Document ID: EPA-HQ-OPP-2016-0416-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2016-08-12T04:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: [Richard Gebken, 703-305-6701]

 

INSTRUCTIONS:  Please utilize this outline in preparing the pesticide
petition.  In cases where the outline element does not apply, please
insert “NA-Remove” and maintain the outline. Please do not change
the margins, font, or format in your pesticide petition. Simply replace
the instructions that appear in green, i.e., “[insert company
name],” with the information specific to your action.

TEMPLATE:              

[BASF Corporation]

[Insert petition number]

	EPA has received a pesticide petition [Insert petition number] from
[BASF Corporation], [26 Davis Drive, P.O. Box 13528, Research Triangle
Park, North Carolina 27709-3528] proposing, pursuant to section 408(d)
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d),
to amend 40 CFR part 180 by establishing a tolerance for residues of the
insecticide [Afidopyropen, (BAS 440 I); [(3S,4R,4aR,6S, 6aS,
12R,12aS,12bS)-3-(cyclopropanecarbonyloxy)-6,12-dihydroxy-4,6a,12b-trime
thyl-11-oxo-9-(pyridin-3-yl)-1,2,3,4,4a,5,6,6a,12a,12b-decahydro-11H,12H
-benzo[ƒ]pyrano[4,3-b]chromen-4-yl]methyl cyclopropanecarboxylate, its
metabolites, and degradates] in or on the following raw agricultural
commodities: [almond hulls] at [0.15] parts per million (ppm) and
commodity [apple, wet pomace] at [0.05] parts per million (ppm), and
commodity [citrus oil] at [0.3] parts per million (ppm), and commodity
[cotton, gin byproducts] at [2] parts per million (ppm), and commodity
[cotton, undelinted seed] at [0.1] parts per million (ppm), and
commodity [fruit, citrus, group 10-10] at [0.15] parts per million
(ppm), and commodity [fruit, pome, group 11-10] at [0.03] parts per
million (ppm), and commodity [fruit, stone, group 12-12] at [0.03] parts
per million (ppm), and commodity [nut, tree, group 14-12] at [0.01]
parts per million (ppm), and commodity [plum, prune] at [0.06] parts per
million (ppm), and commodity [soybean, aspirated fractions] at [0.4]
parts per million (ppm), and commodity [soybean, forage] at [label
restriction] parts per million (ppm), and commodity [soybean, hay] at
[label restriction] parts per million (ppm) and commodity [soybean,
seed] at [0.01] parts per million (ppm), and commodity [vegetable,
brassica, head and stem group 5-13] at [0.5] parts per million (ppm),
and commodity [vegetable, cucurbit, group 9] at [0.7] parts per million
(ppm), and commodity [vegetable, fruiting, group 8-10] at [0.15] parts
per million (ppm), and commodity [vegetable, leaf petioles, subgroup
22B] at [3] parts per million (ppm), and commodity [vegetable, leafy,
subgroup 4-13A] at [2] parts per million (ppm), and commodity [vegetable
leafy, subgroup 4-13B] at [5] parts per million (ppm), and commodity
[vegetable tuberous and corm, subgroup 1C] at [0.01] parts per million
(ppm).  EPA has determined that the petition contains data or
information regarding the elements set forth in section 408 (d)(2) of
FDDCA; however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of the
petition. Additional data may be needed before EPA rules on the
petition.

