-------
D. Data Requirements
Data required in the June 1987 Registration Standard for paraquat dichloride
include studies on product chemistry, ecological effects, toxicology, environmental
fate, and residue chemistry. A Data Call-In issued December 1991 required further
testing for ecological effects, environmental fate and residue chemistry. These data
were required to support the uses listed in the Registration Standard. Appendix B
includes all data requirements identified by the Agency for currently registered uses
needed to support reregistration.
E. Regulatory History
Paraquat was discovered in 1882 and has been used as an oxidation-reduction
indicator under the name of methyl virologen since 1932. The first commercial
paraquat formulation for agricultural use was produced by Imperial Chemical
Industries, Ltd. in England and was registered there in 1962.
Paraquat dichloride was registered in the United States in 1964 for use as a
contact herbicide to control or suppress a broad spectrum of emerged weeds. The
Agency classified paraquat dichloride as a Restricted Use pesticide due to high acute
toxicity to animals and people from intentional or inadvertent exposure. This action
was taken by the Agency through regulations proposed in the September 1, 1977 (42
FR 44170) and finalized in the February 9,1978 (43 FR 5782) issues of the
FEDERAL REGISTER. Under the Restricted Use classification, only certified
applicators are authorized to apply paraquat dichloride end-use products.
In 1978 paraquat dichloride was accepted as a candidate for the Special Review
process based on the following areas where paraquat dichloride was believed to
exceed the risk criteria under 40 CFR 162.11: teratogenicity, lack of emergency
treatment, chronic effects, reproductive effects, oncogenicity (data gap), mutagenicity
(data gap), and acute effects. Other areas of concern included mammalian toxicity and
avian reproductive effects. Upon conclusion of the Special Review evaluation in
October 1982 (43 FR 30613), the Agency issued a Final Position Document which
concluded that the available data did not support paraquat dichloride being placed into
the Special Review status since the risk criteria identified in 1978 had not been
exceeded.
After the Special Review evaluation, the Agency believed that the acute effects
level was very close to estimated applicator exposures. Therefore, a Data Call-in was
issued for paraquat dichloride requiring additional dermal and inhalation data and
more precise information to assess the potential of acute effects as a result of
applicator exposure to this compound. A Registration Standard for paraquat
dichloride was issued in June 1987 (NTIS #PB 88-217005) in which the Agency
-------
evaluated the studies submitted as a result of the previous DCI. This Reregistration
Eligibility Decision reflects a reassessment of all data which were submitted in
response to the Registration Standard and subsequent December 1991 DCI.
DI. SCIENCE ASSESSMENT
A. Physical Chemistry Assessment
Paraquat dichloride (l,r-dimethyl-4,4t-bipyridinium dichloride) is a
nonselective contact herbicide, desiccant, defoliant, and plant growth regulator
primarily used on field crops and fruit and nut crops.
-CE,
2cr
Empirical Formula: C,2H,4C12N2
Molecular Weight: 257.2
CAS Registry No.: 1910-42-5
OPP Chemical Code: 061601
Production of the paraquat dimethyl sulfate salt [l,r-dimethyl-4,4'-
bipyridinium bis(methyl sulfate); OPP Chemical Code 061602] has been discontinued;
there are no active uses or products.
IDENTIFICATION OF ACTIVE INGREDIENT
Paraquat dichloride is an off-white, odorless hygroscopic (holding moisture)
powder with a melting point of approximately 340 C. Paraquat dichloride is freely
soluble in water, slightly soluble in alcohols, and insoluble in nonpolar organic
solvents. The Technical Grade Active Ingredient (TGAI) is corrosive to metals,
hydrolyzes under alkaline conditions, and decomposes photochemically.
MANUFACTURING-USE PRODUCTS
There are two paraquat'dichloride manufacturing-use products (MPs) registered
to Zeneca AG Products under OPP Chemical Code 061601; they are the 43.5%
formulation intermediates (FIs) (EPA Reg. Nos. 10182-115 and 10182-362).
10
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B. Human Health Assessment
1. Toxicology Assessment
The toxicological data base for paraquat dichloride is adequate and will
support reregistration eligibility.
a. Acute Toxicity
The table below defines the different Acute Toxicity Categories
for the different routes of administration.
Hazard
Indicators
Oral LD50
Inhalation LC50
Dermal LD50
Eye Effects
Skin Effects
*"l~~" , * % Acute Toxicjty Categories r ~* '-,
Category I =
very highly or
highly toxic
*' *-^,'
Up to and including
50 mg/kg
Up to and including
0.05 mg/L
Up to and including
200 mg/kg
Corrosive; corneal
opacity not
reversible within
21 days
Corrosive
Category II =
moderately
toxic
/, v~ >-"
From 50 thru 500
mg/kg
From 0.05 thru 0.5
mg/L
From 200 thru
2000 mg/kg
Corneal opacity
reversible within 8-
21 days
Severe irritation at
72 hours
Category III =
slightly toxic
~_v
\
From 500 thru 5000
mg/kg
From 0.5 thru 5.0
mg/L
From 2000 thru
5000 mg/kg
Corneal opacity;
irritation reversible
within 7 days
Moderate irritation
at 72 hours
Category IV
= practically
non-toxic
\ *~ ~
Greater than 5000
mg/kg
Greater than 5.0
mg/L
Greater than 5000
mg/kg
Corneal opacity
cleared within 24
hours
Mild or slight
irritation at 72
hours
The table below summarizes the acute toxicity studies on
paraquat dichloride and the Toxicity Categories for the different routes
of administration.
