemical cycle. In general, chemicals in the
cycle include highly toxic inorganic arsenicals and moderately toxic
organic arsenicals. These associated chemicals are slowly produced in
relatively low concentrations and, except for repeated annual
applications, would eventually be converted to near background levels
of locally dominant arsenic containing species in the various
environmental compartments (soil, water, air).
Although arsanilic acid is highly water soluble (approximately
5,000 ppm), this property is attenuated in the environment by the
compound's intermediate sorption to, or reaction with, soil mineral
and/or organic constituents (apparent or effective Koc
values ranging from approximately 4,000 to 11,000 mL/g; desorption
coefficients are significantly higher). With the combination of
persistence and intermediate mobility, arsanilic acid has potential for
runoff into surface water, with comparable amounts partitioned to
runoff water and eroding soil. For exposure to nontarget organisms,
surface water screening level concentrations based on GENEEC model are
22 and 37 ppb for acute (instantaneous) effects and 8.3 and 14 ppb for
chronic (56-day value) effects for use on pink/red and white grapefruit
varieties, respectively.
In most areas of the U.S., leaching of arsanilic acid to
groundwater is not expected to be significant. However, in the proposed
growing areas of Florida, groundwater contamination could be
problematic if application of this compound becomes widespread. Sandy
soils, shallow depth to groundwater, Karst strata and groundwater-
surface water interaction zones present a special situation for which
SCI-GROW, the current groundwater screening model, is not well-suited
and may be not be sufficiently conservative. The groundwater
concentration estimated from SCI-GROW is 0.080 ppb for pink/red and
0.13 ppb for white grapefruit varieties. USGS NAWQA monitoring data for
Dade County, Florida, reveal concentrations of total arsenic in shallow
groundwater over 1,000 times the maximum contaminant level (MCL) of 50
ppb, far above the SCI-GROW prediction. The extent and possible sources
and reasons for this contamination are under investigation at this
time. Arsenicals such as MSMA and cacodylic acid are among possible
sources.
The water solubility (polarity) of arsanilic acid would indicate
little tendency for bioconcentration. The reported sorption to soil,
which serves as a measure of potential bioconcentration for many
compounds, indicates that some bioconcentration may occur. With this
indication, and because of arsanilic acid's persistence and potential
for toxic concentrations in south Florida water bodies and sediment,
the Agency has recommended that additional bioconcentration studies
using oysters as the test organism be conducted. This study is needed
to show whether arsanilic acid is likely to concentrate in shellfish,
snails, etc., at levels which would pose dietary risks to aquatic
wildlife, including habituating birds and mammals.
3. From non-dietary exposure. Arsanilic acid is not registered for
use on residential non-food sites.
4. Cumulative exposure to substances with common mechanism of
toxicity. Section 408(b)(2)(D)(v) 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.'
Arsanilic acid is a member of the of the arsonic acid group of
arsenical herbicides (Ware, G.W. 1994. The Pesticide Book, 4th
edition). EPA does not have, at this time, available data to determine
whether the arsonic acid group has a common mechanism of toxicity with
other substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity, the
arsonic acid group 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 arsanilic acid 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 final rule for Bifenthrin Pesticide Tolerances (62 FR 62961,
November 26, 1997).
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk (food + water). The acute risk for ``food only'' does
not exceed the level of concern. The lowest acute drinking water level
of comparison (DWLOC) was for the infants/children subgroup at 580
g/L. The maximum surface water screening level concentration
for acute effects is 37 g/L. Therefore, acute exposure to
residues of arsanilic acid should not exceed the level of concern.
2. Chronic risk (food + water + residential). There are no current
registered residential uses. The chronic drinking water level of
comparison (DWLOC) for the U.S. population is 23 g/L. The
lowest DWLOC was for the infants/children subgroup at 7 g/L.
The highest surface water screening level concentration for chronic
effects is 14 g/L. However, the Agency believes that the
GENEEC model overstimates average residues in drinking water at least
3-fold. Therefore, chronic exposure to residues of arsanilic acid
should not exceed the level of concern.
3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account chronic dietary food and water
(considered to be a background exposure level) plus indoor and outdoor
residential exposure. Arsonic acid has no registered residential uses.
Therefore, short- and intermediate-term aggregate risk assessments were
not performed.
4. Aggregate cancer risk for U.S. population. Aggregate cancer risk
was not determined since cancer studies are not required for pesticides
to be tested under an Experimental Use Permit (EUP).
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
from aggregate exposure to residues of arsanilic acid.
E. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children-- i. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of arsanilic acid, EPA considered data from
developmental toxicity studies in the rat and rabbit and a 2-generation
reproduction study in the rat. The developmental toxicity studies are
designed to evaluate adverse effects on the developing organism
resulting from maternal pesticide exposure gestation. Reproduction
studies provide information relating to effects from exposure to the
pesticide on the reproductive capability of mating animals and data on
systemic toxicity.
[[Page 14637]]
FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of safety for infants and children in the case of
threshold effects to account for pre-and post-natal toxicity and the
completeness of the database 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 margin of exposure (MOE) analysis or through using
uncertainty (safety) factors in calculating a dose level that poses no
appreciable risk to humans. EPA believes that reliable data support
using the standard uncertainty factor (usually 100 for combined inter-
and intra-species variability) and not the additional tenfold MOE/
uncertainty factor when EPA has a complete data base under existing
guidelines and when the severity of the effect in infants or children
or the potency or unusual toxic properties of a compound do not raise
concerns regarding the adequacy of the standard MOE/safety factor.
ii. Conclusion. There is a complete toxicity database for an EUP
for arsanilic acid and exposure data is complete or is estimated based
on data that reasonably accounts for potential exposures. Therefore,
the additional 10x FQPA safety factor for infants and children was
removed.
2. Acute risk. The acute risk for ``food only'' does not exceed the
level of concern. The lowest acute DWLOC was for the infants/children
subgroup at 580 g/L. The maximum surface water screening level
concentration for acute effects is 37 g/L. Therefore, acute
exposure to residues of arsanilic acid should not exceed the level of
concern.
3. Chronic risk. Using the conservative exposure assumptions
described in this unit, EPA has concluded that aggregate exposure to
arsanilic acid from food will utilize 4% of the RfD for infants and
children. EPA generally has no concern for exposures below 100% of the
RfD because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health. Despite the potential for exposure to arsanilic
acid in drinking water (see discussion under U.S. population), EPA does
not expect the aggregate exposure to exceed 100% of the RfD. EPA
concludes that there is a reasonable certainty that no harm will result
to infants and children from aggregate exposure to arsanilic acid
residues.
4. Short- and intermediate risk. Short- and intermediate-term
aggregate exposure takes into account chronic dietary food and water
(considered to be a background exposure level) plus indoor and outdoor
residential exposure. Arsanilic acid has no registered residential
uses. Therefore, short- and intermediate-term aggregate risk
assessments were 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 infants and children from aggregate exposure to arsanilic acid
residues.
III. Other Considerations
A. Metabolism In Plants and Animals
An interim report from a study examining the metabolism and
distribution of arsanilic acid in grapefruit showed that arsanilic acid
and eleven metabolites were found in water extracts of the peel, pulp,
and juice fractions of the grapefruit. These compounds account for 83%
of the total radioactive residue (TRR) in/on grapefruit. The remaining
residues occur as organo-, acid-, or base-soluble components.
Identification of the metabolites is underway and one has been
tentatively identified as N-acetyl arsanilic acid. The majority of the
residues occur as arsanilic acid in/on the peel (26% TRR), as
Metabolite II in the pulp (3.8% TRR), and as Metabolite I in the juice
(7.3% TRR). On a whole-fruit basis, 29% of the TRR was unmetabolized
arsanilic acid with four metabolites of potential concern (
10% TRR) making up 51% of the TRR. The nature of the residues in plants
is not adequately understood. However, for purposes of this EUP only,
arsanilic acid per se will be considered the residue of concern.
As part of the proposed EUP labeling, grapefruit treated with
arsanilic acid will be restricted to fresh-market use only. Thus,
animal metabolism studies are not required for establishment of the
time-limited tolerances.
B. Analytical Enforcement Methodology
Adequate enforcement methodology is not available to enforce the
tolerance expression. A GC/ECD method is under development for the
determination of arsanilic acid in whole grapefruit. This method
currently demonstrates good extraction efficiency but suffers from poor
reproducibility during derivatization and chromatography. The limit of
quantitation for the method is expected to be 0.05 ppm arsanilic acid
in whole grapefruit. For purposes of tolerance enforcement for this
time-limited tolerance only, the Agency will accept a method for the
analysis of whole-fruit total arsenic by atomic absorption. The method
may be requested from: Calvin Furlow, PIRIB, IRSD (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location and telephone number: Rm 101FF,
CM #2, 1921 Jefferson Davis Hwy., Arlington, VA, (703) 305-5229.
C. Magnitude of Residues
Results of arsanilic acid field trial data are not yet available.