A. Residue Chemistry

	1. Plant metabolism. [Nature of the residue studies were conducted in
cabbage, soybean and tomato as representative crops in order to
characterize the fate of Afidopyropen (BAS 440 I) in all crop matrices.
Two radiocarbon labels were studied in tomato and cabbage with 14C
labels positioned in nicotinic acid (nicotinic acid -9-14C) and pyranone
(pyranone-4-C14) part of the molecule. Soybean was investigated using
radiolabels in three different positions, nicotinic acid part of
molecule, pyranone -4-C14 and label in carbonyl of both
cyclopropanecarboxylic acid groups. BAS 440 I was the predominant
residue in most crops except soybean seed and the dimer metabolite
M440I007 was the only metabolite seen in significant levels in all
crops; trigonelline was a major component of soybean seed. In all crops
the BAS 440 I Residues of Concern (ROC) were characterized as parent BAS
440 I plus metabolite M440I007. Trigonelline, a product of niacin
metabolism, that occurs naturally in a wide range of plants,
particularly in legumes was determined as not a residue of concern after
discussion with US EPA and PMRA.  Confined rotational crop studies were
performed with the radiolabel in the nicotinic acid part of the
molecule, the pyranone part of the molecule and the carbonyl of the
cyclopropanecarboxylic acid groups. The confined rotational crop studies
demonstrated that no residues of concern were seen in the representative
rotational crops of wheat, radish, and spinach.]

	2. Analytical method. [An independently validated analytical method has
been submitted for analyzing residues of parent Afidopyropen (BAS 440 I)
plus metabolite M440I007 with appropriate sensitivity in all crop and
processed commodities. An independently validated analytical method has
been submitted for analyzing residues of parent Afidopyropen (BAS 440 I)
plus metabolite M440I001, M440I003 and M440I060 in animal meat, fat and
liver and egg and for BAS 440 I and metabolites M440I001, M440I005 and
M440I060 in milk with appropriate sensitivity in the event tolerances
are established. A multi-residue method using modified AOAC Official
method 2007.01 for the determination of residues of Afidopyropen (BAS
440 I) and metabolite M440I007 in plant matrices was successfully
validated.]

	3. Magnitude of residues. [Field trials were carried out to determine
the magnitude of the residue of Afidopyropen and metabolite M440I007
in/on cotton, undelinted seed; fruit, citrus; fruit, pome; fruit, stone;
nut, tree; soybean seed, soybean forage and hay; vegetable brassica,
head and stem; vegetable, cucurbit; vegetable, fruiting; vegetable, leaf
petiole, vegetable, leafy subgroups A and B and potato.  The number and
locations of field trials are in accordance with OPPTS Guideline
860.1500. Field trials were carried out using the maximum label rates,
the maximum number of applications, the minimum retreatment interval and
the minimum pre-harvest interval (PHI) for all the crops. Residues of
Afidopyropen were generally greater than the residues of M440I007 unless
both were <LOQ of 0.01 mg/kg. Detected residues of BAS 440 I in all
crops with residues measured at >LOQ support the proposed tolerances
based on parent Afidopyropen. No residues are anticipated in rotational
crops planted in accordance with the proposed labels. No residues are
anticipated in animal commodities due to the anticipated low animal
Maximum Reasonably Balanced Diets, and no tolerances in animal
commodities are proposed.]

B. Toxicological Profile

	1. Acute toxicity. [BAS 440 I has low acute toxicity by the oral,
percutaneous, and inhalation routes of administration. The test
substance is not irritating to the skin or the eye and is not a dermal
sensitizer. The acute toxicity studies place technical BAS 440 I in
toxicity category III for acute oral and dermal and category IV for
acute inhalation, eye and skin irritation. ]

 

	2. Genotoxicty. [Afidopyropen was tested for genotoxicity in a battery
of assays. Over a range of in vitro and in vivo studies, Afidopyropen
showed no indication of genotoxicity.]