11
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ACUTE TOXICITY DATA FOR PARAQUAT DICHLORIDE
TEST
Acute oral LDM
(rat)
Acute Dermal LDM
(Rat)
Acute Inhalation
LCs,(Rat)
Eye Irritation
(Rabbit)
Dermal Irritation
(Rabbit)
Dermal Sensitization
(Guinea pig)
RESULTS
344 mg/kg e?
283mg/kg?#
>2000mg/kg#
1 ugflL ds-ฅ m
Moderate to severe
irritation #
Minimal irritation;
PIS = 0.5 #
Negative #
1 '" .-1
CATEGORY ,
II
m
I
n
rv
--
MRTDl^o, , 1
43685001
43685002
00046105
43685003
43685004
43685005
# The test material used in these studies was paraquat technical concentrate which is 45.6% paraquat dichloride (cation
content: 33% \v/w). The LDM values are expressed in terms of paraquat dichloride (and not as paraquat cation).
## The test material used in this study was crystalline paraquat dichloride. Purity was not specified, but crystalline
paraquat dichloride used in other studies was 99.9% pure. The LQ0 value is expressed as paraquat dichloride (and
not as paraquat cation).
The following toxic signs were observed in the'above studies:
Acute-Oral LD50 (Rat): Decreased activity, dehydration, hypothermia,
irregular breathing, chromodacryorrhea, piloerection, sides pinched in,
stains around nose and mouth, upward curvature of the spine, reduced
splay reflex and mottling and dark areas in the lungs. Doses tested:
100,250,400 or 600 mg/kg, in SPF Wistar-derived male and female
rats.. (MRID 43685001)
Acute Dermal LD50 (Rat): Slight or moderate skin irritation (edema
and/or erythema), and scabbing and thickening of the skin at the
application site. There was no mortality. Dose tested: 2000 mg/kg
(limit dose), in SPF Wistar-derived male and female rats (intact skin,
24-hour contact period). (MRID 43685001)
Acute Inhalation LC50 (Rat): Pale and swollen kidneys, and lung
changes (congestion, occasional petechial hemorrhages, and increased
number of polymorphs and histiocytes around the bronchi and vessels)
all at the two highest concentrations tested. Concentrations tested
(analytical values): 0.4, 0.75,1.3, 1.5,2.6,4.8,13.7 and 32.5 ug/L,
expressed as paraquat dichloride, in Alderley Park SPF rats. 6-Hour
exposure to respirable particles [2.5 u or smaller]. (MRID 00046105)
12
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Primary Eye Irritation (Rabbit): Corneal effects (slight or mild opacity
involving 1/4-1/2 of the cornea), cleared by day 17; and conjunctival
effects (slight to severe redness and discharge, and slight to mild
chemosis). Regression times (days after dosing): chemosis, 14;
redness, 28 (end of study); and discharge, > 28 (still present in 2/3 of
the surviving rabbits at the termination of the study. Dose tested: 0.1
mL of the undiluted test material, in 3 young adult female New Zealand
White rabbits (unwashed eyes, Draize scoring). Moderate to severe
ocular irritant = class 5 on a scale of 1-8. (MRID 43685003)
Primary Dermal Irritation (Rabbit): Very slight erythema in all 3 rabbits
(score 0.7-1.0 on a scale of 0-4); very slight edema in 1 rabbit (score 1.0
on a scale 0-4); and desquamation, thickening, and scabbing in 1 rabbit.
Regression times: erythema, in 2-3 days after dosing (2 rabbits) and in
27 days (1 rabbit); edema, in 7 days; and other signs, in 34 days (end of
study). Primary dermal irritation score 0.5 at 72 hours. Dose tested:
0.5 mL of undiluted test material, in 3 young adult female New Zealand
White rabbits (4-hour exposure, intact skin, Draize scoring). (MRID
43685004)
Dermal Sensitization (Guinea Pig): Not a skin sensitizer under the
conditions of the maximization test of B. Magnusson and A.M. Kligman
(Allergic Contact Dermatitis in the Guinea Pig; 1970). Positive control
used: 2-mercaptobenzothiozole. (MRID 43685005)
b. Subchronic Toxicity
90-Day Feeding. Non-Rodent:
In a repeated dose oral toxicity study, male and female beagle
dogs, 3/sex/group, received paraquat dichloride for 13 weeks at the
following levels, expressed as paraquat cation: 0, 7, 20, 60 or 120 ppm
(0, 0.18, 0.5, 1.5 or 3.0 mg/kg/day, respectively). The test material,
added to the diet, was the technical grade aqueous solution containing
32.2% w/w of paraquat cation. The dogs, aged 7-8 months at the start
of the study, were given 400 g of the appropriate diet mix every
morning. Any remaining food was removed and weighed the following
morning. At the 7 ppm (0.18 mg/kg) and the 20 ppm (0.5 mg/kg)
levels, paraquat had no effect on any of the parameters examined.
Toxic signs observed in the 60 ppm (1.5 mg/kg) group included
increased absolute (39-41%) and relative (44-56%) lung weight,
alveolitis and alveolar collapse. Unless stated otherwise, the following
treatment-related symptoms were observed in both sexes at the 120 ppm
(3.0 mg/kg) level: weight loss (4-8%), decreased food intake (22-67%)
13
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for one surviving female during the last 6 weeks of the test, increased
absolute (75-76%) and relative (92-104%) lung weight, marked
dyspnea, harsh rales, slow and/or irregular heart beat, large lesions in
the lungs (alveolitis), alveolar collapse and high mortality (2/3 males
and 2/3 females during study days 16-23). Based on the above
findings, the NOEL and LOEL for systemic toxicity, for both sexes, are
20 ppm (0.5 mg/kg/day) and 60 ppm (1.5 mg/kg/day), respectively.