The registrant has proposed a whole-fruit tolerance of 0.5 ppm
arsanilic acid per se, based on data in the metabolic fate interim
study summary. Because this value was obtained from a non-replicated,
greenhouse study, the Agency believes that a tolerance of 0.5 ppm, as
proposed by the registrant, is not adequately supported. Previously-
submitted data indicate a tolerance of 2.0 ppm is appropriate. As a
result of this EUP, residues of arsanilic acid are not expected to
exceed 2 ppm in/on grapefruit. A time-limited tolerance should be
established at this level. This tolerance is equivalent to 0.7 ppm
arsenic, assuming arsanilic acid is the only source of arsenic. EPA is
finalizing this tolerance using a tolerance level at variance with that
requested in the petition based on consideration of all residue data
available, the relatively low risk presented by this tolerance, and the
limited exposure expected under the EUP connected with this tolerance.
Due to label restrictions, residues of arsanilic acid are not
expected in the juice, oil, or dried pulp of treated grapefruit as no
processed commodities are associated with this experimental use permit.
Secondary residues of arsanilic acid are not expected in animal
commodities as no feed items are associated with this experimental use
permit due to label restrictions.
D. International Residue Limits
There are no Codex, Canadian, or Mexican tolerances established for
arsanilic acid on grapefruit. Thus, international harmonization is not
an issue for these time-limited tolerances.
E. Rotational Crop Restrictions
Grapefruit are not rotated to other crops, therefore, residues in
or on rotational crops are not expected to occur.
IV. Conclusion
Therefore, the tolerance is established for residues of arsanilic
acid in /on grapefruit at 2.0 ppm (not to exceed 0.7 ppm total
arsenic).
[[Page 14638]]
V. Objections and Hearing Requests
The new FFDCA section 408(g) provides essentially the same process
for persons to ``object'' to a tolerance regulation as was provided in
the old section 408 and in section 409. However, the period for filing
objections is 60 days, rather than 30 days. EPA currently has
procedural regulations which govern the submission of objections and
hearing requests. These regulations will require some modification to
reflect the new law. However, until those modifications can be made,
EPA will continue to use those procedural regulations with appropriate
adjustments to reflect the new law.
Any person may, by May 26, 1999, file written objections to any
aspect of this regulation and may also request a hearing on those
objections. Objections and hearing requests must be filed with the
Hearing Clerk, at the address given under ``ADDRESSES'' section (40 CFR
178.20). A copy of the objections and/or hearing requests filed with
the Hearing Clerk should be submitted to the OPP docket for this
rulemaking. The objections submitted must specify the provisions of the
regulation deemed objectionable and the grounds for the objections (40
CFR 178.25). Each objection must be accompanied by the fee prescribed
by 40 CFR 180.33(i). EPA is authorized to waive any fee requirement
``when in the judgement of the Administrator such a waiver or refund is
equitable and not contrary to the purpose of this subsection.'' For
additional information regarding tolerance objection fee waivers,
contact James Tompkins, Registration Division (7505C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location, telephone number, and e-mail
address: Rm. 239, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA,
(703) 305-5697, [email protected]. Requests for waiver of tolerance
objection fees should be sent to James Hollins, Information Resources
and Services Division (7502C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
If a hearing is requested, the objections must include a statement
of the factual issues on which a hearing is requested, the requestor's
contentions on such issues, and a summary of any evidence relied upon
by the requestor (40 CFR 178.27). A request for a hearing will be
granted if the Administrator determines that the material submitted
shows the following: There is genuine and substantial issue of fact;
there is a reasonable possibility that available evidence identified by
the requestor would, if established, resolve one or more of such issues
in favor of the requestor, taking into account uncontested claims or
facts to the contrary; and resolution of the factual issues in the
manner sought by the requestor would be adequate to justify the action
requested (40 CFR 178.32). Information submitted in connection with an
objection or hearing request may be claimed confidential by marking any
part or all of that information as CBI. Information so marked will not
be disclosed except in accordance with procedures set forth in 40 CFR
part 2. A copy of the information that does not contain CBI must be
submitted for inclusion in the public record. Information not marked
confidential may be disclosed publicly by EPA without prior notice.
VI. Public Record and Electronic Submissions
EPA has established a record for this regulation under docket
control number [OPP-300822] (including any comments and data submitted
electronically). A public version of this record, including printed,
paper versions of electronic comments, which does not include any
information claimed as CBI, is available for inspection from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The public
record is located in Rm. 119 of the Public Information and Records
Integrity Branch, Information Resources and Services Division (7502C),
Office of Pesticide Programs, Environmental Protection Agency, CM 2,
1921 Jefferson Davis Hwy., Arlington, VA.
Objections and hearing requests may be sent by e-mail directly to
EPA at:
[email protected].
E-mailed objections and hearing requests must be submitted as an
ASCII file avoiding the use of special characters and any form of
encryption.