	3. Reproductive and developmental toxicity. [BAS 440 I has a large
database studying the reproductive effects in the rat. Multiple studies
were conducted to fully characterize effects found at high doses. In the
definitive rat 2-generation reproduction study, the NOAEL for general,
systemic toxicity is 500 ppm (51 mg/kg bw/d) for the F0 and F1 parental
rats, based on decreased food consumption and body weight/body weight
gain observed at 2000 ppm (186 mg/kg bw/d) in all F0 and F1 parental
animals, as well as effects on hematology and clinical chemistry. The
NOAEL for fertility and reproductive performance for the parental rats
is 500 ppm (51 mg/kg bw/d) due to the reduction in implantation sites
and pups delivered in the F1 parents of the 2000 ppm (186 mg/kg bw/d)
dose group. The NOAEL for developmental toxicity in the F1 and F2
progeny is 100 ppm (11 mg/kg bw/d), due to the decrease in the
pre-weaning pup body weights/pup weight gains observed at the 500 ppm
(51 mg/kg bw/d) dose. This developmental effect was only observed during
the lactation portion of the study when the effective maternal dose was
doubled and the dose exhibited non-linear kinetics. Therefore in the
context of risk assessment this effect does not represent meaningful
evidence of increased pup sensitivity.

In the rabbit developmental study there were no adverse effects from BAS
440 I in maternal animals at any of the doses tested. Additionally,
there were no treatment-related adverse effects on fetuses at any of the
doses tested. Under the conditions of this study, both the maternal and
fetal NOAEL was determined to be 32 mg/kg bw/d.

In the definitive rat developmental toxicity study, the dose level of
200 mg/kg bw/d produced overt maternal toxicity, as evidenced by body
weight loss and one death. The dose level of 100 mg/kg bw/d also
produced a slight but statistically significant reduction in food
consumption during gestation days 6-9. For fetal parameters,
treatment-related effects were limited to a statistically significant
increase in the litter incidences of several skeletal variations in the
200 mg/kg bw/d group. These findings were only observed at a
maternally-toxic dose level that exceeds a kinetically derived maximum
tolerated dose The NOAEL for maternal toxicity in the rat is 50 mg/kg
bw. The NOAEL for developmental toxicity in the rat is 100 mg/kg bw/d.]

	4. Subchronic toxicity. [The short-term toxicity of BAS 440 I was
investigated in 28- and 90-day oral feeding studies in rats, mice and
dogs. Additionally, a 28-day repeated dose dermal exposure study in rats
was conducted.

The principal target organ in all studies was the liver, as indicated by
organ weight changes and associated histopathological changes at high
doses (lipid deposits). In the F344 rat, vacuolar changes (lipid
deposits) were also observed in the heart at high dose levels.
Additionally, at high doses in the F344 rat (no other species or strain
of rat), the uterus was a target, with consistently lower uterus weight.

 

Findings at the LOAEL were typically only mildly adverse (slight changes
in clinical chemistry, organ weight changes without severe
histopathological findings). At higher doses, particularly with the dog
and mice, treatment was not well tolerated, with severe effects on
clinical signs and mortality / moribundity.

 

Dermal administration of BAS 440 I to rats for 28-days did not result in
any treatment-related changes up to the limit dose of 1000 mg/kg.

The lowest NOAEL in subchronic oral toxicity studies was approximately
15 mg/kg bw/day in the dog 90-day study.

Acute and short-term (90 day) neurotoxicity studies were performed to
assess the neurotoxic potential of BAS 440 I. An acute neurotoxicity
study at a limit dose (2000 mg/kg bw) did not reveal any signs of
neurotoxicity. The NOAEL for acute neurotoxicity was established as 2000
mg/kg bw. There was no indication of clinical (general clinical
observation, FOB and motor activity) or neurohistopathological
neurotoxicity in a subchronic (90D) neurotoxicity study in the rat.
Systemic signs of toxicity, namely body weight reduction in the 90D
study, were consistent with effects observed in repeated dose studies
with BAS 440 I. The NOAEL for subchronic neurotoxicity was established
at the highest dose tested, 4000 ppm (238 mg/kg bw/d in males and 273
mg/kg bw in females)]

	5. Chronic toxicity. [Systemic toxicity in long term oral exposure
studies in dogs, mice and rats included effects on food consumption,
body weight development and clinical chemistry changes. The liver was
identified as the main target organ in all species tested, as indicated
by liver weight changes and non-neoplastic lesions. An additional target
organ at high doses in the F344 rat included the uterus. 