Although there was a 12% weight loss (PO.01) in the female 20 ppm
group during week 13, this loss was greater than that observed in the 60
ppm and 120 ppm groups, and, therefore, did not appear to be
treatment-related. (MRID 00072416)
21-Day Dermal Toxicitv. Rabbit:
In a repeated dose dermal toxicity study, male and female New
Zealand white rabbits, 6/sex/group, were exposed (intact skin) to
paraquat dichloride (cation content: 43.5%) for 21 consecutive days (6
hours/day). Paraquat dichloride was applied as an aqueous solution (1.0
mL/kg b.w.) at the following concentrations: 0,1.5, 3.4, 7.8 or 17.9
mg/kg/day (0, 0.5,1.15, 2.6 or 6.0 paraquat cation, respectively).
Treatment-related effects were observed only at the two highest
concentrations tested. In the 2.6 mg cation/kg group, scabbing at the
dosing site was seen in two males and one female. The following toxic
signs were observed in the 6.0 mg cation/kg group, in all rabbits, at the
dosing site: scabbing; slight to well-defined erythema; minimal to
moderately severe inflammation, acanthosis and hyperkeratosis (females
only); slight to severe erosion/ulceration and surface exudate; and
decreases in absolute weight (18%) and relative weight (organ/body
weight and organ/brain weight ratios; 17-22%) of testes. No gross
histological changes were found in the lungs, the target organ for
paraquat. Based on dermal irritation, the NOEL and LOEL are,
respectively, 1.15 mg/kg/day and 2.6 mg/kg/day, expressed as paraquat
cation. (MRID 00156313)
21-Day Inhalation Toxicity. Rat:
In a repeated dose inhalation toxicity study, Sprague-Dawley rats
were exposed (whole body) to respirable aerosols of paraquat dichloride
(cation content: 40%; particle size: < 2 urn in diameter) for 3 weeks (6
hours/day, 5 days/week). The concentrations of paraquat cation in the
inhalation chambers were 0, 0.01, 0.1, 0.5 and 1.0 ug/L (nominal) or 0,
0.012, 0.112, 0.487 and 1.280 ug/L, respectively, (analytical). The
numbers of rats of each sex assigned to these groups were as follows:
14
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32 (control group), 16 (0.5 ug/L group) and 36 (remaining groups).
Parameters examined included observations for toxic signs, body
weights and food consumption. One-half of the rats in each group were
examined grossly and microscopically after 15 exposures and the
remaining rats were examined 2 weeks after the termination of the
exposures (recovery period). These examinations were restricted only
to the respiratory tract (nasal passages, pharynx, tongue, larynx, trachea
and lungs). The 1.0 ug/L group was abandoned after the first exposure
because 28 males (78%) and 29 females (80%) died from respiratory
failure after that exposure.
Toxic signs were not observed in the 0.01 ug/L group and there
was no mortality in this or the other test groups. All rats in the 0.1 ug/L
group had nasal discharge and squamous keratinizing metaplasia, and/or
hyperplasia of the epithelium of the larynx. The changes in the
ephithelium were still observed in 69% of the rats sacrificed at the end
of the recovery period. The following findings were reported for the 0.5
ug/L group examined after 3 weeks of treatment: (1) extensive
ulceration, necrosis, inflammation and squamous keratinizing
metaplasia, and marked/moderate hyperplasia of adjacent epithelia in
the larynx of all rats; and (2) aggregations of foamy macrophages in the
bronchioles or alveoli, hypertrophy of the epithelium and thickened
alveolar walls in the lungs of most or all rats. After a 2-week recovery
period, no ulceration or necrosis was observed in the larynx, but
changes in the lungs were still seen. In addition, disruption of
bronchiolar epithelium, adjacent to the macrophage aggregation, was
noted.
Considering the above findings, the NOEL and LOEL for sub-
chronic (3 weeks) inhalation toxicity, for both sexes, are 0.01 ug/L and
0.10 ug/L, respectively, expressed as paraquat cation. (MRID
00113718)
c. Chronic Toxicity
Chronic Toxicitv/Oncogenicitv. Rodent:
In this chronic feeding/carcinogenicity study, Fischer 344 rats,
80/sex/group, were fed diets containing paraquat dichloride (cation
content: 32.69%) for 113-117 weeks (males) and 122-124 weeks
(females). Based on the results of a preliminary study, the doses of
paraquat selected for this study were 0 (Group 1), 0 (Group 2), 25
(Group 3), 75 (Group 4) or 150 ppm (Group 5), expressed as paraquat
cation (nominal concentrations). Assuming that, for an older rat, 1 ppm
15
-------
= 0.05 mg/kg/day, these doses corresponded to 0, 0, 1.25, 3.75 or 7.5
mg of paraquat cation/kg/day, respectively. Twenty rats from each
group (10 of each sex) were sacrificed after one year of treatment: 5 of
each sex/group, for the usual interim sacrifice and another 5 of each
sex/group, to determine paraquat concentration in tissues. According to
the initial protocol, this study was to be terminated after 104 weeks.
However, because of the low number of deaths during that period, the
study was extended until survival was reduced to 50%in any one of
Groups 1-4 (Group 5 was excluded from consideration).
Starting with the test week 6, the female rats at all dose levels
ingested more paraquat (15-33%) per kilogram of body weight than did
the male rats at the same dose levels. With the exception of minimal
lens opacities in 3/60 (5%) males and 6/60 (10%) females, nothing
remarkable was observed in the 25 ppm group. Since these incidences
were only 1% and 3% higher than in the control males and females,
respectively, and occurred mostly after week 104, they appeared to be
an acceleration of the normal aging process and not a qualitatively
different effect.