The official record for this regulation, as well as the public
version, as described in this unit will be kept in paper form.
Accordingly, EPA will transfer any copies of objections and hearing
requests received electronically into printed, paper form as they are
received and will place the paper copies in the official record which
will also include all comments submitted directly in writing. The
official record is the paper record maintained at the Virginia address
in ``ADDRESSES'' at the beginning of this document.
VII. Regulatory Assessment Requirements
A. Certain Acts and Executive Orders
This final 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). 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., or 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). Nor does
it require any or special considerations as required by Executive Order
12898, entitled Federal Actions to Address Environmental Justice in
Minority Populations and Low-Income Populations (59 FR 7629, February
16, 1994), or require OMB review in accordance with Executive Order
13045, entitled Protection of Children from Environmental Health Risks
and Safety Risks (62 FR 19885, April 23, 1997).
In addition, since tolerances and exemptions that are established
on the basis of a petition under FFDCA section 408(d), such as the
tolerance in this final rule, do not require the issuance of a proposed
rule, the requirements of the Regulatory Flexibility Act (RFA) (5
U.S.C. 601 et seq.) do not apply. Nevertheless, the Agency previously
assessed whether establishing tolerances, exemptions from tolerances,
raising tolerance levels or expanding exemptions might adversely impact
small entities and concluded, as a generic matter, that there is no
adverse economic impact. The factual basis for the Agency's generic
certification for tolerance actions published on May 4, 1981 (46 FR
24950), and was provided to the Chief Counsel for Advocacy of the Small
Business Administration.
B. Executive Order 12875
Under Executive Order 12875, entitled Enhancing the
Intergovernmental Partnership (58 FR 58093, October 28, 1993), EPA may
not issue a regulation that is not required by statute and that creates
a mandate upon a State, local or tribal government, unless the Federal
government provides the funds necessary to pay the direct compliance
costs incurred by those governments. If the mandate is unfunded, EPA
must provide to OMB a description of the extent of EPA's prior
[[Page 14639]]
consultation with representatives of affected State, local, and tribal
governments, the nature of their concerns, copies of any written
communications from the governments, and a statement supporting the
need to issue the regulation. In addition, Executive Order 12875
requires EPA to develop an effective process permitting elected
officials and other representatives of State, local, and tribal
governments ``to provide meaningful and timely input in the development
of regulatory proposals containing significant unfunded mandates.''
Today's rule does not create an unfunded Federal mandate on State,
local, or tribal governments. The rule does not impose any enforceable
duties on these entities. Accordingly, the requirements of section 1(a)
of Executive Order 12875 do not apply to this rule.
C. Executive Order 13084
Under Executive Order 13084, entitled Consultation and Coordination
with Indian Tribal Governments (63 FR 27655, May 19, 1998), EPA may not
issue a regulation that is not required by statute, that significantly
or uniquely affects the communities of Indian tribal governments, and
that imposes substantial direct compliance costs on those communities,
unless the Federal government provides the funds necessary to pay the
direct compliance costs incurred by the tribal governments. If the
mandate is unfunded, EPA must provide OMB, in a separately identified
section of the preamble to the rule, a description of the extent of
EPA's prior consultation with representatives of affected tribal
governments, a summary of the nature of their concerns, and a statement
supporting the need to issue the regulation. In addition, Executive
Order 13084 requires EPA to develop an effective process permitting
elected officials and other representatives of Indian tribal
governments ``to provide meaningful and timely input in the development
of regulatory policies on matters that significantly or uniquely affect
their communities.''
Today's rule does not significantly or uniquely affect the
communities of Indian tribal governments. This action does not involve
or impose any requirements that affect Indian tribes. Accordingly, the
requirements of section 3(b) of Executive Order 13084 do not apply to
this rule.
VIII. Submission to Congress and the Comptroller General
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the Agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and 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 the rule in the Federal Register. This 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: March 17, 1999.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is 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 180.550 is adding to read as follows:
Sec. 180.550 Arsanilic acid [(4-aminophenyl) arsonic acid]; tolerances
for residues.
(a) General. A time-limited tolerance is established for residues
of the plant growth regulator arsanilic acid [(4-aminophenyl) arsonic
acid], in or on the following food commodities in connection with the
use of the pesticide under section 5 experimental use permit. The
tolerance will expire on the date specified in the following table:
------------------------------------------------------------------------
Expiration/
Commodity Parts per million revocation date
------------------------------------------------------------------------
Grapefruit...................... 2 ppm (not to 2/28/01
exceed 0.7 ppm
total arsenic)
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 99-7434 Filed 3-25-99; 8:45 am]
BILLING CODE 6560-50-F