BAS 440 I was not carcinogenic to the CD1 mice at dose levels up to 4000
ppm (about 400 mg/kg bw/d).

Treatment of BAS 440 I for 2 years in F344/DuCrlCrlj rats resulted in
the induction of uterine adenocarcinomas in females at dose levels ≥
1000 ppm. Dose levels where these tumors were increased were found to be
above a kinetically derived maximum tolerated dose. At these high doses
mechanistic data indicates a dopamine enhancement mode of action that
leads to rat uterine adenocarcinomas. This mode of action for uterine
adenocarcinoma promotion is not relevant to humans due to both
qualitative and quantitative differences between rat and human. The
Afidopyropen data supports a non-genotoxic, non-human relevant,
threshold mode of action for formation of uterine adenocarcinomas in the
rat.

In a 1-year study with the dog, the NOAEL was found to be 8 mg/kg bw/d.
This endpoint represents the lowest endpoint for a long term exposure to
Afidopyropen.]

	6. Animal metabolism. [Rat, goat and hen metabolism studies were
conducted to determine the nature of the BAS 440 I residues in animals.
Studies were conducted with radiolabeled BAS 440 I with 14C labels
positioned in the nicotinic acid or pyranone part of the molecule for
the rat, in the pyranone ring or the carbonyl of both
cyclopropanecarboxylic acid groups for the goat, and in the carbonyl of
the cyclopropanecarboxylic acid groups for the hen. After administration
to animals, BAS 440 I was rapidly excreted, seen in low amounts in urine
but predominantly in feces, and was transformed to a number of
metabolites. The metabolism of BAS 440 I in the animals is generally
well understood. Degradation proceeds by cleavage of one or both of the
cyclopropanecarboxylic ester groups with release of M440I061, and
formation of M440I061 conjugates. In addition, oxidation of the pyridine
ring of parent occurs to form the N-oxide, M440I017. Unchanged parent,
M440I061 or M440I061-related metabolites such as M440I060 are found as
the predominant components in animal matrices. The same metabolic
reactions were observed in each of the animals studied, so there is a
consistent metabolic pathway for BAS 440 I in rat and livestock.

	7. Metabolite toxicology. [M440I007, a plant metabolite, was tested in
a battery of toxicology assays. M440I007 displays no genotoxic potential
and was not acutely toxic via the oral route. There were no treatment
related findings for any of the doses tested in the rat 90 day dietary
study up to the maximum dose tested, 10,000 ppm. The resulting NOAEL was
the highest dose tested (708 mg/kg bw in males and 797 mg/kg bw/d in
females).

M440I061 was established as a major metabolite in the rat. The rat is a
sensitive species to M440I061 toxicity. Therefore the NOAELs established
from a wide range of toxicology studies with Afidopyropen can be used to
establish protective endpoints for exposure to M440I061. Additionally, a
90D rat study tested M440I061 and established a NOAEL at 10 mg/kg bw/d.

	8. Endocrine disruption. [There were no significant findings in other
relevant toxicity studies (e.g., sub-chronic and chronic toxicity,
developmental toxicity and multi-generation reproductive studies) which
would suggest that BAS 440 I produces endocrine disruption.

In the transcriptional activation assay, BAS 440 I was not an agonist of
human estrogen receptor alpha (hERα) in the HeLa-9903 model system.

The weight of the evidence indicates BAS 440 I does not induce
human-relevant endocrine disruption.]

C. Aggregate Exposure 

	1. Dietary exposure. [The tolerance expression proposed for monitoring
and risk assessment in plant commodities is Afidopyropen, parent only. 
The parent is the significant residue in crops when residues are >LOQ.
Due to the significantly lower toxicity of the metabolite than toxicity
of parent, M440007 is not proposed for inclusion in the tolerance
expression for risk assessment. No tolerances are proposed in animal
commodities at this time. For potential future proposed tolerances in
animal commodities, the proposed tolerance expression for monitoring is
Afidopyropen and/or M440I060 depending on the matrix. The proposed
tolerance expression for dietary risk assessment in animal matrices is
Afidopyropen and M440I060.