The only treatment-related statistically significant effects
observed in the 75 ppm group, were increased incidence of (1)
opacities/cataracts in the males (4%) and the females (19%, P< 0.01);
(2) ptosis/swollen eyelids in the females (7%); and (3) non-neoplastic
lung lesions in the male nonsurvivors (alveolar macrophages; 14%,
P<0.05). In the case of the ocular lesions, there were about as many
opacities as there were cataracts.
In the 150 ppm group, the incidence of eye opacities/cataracts
was 37% (controls, 4%) in the males and 58% (controls, 4%) in the
females. Only one opacity and all cataracts were observed in each male
and female high-dose groups. Compared with the controls, other
findings observed in the 150 ppm group were (1) slight decreases in the
food consumption for the males (3-7%) and the females (3-8%) during
most of the study; (2) decreased body weight gain during weeks 11-68
for the males (10-34%) and during weeks 27-78 for the females (11-
34%); (3) decreased food utilization for the males (12-21%) and females
(11-13%) during weeks 13-52; (4) increased relative weight of the lungs
(lung/body weight ratio) in the males (16%, PO.05) and the females
(14%, P<0.05) sacrificed at the termination of the study; (5) increased
incidence of hydrocephalus in the females sacrificed at the termination
of the study (36%, PO.01); (6) increased incidence of alveolar
macrophages in the male nonsurvivors (25%, PO.01) and in rats
16
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sacrificed at the termination of the study (males, 30% and females,
17%); and (7) increased incidence of alveolar epithelization (12%) and
slight peribronchial lymphoid hyperplasia (26%, PO.05) in the males at
the termination of the study.
The above findings show that paraquat enhanced the
development of ocular lesions in all of the treated groups. The
predominant lesions detected ophthalmoscopically were lenticular
opacities and cataracts. These lesions were either not observed or were
observed infrequently before the week 103. At test week 103, dose-
related statistically significant (PO.001) increases in the incidence of
ocular lesions were observed only in the mid-dose and high-dose male
and female groups. Based on these findings, the NOEL (approximate)
and the LOEL for systemic toxicity, for both sexes, are 25 ppm (1.25
mg/kg/day) and 75 ppm (3.75 mg/kg/ day), respectively. (MRID
00138637)
In another chronic feeding/carcinogenicity study, Wistar strain
rats, 62/sex/group, were fed diets containing technical grade paraquat
dichloride (purity: 98%) for 104 weeks. Based on the results of a
preliminary study, the doses of paraquat selected for this study were 0,
6, 30, 100 or 300 ppm, expressed as paraquat dichloride (nominal
concentrations). These values were equivalent to 0, 0.25,1.26, 4.15 or
12.25 mg/kg/day, respectively (males) and 0, 0.30, 1.50, 5.12 or 15.29
mg/kg/day, respectively (females), expressed as paraquat dichloride
(analytical concentrations). The interim sacrifices, using 6 rats/sex/
group, took place after 26 and 52 weeks of treatment.
Findings different from those in the controls were observed only
in the 300 ppm group and included (1) increased mortality in males
(66%; controls, 40%) and females (52%; controls, 42%); (2) decreased
erythrocytes, hemoglobin, and serum protein hi males and females; (3)
decreased hematocrit, glucose and corpuscular cholinesterase activity in
males (7.9% at week 52); (4) decreased leucocytes, albumin/globulin
ratio and alkaline phosphatase (34%), GOT (glutamic-oxaloacetic
transaminase, 18%) and GPT (glutamic-pyruvic transaminase, 23%)
activities in females; (5) increased polymorphonucleocytes in males; (6)
increased potassium and glucose in females; (7) decreased absolute
and/or relative weights of heart in males (10%) and females (14%); and
liver (14%) and brain (8%) in females; and (8) decreased absolute
weights of kidneys in males (13%) and females (17%), and ovaries (32-
17
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Ocular changes were not detected before the initiation of
treatment. After the treatment was started, cataracts were observed
during each examination (weeks 26, 52 and 104) in 1 to 4 rats per
group, including controls. At test weeks 52 and 104, corneitis (keratitis)
and conjunctivitis were also observed in all groups, including controls.
In this study, the incidence of ocular changes was low and dose-
unrelated. Considering the test weeks 26-104, the incidence of ocular
changes in the male and female treated rats was as follows: cataracts,
1.6-17.6% (controls 1.6-13.8%); corneitis, 0-5.9% (controls, 0-6.7%);
and conjunctivitis, 0-5.4% (controls, 0-6.7%). Ocular changes,
therefore, do not appear to be caused by paraquat in this study.
Based on the above findings, the systemic NOEL is 100 ppm of
paraquat dichloride (4.15 and 5.12 mg/kg/day, for males and females,
respectively); or 3.0 mg/kg/day (males) and 3.7 mg/kg/day (females),
expressed as paraquat cation. The systemic LOEL is 300 ppm of
paraquat dichloride (12.25 and 15.29 mg/kg/day, for males and females,
respectively); or 9.0 mg/kg/day (males) and 11.2 mg/kg/day (females),
expressed as paraquat cation.(MRID 402J8001)
Chronic Toxicity. Non-Rodent:
Groups of 6 male and 6 female Alderley Park beagle dogs were
fed diets containing technical grade paraquat dichloride (cation content:
32.3%) for 52 weeks. The amount of food offered daily each dog was
400 g. The dose levels used were 0,15, 30 or 50 ppm, expressed as
paraquat cation. Based on the actual group mean body weights and
food consumption, these doses corresponded to 0, 0.45, 0.93 or 1.51 mg
of paraquat cation/kg/day, respectively, in the case of male dogs. For
female dogs, these doses corresponded to 0, 0.48, 1.00 or 1.58 mg or
paraquat cation/kg/day, respectively. The doses used in this study were
based on the results obtained in the 90-day feeding study (MRID
00072416) which has been discussed in the subchronic toxicity section
of this document.