Exposure assessments were conducted to evaluate the potential risk due
to acute and chronic dietary exposure of the U.S. population and all
sub-populations. The assessments were performed with DEEM-FCID version
4.02 with consumption data from the 2005-2010 NHANES surveys.]

	i. Food. [Acute Dietary Exposure Assessment 

The proposed endpoint for use in the acute dietary assessment is shown
in the following table.



Summary of toxicological dose and endpoint for Afidopyropen in acute
dietary assessment

Exposure/scenario	Point of departure	Uncertainty/ FQPA safety factor
RfD, PAD	Study and toxicological effects

Acute dietary (general population, including infants, children and
females 13-49 years of age	NOAEL = 32 mg/kg/d	UF = 10x

UF = 10x

FQPA SF = 1x	Acute RfD = 0.32 mg/kg/d

aPAD = 0.32 mg/kg/d	Rabbit developmental (developmental endpoint)

Inputs for acute dietary exposure estimates are proposed MRLs for all
crop commodities, 100 % crop treatment factor, and the processing
factors (PF) shown below.

Commodity	Process factor used in assessment

Fruit, citrus, group 10-10	Citrus peel: 1.6

Fruit, pome, group 11-10	Apple, dried: 8

Fruit, stone, group 12-12	Peach, dried: 6

Apricot, dried: 6

Vegetable fruiting, group 8-10	Tomato, dried: 5

Tomato puree:0.22

Tomato paste:0.5

Vegetable tuberous and corm, subgroup 1C	Dry  EPA default 5.5 

The residue levels for animal commodities (ruminant meat = 0.0006 mg/kg,
ruminant liver = 0.0005 mg/kg; milk = 0.0003 mg/kg; milk fat = 0.003
mg/kg) to use in the dietary assessment were derived from the cow
feeding study and goat metabolism study and adjusted based on the
anticipated Maximum Reasonably Balanced Diet.

For drinking water, all BAS 440 I uses were examined at maximum use
rates, maximum number of applications, and all proposed application
methods to determine which use would result in the highest water
concentrations. The highest peak water concentration of Afidopyropen
occurred from the cucumber use scenario. The highest acute Estimated
Environmental Concentration for Afidopyropen residue was estimated to be
2.70 µg/L (ppb) in surface water. The consumption of water, all direct
and indirect, was included in the dietary analysis, and the residue
concentration in water was set at 0.00270 mg/L based on the surface
water concentration determined for the proposed use in cucumber.

The resulting exposure estimates were compared against the Afidopyropen
acute Population Adjusted Dose (aPAD) of 0.32 mg/kg bw/day for all
populations. The most highly exposed sub-population was children 1-2
years old with 3.0% utilization of the aPAD. The results of the acute
dietary assessment are presented in Table 1.

Table 1. Results for BAS 440 I Acute Dietary Exposure (Food and Water)
Considering All Proposed Tolerances using DEEM-FCID at the 95th
Percentile

Population	Exposure Estimate	% aPAD

Subgroups	(mg/kg bw/day)

	General U.S. Population	0.005497	1.7

All Infants (< 1 year old)	0.006097	1.9

Children (1-2 years old)	0.009481	3.0

Children (3-5 years old)	0.008963	2.8

Children (6-12 years old)	0.006008	1.9

Youth (13-19 years old)	0.004142	1.3

Adults (20-49 years old)	0.005166	1.6

Adults (50+ years old)	0.005269	1.6

Females (13-49 years old)	0.005402	1.7

The results of the analysis show that for all populations, the estimated
exposures are well below the Agency's level of concern (< 100% aPAD).
Additional refinements in the dietary risk assessment (i.e. utilizing
anticipated residue values, percent crop treated values) would further
reduce the estimated exposure values.