The major effect of paraquat was a dose-related increase in the
severity and extent of chronic pneumonitis in the mid-dose and high-
dose male and female dogs. This effect was noted also in the low-dose
male group, but was minimal when compared with the male controls.
Chronic pneumonitis was less severe in the low-dose female group than
in the female controls. Because 44 dogs (out of 48 studied), including 6
male and 5 female controls, had some degree of chronic pneumonitis,
paraquat had no effect on the incidence of this lesion. Other findings
18
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observed only in the high-dose dogs were (1) significant (PO.01)
increases in the group mean lung weights (absolute or adjusted for body
weight, 36% in males and 61% in females) and in spleen weights
(absolute or adjusted for body weights, 50-55% in males and 38-43% in
females), when the paraquat-treated dogs were compared with the
controls; (2) hyperpnea in 67% males and females; and (3) increased
vesicular sound in 50% males and 67% females. Only one lenticular
cataract (minimal, in a mid-dose female) was observed in this study.
Based on the above findings, the systemic NOEL is 15 ppm (males:
0.45 mg/kg/day and females: 0.48 mg/kg/day, expressed as paraquat
cation). The systemic LOEL is 30 ppm (males:0.93 mg/kg/day and
females: 1.00 mg/kg/day, expressed as paraquat cation). (MRID
00132474)
d. Carcinogenicity
The Agency has received and reviewed four carcinogenicity
studies as are detailed below.
Chronic Feeding/Carcinogenicitv Study with Fischer 344 Rats
In this chronic feeding/carcinogenicity study, Fischer 344 rats,
80/sex/group, were fed diets containing paraquat dichloride (cation
content: 32.69%) for 113-117 weeks (males) and 122-124 weeks
(females). Based on the results of a preliminary study, the doses of
paraquat selected for this study were 0 (Group 1), 0 (Group 2), 25
(Group 3), 75 (Group 4) or 150 ppm (Group 5), expressed as paraquat
cation (nominal concentrations). Assuming that, for an older rat, 1 ppm
= 0.05 mg/kg/day, these doses corresponded to 0, 0, 1.25, 3.75 or 7.5
mg of paraquat cation/kg/day, respectively. Twenty rats from each
group (10 of each sex) were sacrificed after one year of treatment: 5 of
each sex/group for the usual interim sacrifice, and another 5 of each
sex/group, to determine paraquat concentration in tissues. According to
the initial protocol, this study was to be terminated after 104 weeks.
However, because of the low number of deaths during that period, the
study was extended until survival was reduced to 50% in any one of
Groups 1-4 (Group 5 was excluded from consideration). Gross
necropsy was performed on all rats on the study. With the exception of
the rats which were used for the determination of paraquat concentration
in tissues, all rats on the study were also examined microscopically.
During the initial review of this study, there were concerns that
paraquat might be carcinogenic in the rat. There was a dose-related
19
-------
increase in the incidence of pulmonary neoplasms (adenomas and
carcinomas), but especially adenomas, in the male and female rats. The
incidence of pulmonary neoplasms was 2.9, 5.7, 8.6 and 10.1% in the
control, low-dose, mid-dose and high-dose male groups, respectively.
The corresponding values for the female groups were 0, 2.9, 4.3 and
14.3%, respectively. A statistically significant (PO.001) increase was
observed only in the pulmonary adenomas and only in the high-dose
female rats. Most of the neoplasms were observed at the termination of
the study. However, there were difficulties in characterizing pulmonary
lesions as non-neoplastic or neoplastic, or as adenomas or carcinomas
and lung tissue was, therefore, examined by four independent
pathologists. Following submission of these data to the Agency, the
lung tissue was then reexamined by two additional pathologists, one
designated by the registrant and another by the Agency. The findings of
these pathologists were very similar and were within the historical
incidence of adenomas and carcinomas. According to one pathologist,
the incidence of pulmonary adenomas and carcinomas in the control,
low-dose, mid-dose and high-dose male rats was 2.9, 5.7,2.8 and 5.8%,
respectively. The corresponding incidences for the female groups were
0,1.4,2.8 and 0%, respectively. According to another pathologist, the
incidence of pulmonary adenomas and carcinomas in these groups was
2.9, 5.7, 4.3 and 5.8%, respectively (males) and 0, 1.4, 2.8 and 2.8%,
respectively (females). Based on these findings, paraquat did not appear
to be carcinogenic in the lungs of rats.