Chronic Dietary Exposure Assessment 

The proposed endpoint for use in the chronic dietary assessment is shown
below.

Summary of toxicological dose and endpoint for Afidopyropen in chronic
dietary assessment

Exposure/scenario	Point of departure	Uncertainty/ FQPA safety factor
RfD, PAD	Study and toxicological effects

Chronic dietary  (all populations)	NOAEL = 8 mg/kg/d	UF = 10x

UF = 10x

FQPA SF = 1x	Chronic RfD = 0.08 mg/kg/d

cPAD = 0.08 mg/kg/d	One year dog  NOAEL = 8 mg/kg day based on
deposition of hyaline droplets in hepatocytes

Inputs for chronic dietary exposure estimates are proposed MRLs for all
crop commodities, 100 % crop treatment factor, the processing factors
(PF) and the residue levels in animal commodities used in the acute
assessment.

For drinking water all Afidopyropen uses were examined at maximum use
rates, maximum number of applications, and all proposed application
methods to determine which use would result in the highest water
concentrations. For drinking water, the 365 day average Estimated
Environmental Concentration for Afidopyropen residue occurring from the
cucumber use scenario was estimated to be 0.528 µg/L (ppb) in surface
water. The consumption of water, all direct and indirect, was included
in the dietary analysis, and the residue concentration in water was set
at 0.000528 mg/L based on the surface water average concentration
determined for the proposed use in cucumber.

The resulting exposure estimates were compared against the Afidopyropen
chronic Population Adjusted Dose (cPAD) of 0.08 mg/kg bw/day for all
populations. The results of the chronic dietary assessment including
food and water are presented in Table 2. The most highly exposed
population sub-group was children 1-2 years of age which utilized 3.4%
cPAD. 

Table 2.  Results for BAS 440 I Chronic Dietary Exposure (Food and
Water) Considering All Current, Pending, and Proposed Tolerances using
DEEM-FCID

Population	Exposure Estimate	% cPAD

Subgroups	(mg/kg bw/day)

	U.S. Population	0.001479	1.8

All Infants (< 1 year old)	0.001228	1.5

Children (1-2 years old)	0.002704	3.4

Children (3-5 years old)	0.002359	2.9

Children (6-12 years old)	0.00158	2.0

Youth (13-19 years old)	0.001083	1.4

Adults (20-49 years old)	0.00135	1.7

Adults (50+ years old)	0.001537	1.9

Females (13-49 years old)	0.001413	1.8

The results of the risk assessment show that for all populations the
exposures are below a level of concern (< 100% cPAD). Additional
refinements in the dietary risk assessment (i.e. utilizing anticipated
residue values, percent crop treated values) would further reduce the
estimated exposure values.]

	ii. Drinking water. [The consumption of Afidopyropen residues in
drinking water was included in the acute and chronic dietary assessments
above. 

M440I061 is a potential soil metabolite due to aerobic soil degradation
of Afidopyropen and thus has potential for residues in drinking water.
An endpoint for use in the dietary assessment of M440I061 in drinking
water is available from a 90 day study in rat performed with
Afidopyropen metabolite M440I061.



Summary of toxicological dose and endpoint for Afidopyropen metabolite
M440I061 in dietary assessment of M440I061 ingested as M440I061

Exposure/scenario	Point of departure	Uncertainty/ FQPA safety factor
RfD, PAD	Study and toxicological effects

Acute or chronic dietary  (all populations)	NOAEL = 10 mg/kg/d	UF = 10x

UF = 10x

FQPA SF = 1x	RfD = 0.10 mg/kg/d

aPAD = cPAD = 0.10 mg/kg/d	Repeat dose 90 day oral toxicity in rat

NOAEL = 10 mg/kg day

For drinking water all Afidopyropen uses were examined at maximum use
rates, maximum number of applications and all proposed application
methods to determine which use would result in the highest water
concentrations for the metabolite M440I061. The peak water concentration
of Afidopyropen metabolite M440I061 occurred from the tomato use
scenario; the peak Estimated Environmental Concentration for M440I061
residue was 2.810 µg/L (ppb) in surface water. For drinking water, the
365 day average Estimated Environmental Concentration for Afidopyropen
metabolite M440I061 residue occurring from the tomato use scenario was
estimated to be 0.986 µg/L (ppb) in surface water. The estimated
numbers were used in dietary assessments for direct and indirect
drinking water using DEEM-FCID, version 4.02.