There was a higher incidence of squamous cell carcinomas in the
head region (middle ear, hard palate, head tissue and skin), an
uncommon tumor, but the incidence was generally low and dose-
unrelated. The incidence of these carcinomas (combined) was 2.1, 4.3,
0 and 8.6% in the control, low-dose, mid-dose and high-dose male
groups respectively. The corresponding incidences for the female
groups were 0, 0, 4.3 and 2.9%, respectively. All of these carcinomas
occurred during the second year of study. The incidence of benign
pheochromocytomas in the adrenal medulla and perifollicular adenomas
and carcinomas in the thyroid was also increased in the high-dose male
rats. However, the relationship of these neoplasms to treatment was
unclear and additional data were, therefore, requested to evaluate
adequately the carcinogenic potential of paraquat in tissues other than
the lungs. An independent pathologist, selected by the Agency,
reviewed slides from the head region and concluded (as did the
registrant) that there was no justification for combining squamous cell
carcinomas (which occurred in four different sites of the head) for
assessment purposes. According to the pathologists (EPA's and the
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registrant's), the skin and oral and nasal cavities have different
morphology and physiology, and separate biological functions, and
cannot be considered as a single organ in terms of assessment of
carcinogenic effects. When each of these sites was considered
independently, in the accepted manner for assessing tumor incidence, in
no instance was there a statistically significant difference between the
treated and control rats. Paraquat was, therefore, not carcinogenic in the
head region of the rat.
The incidence of pheochromocytoma in the, adrenal gland of the
control, low-dose, mid-dose and high-dose male rats was 8.6, 12.6, 11.4
and 17.4%, respectively. The incidence of pheochromocytoma in the
historical control male rats ranged from 6.7% to 38.8% and this tumor
occurred in each of the eight studies from which historical data were
obtained. Considering the historical incidence, the incidence of
pheochromocytoma in this study (11.4-17.4%) did not appear to be
paraquat-related because it fell within the range reported for the
historical control male rats.
The incidence of parafollicular adenomas and carcinomas in the
thyroid gland of the concurrent control, low-dose, mid-dose and high-
dose male rats was 11.9, 16.9, 13.6 and 18.8%, respectively. The
incidence of these neoplasms in the historical control male rats ranged
from 13.3% to 35.4%. Considering the historical incidence, the
incidence of parafollicular adenoma and carcinoma in the high-dose
male rats (18.8%), in this study, did not appear to be treatment-related.
(MRIDs: 00138637, 00153223, 40202401, 40202402 and 41317401)
Chronic Feeding/Carcinogenicitv Study with Wistar Strain Rats
In another chronic feeding/carcinogenicity study, Wistar strain
rats, 62/sex/group, were fed diets containing technical grade paraquat
dichloride (purity: 98%) for 104 weeks. Based on the results of a
preliminary study, the doses of paraquat selected for this study were 0,
6, 30,100 or 300 ppm, expressed as paraquat dichloride (nominal
concentrations). These values were equivalent to 0, 0.25,1.26,4.15 or
12.25 mg/kg/day, respectively (males) and 0, 0.30, 1.50, 5.12 or 15.29
mg/kg/day, respectively (females), expressed as paraquat dichloride
(analytical concentrations). The interim sacrifices, using 6
rats/sex/group, took place after 26 and 52 weeks of treatment.
Paraquat was not carcinogenic in this study. Gross, non-
neoplastic and neoplastic lesions were observed in various organs of
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males and females, but did not appear to be treatment-related (either a
dose-relationship was lacking or the incidence was similar in the
controls and the paraquat-treated groups). The most frequent lesions
were observed in the following organs: (1) lungs (congestion, nodes,
peribronchiolitis, pneumonia and thickening of alveolar walls); (2) liver
(bile duct proliferation and fibrosis); (3) kidneys (rough surface and
nephritis); (4) pituitary (hypertrophy, hematoma and benign tumors); (5)
thyroid (benign tumors); (6) adrenals (cysts); (7) spleen (swelling);
(8) mesenteric lymph node (swelling and inflammation); (9) testes and
ovaries (atrophy); (10) uterus (cysts and polyps); and (11) mammary
glands (cysts, adenomas, fibromas, fibroadenomas and
adenocarcinomas). (MRID 40218001)
Chronic Feeding/Carcinogenicity Study with SPF Swiss-Derived Mice
Groups of SPF Swiss-derived mice (Alderley Park strain),
60/sex/dose, were administered paraquat dichloride (cation content:
32.7%) for 23 months (when mortality was approaching 80% in all
groups). The dose levels used in this study were 0 (two control groups),
12.5, 37.5 or 100/125 ppm, expressed as paraquat cation, and were
based on the results of two preliminary (28-day) studies (MRID
00087921 and 00087922). Assuming that, for a mouse, 1 ppm = 0.15
mg/kg/day, these doses corresponded to 0,1.87, 5.6 or 15.0/18.7 mg of
paraquat cation, kg/day, respectively. Because no toxic signs appeared
after 35 weeks of dosing, the 100 ppm level was increased to 125 ppm
at week 3 6.
Nothing remarkable was observed in the low-dose male and
female group. Toxic signs observed in the mid-dose group included (1)
decreased food consumption (15-22%) in the females during weeks 56-
84, when compared with the controls; (2) decreased body weight gain
(5-7%) in the females during weeks 68-88; and (3) renal tubular
degeneration in the males (nonsurvivors, 40% and at the terminal
sacrifice, 38%). Toxic signs observed in the high-dose group included
(1) decreased food consumption in the males (7-15%) during weeks 4-
24 and in the females (8-34%) during weeks 5-88, when compared with
the controls; (2) decreased body weight gain in the females (12-45%)
during weeks 44-96; and (3) renal tubular degeneration in the males
(nonsurvivors, 65% and at the terminal sacrifice, 67%) and the females
(nonsurvivors, 50% and at the terminal sacrifice, 63%). A high
incidence of lenticular changes (degeneration, swelling and lens fibers
broken up into eosinophilic globules) were observed in the control and
paraquat-treated male and female mice, in both the nonsurvivors (81-
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93%) and at the termination of the study (92-100%). This finding was
surprising, but special staining and fixation techniques were not used to
distinguish true pathological changes from artifacts in the eye tissue.