The resulting acute or chronic exposure estimates for drinking water
were compared against the Afidopyropen metabolite M440I061 reference
dose of 0.10 mg/kg bw/day for all populations. The results for the acute
assessment and chronic assessment are presented in Tables 3 and 4,
respectively. The results show that the exposure to metabolite M440I061
in water is very low with the highest acute exposure for all infants
utilizing 0.51% of the reference dose and the highest chronic exposure
for all infants utilizing 0.04% of the reference dose. The exposure from
drinking water is very low and the contribution to the overall risk
assessment is not significant.  Therefore, the contribution from
M440I061 was not included in an aggregate risk assessment.

Table 3.  Results for Afidopyropen Metabolite M440I061 Acute Dietary
Exposure for Drinking Water Considering All Proposed Uses using
DEEM-FCID

Population	Exposure Estimate	% cPAD

Subgroups	(mg/kg bw/day)

	U.S. Population	0.00015	0.15

All Infants (< 1 year old)	0.000513	0.51

Children (1-2 years old)	0.000216	0.22

Children (3-5 years old)	0.00017	0.17

Children (6-12 years old)	0.000133	0.13

Youth (13-19 years old)	0.000125	0.13

Adults (20-49 years old)	0.000146	0.15

Adults (50+ years old)	0.000127	0.13

Females (13-49 years old)	0.000148	0.15

Table 4.  Results for Afidopyropen Metabolite M440I061 Chronic Dietary
Exposure for Drinking Water Considering All Proposed Uses using
DEEM-FCID

Population	Exposure Estimate	% cPAD

Subgroups	(mg/kg bw/day)

	U.S. Population	0.000011	0.01

All Infants (< 1 year old)	0.00004	0.04

Children (1-2 years old)	0.000015	0.015

Children (3-5 years old)	0.000012	0.01

Children (6-12 years old)	0.000009	0.01

Youth (13-19 years old)	0.000008	0.01

Adults (20-49 years old)	0.000011	0.01

Adults (50+ years old)	0.00001	0.01

Females (13-49 years old)	0.00001	0.01

	2. Non-dietary exposure. 

[BASF is proposing a greenhouse use on vegetable transplants that could
be sold to consumers. The dermal exposures for adults and children 6-11
years old calculated using EPA’s Residential SOPs indicate that the
potential exposure is very low for this use. Because no dermal hazard of
concern was identified for Afidopyropen, and no inhalation exposure is
expected for handling vegetable transplants, an aggregate exposure
determination is not required for this use.]

D. Cumulative Effects ["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." Unlike other pesticides for
which EPA has followed a cumulative risk approach based on a common
mechanism of toxicity, EPA has not made a common mechanism of toxicity
finding as to Afidopyropen. For the purposes of this tolerance action,
therefore, BASF has not assumed that Afidopyropen BAS 440 I has a common
mechanism of toxicity with other substances.]

E. Safety Determination

	1. U.S. population. [Based on this risk assessment, BASF concludes that
there is a reasonable certainty that no harm will result to the general
population from the aggregate exposure to Afidopyropen from the proposed
uses.]

	2. Infants and children. [Based on this risk assessment, BASF concludes
that there is a reasonable certainty that no harm will result to infants
or children from the aggregate exposure to Afidopyropen from the
proposed uses rotational crops.]

F. International Tolerances

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éÿ+

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(MRL) are established for residues of Afidopyropen.

There are no CODEX maximum residue levels established for residues of
Afidopyropen. ]

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