The incidence of cataracts was low (males, 0-8% and females, 0-21%)
and dose-unrelated.
Paraquat was not carcinogenic in this study. Paraquat, at all
levels tested, had no effect on the incidence of benign and malignant
neoplasms in both male and female mice. The most prevalent benign
neoplasms were lung adenomas and Harderian gland adenomas in the
males and the females, pituitary adenomas in the females, and liver
nodules (Type A) in the males. The most prevalent malignant
neoplasms were lymphosarcomas in the males and females, and liver
nodules (Type B) in the males.
Based on the above findings, the systemic NOEL for both sexes
is 12.5 ppm (1.87 mg/kg/day) and the systemic LOEL is 37.5 ppm (5.6
mg/kg/day), each expressed as paraquat cation. (MRID 00087924)
Chronic Feeding/Carcinogenicitv Study with Groups of JCL:ICR Mice
Groups of JCL:ICR mice (Japan Clea Laboratories Co., Tokyo),
80/sex/dose, were administered paraquat dichloride (purity: 98%) for
104 weeks. Based on the results of a preliminary study (not submitted),
the doses of paraquat dichloride selected for this study were 0, 2, 10, 30
or 100 ppm (nominal concentrations). These values were equivalent to
0, 0.26, 1.31, 3.92 or 13.09 mg/kg/day, respectively (males) and 0, 0.26,
1.32, 3.82 or 13.03 mg/kg/day, respectively (females), expressed as
paraquat dichloride (analytical concentrations). The interim sacrifice,
using 10 mice/sex/group, took place after 26 and 52 weeks of treatment.
Treatment-related findings were observed only in the 100 ppm
group and included (1) increased mortality in the females; (2) decreased
total protein, erythroeytes, leukocytes, hemoglobin and hematocrit in
the males and females; (3) decreased polymorphonucleocytes in the
males and GPT and alkaline phosphatase activities in the females; (4)
decreased absolute and/or relative weights of adrenals, thyroid, liver and
urinary bladder in the males; (5) decreased absolute weight of brain in
the females; and (6) increased absolute and/or relative weights of
kidneys, lungs and heart in the males.
Paraquat was not carcinogenic in this study. Gross, non-
neoplastic and neoplastic lesions were observed in various organs of the
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male and female mice, but were not treatment-related. The most
frequent lesions were observed in the following organs: (1) lungs
(congestion, nodes, pneumonia, thickening of alveolar walls and
adenocarcinoma, all in both sexes); (2) liver (dilatation in the females
and tumors in the males); (3) kidneys (discoloration and coarse surface
in both sexes; dilatation of renal pelvis and cell infiltration in the males;
and nephropathy in the females); (4) spleen (swelling in both sexes); (5)
thymus (atrophy hi both sexes and hypertrophy in the females); (6)
mesenteric lymph node (swelling and cell infiltration in both sexes); and
(7) eyes (corneal cell proliferation in both sexes and corneal
calcification in the females). Leukemia, amyloid degeneration and
leukemia cell infiltration were also observed frequently in the males and
females.
Based on the above findings, the systemic NOEL is 30 ppm of
paraquat dichloride (3.92 and 3.82 mg/kg/day, for males and females,
respectively); or 2.9 mg/kg/day (males) and 2.8 mg/kg/day (females),
expressed as paraquat cation. The systemic LOEL is 100 ppm of
paraquat dichloride (13.1 mg/kg/day, for both sexes); or 9.4 mg/kg/day,
expressed as paraquat cation. (MRID 40202403)
The carcinogenic potential of paraquat was evaluated by the
Toxicology Branch Peer Review Committee (now Carcinogenicity Peer
Review Committee) in 1986, 1988 and 1989, and by the FIFRA
Scientific Advisory Panel (SAP) in 1989.
The first Committee classified (July 9, 1986) paraquat as a
Category C carcinogen (limited evidence of carcinogenicity in animals),
without the Q* (developing of a quantitative estimation of the
carcinogenic potential). This decision was based on an increased
incidence of squamous cell carcinoma, an uncommon tumor, in the head
region (ear, skin, and oral and nasal cavities) of the high-dose male
Fischer 344 rats, when the treated animals were compared with the
concurrent or the historical controls (Study No. 82/ILY 217/328; MRID
00138637). The registrant contended that those tumor sites should not
be combined and an independent laboratory, which re-evaluated the
data, agreed with the registrant. When each of these sites was
considered separately, there was no statistically significant difference in
the incidence of squamous cell carcinomas between the treated and
control rats.
Considering the above findings and the subsequent (negative)
carcinogenicity studies with rats and mice (MRIDs 40218001 and
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40202403, respectively), the second Committee placed paraquat in
Category E (no evidence of carcinogenicity in animal studies) on June
15, 1988.
The Federal Insecticide, Fungicide and Rodenticide Act (FIFRA)
SAP met on February 15, 1989 and, considering a squamous cell
carcinoma in the nasal cavity of two high-dose rats as an equivocal
evidence of carcinogenicity, placed paraquat in Category D. However,
the SAP also commented that further testing was not required and that
endpoints other than carcinogenicity were more relevant for the
regulation of paraquat.
The third Toxicology Branch Peer Review Committee met on
March 15,1989 and decided to retain the Category E carcinogenicity
classification for paraquat.
e. Developmental Toxicity
The Agency has received and reviewed four developmental
toxicity studies as are detailed below.
Developmental Toxicitv Studies with Alderlev Park. Wistar-Derived
Rats
In a developmental toxicity study, paraquat dichloride (38.2%
purity as paraquat ion content) was administered to 24 female Alderley
Park, Wistar-derived (Alpk:APfSD) rats/dose by gavage in deionized
water at dose levels of 0, 1, 3, or 8 mg paraquat ion/kg/day from days 7
through 16 of gestation. The developmental NOEL is 8 mg paraquat
ion/kg/day (HDT). (MRID 43964701)
No maternal or developmental effects were observed in the
study.
The maternal NOEL is 8 mg paraquat ion/kg/day (HDT).
In another study, paraquat dichloride (purity: 100%) was
administered by gavage in 0.5% aqueous Tween 80 to groups of 29-30
Alderley Park SPF rats at dose levels of 0, 1, 5 or 10 mg/kg/day,
expressed as paraquat cation, from gestation day 6 through 15. The test
solutions were administered in a volume of 1 ml/100 g of body weight.
Control females received the same volume of 0.5% Tween 80 alone.
Females were observed for changes in appearance or behavior and body
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weights were determined at intervals during gestation. The rats were
sacrificed on gestation day 21 and reproductive observations were made
and uteri examined for live fetuses and intra-uterine deaths. Fetuses
were weighed, sexed, and examined for external, visceral and skeletal
alterations. Doses used in this study were based on the results of a
range-finding study in which doses (paraquat cation) of 5,10, 20 or 40
mg/kg/day were tested and which was briefly summarized in this
submission. (In the range-finding study, all rats died in the 40 mg/kg
group and one rat died in the 20 mg/kg group. The nonsurvivors had
dark red lungs or dark red patches on the lungs).
Maternal toxicity was reported at the two highest doses and
included (1) clinical signs such as piloerection, thin and hunched
appearance, and decreased body weight gain (24% and 29% less than
controls for the mid-dose and high-dose groups, respectively); (2)
deaths of 6 high dose animals versus none in the control group; (3)
respiratory distress in 3 high-dose females; and (4) histopathological
findings in the lungs (edema in the alveoli and polymorph infiltration)
and in the kidneys (degenerative changes in the proximal tubules) of the
nonsurvivors.
Treatment-related developmental effects (delayed ossification in
the forelimb and hindlimb digits) were observed only in the mid-dose
and high-dose groups. It was reported that 41.9% of the control group
fetuses had good forelimb digit ossification compared with 28.8% and
23.0% of the mid-dose and high-dose fetuses, respectively. Similar
results were noted for the hindlimb digit ossification.
Based on the above findings, the NOEL and LOEL for maternal
toxicity are 1 mg/kg/day and 5 mg/kg/day, respectively, expressed as
paraquat cation. The NOEL and LOEL for developmental toxicity are
also 1 mg/kg/day and 5 mg/kg/day, respectively. (MRID 00113714)
The overall maternal NOEL for the rat is 3 mg/kg/day based on
the results from the two previously summarized studies (MRID's
43964701 and 00113714).
Developmental Toxicitv Study with CrlrCDl flCR) BR Mice
In another developmental toxicity study, paraquat dichloride
(38.2% purity as paraquat ion content) was administered to 26 female
Crl:CDl (ICR) BR mice/dose by gavage in water at dose levels of 0,
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7.5, 15 or 25 mg paraquat ion/kg/day from days 6 through 15 of
gestation.
At 25 mg/kg/day, paraquat is maternally toxic, inducing clinical
signs (piloerection, labored respiration, hunched posture, hypothermia,
hypoactivity and/or pale extremities and eyes); death; decreases in body
weight and body weight gain (p < 0.01); dark red lung lobes; increases
in lung with trachea and kidney weights and a possible decrease in
pregnancy rate. No maternal effects were observed at either 7.5 or 15
mg paraquat ion/kg/day.
At 25 mg/kg/day, significant decreases in mean fetal weights
were observed. In addition, skeletal effects were observed which
included increases in the number of litters with retarded ossification of
the occipital (p < 0.05), the number of fetuses and litters with ^ 6 caudal
centra (p < 0.01 and < 0.05 for fetuses and litters, respectively), the
number of litters with uni- or bilateral extra 14th ribs (p < 0.05) and the
number of fetuses and litters with non-ossified astragalus in the
hindlimb (p < 0.01 and < 0.05 for fetuses and litters, respectively). No
other developmental effects were observed at this dose level. No
developmental effects were observed at either 7.5 or 15 mg paraquat
ion/kg/day.
The maternal LOEL is 25 mg paraquat ion/kg/day, based on
clinical signs, death, decreases in body weight and body weight gain,
dark red lung lobes, increases in lung with trachea and kidney weights
and a possible decrease in pregnancy rate. The maternal NOEL is 15
mg/kg/day.
The developmental LOEL is 25 mg paraquat ion/kg/day, based
on decreases in mean fetal weights and retarded ossification of the
occipital, increases in the number with ฃ 6 caudal centra, increases in
the number with uni- or bilateral extra 14th ribs and increases in the
number with non-ossified astragalus in the hindlimb. The developmental
NOEL is 15 mg/kg/day. (MRID 43949902)
Developmental Toxicity Study with SPF Alderley Park Mice
In another study, paraquat dichloride (purity: 100%) was
administered by gavage in 0.5% aqueous Tween to groups of SPF
Alderley Park mice at dose levels of 0, 1, 5 or 10 mg/kg/day, expressed
as paraquat cation, from gestation day 6 through 15. The test solutions
were administered in a volume of 0.1 ml/10 g of body weight. Control
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animals received Tween 80 alone. The study was started with 120
mated mice, 30/dose. Because several mice in each group either were
not pregnant, died or littered (and were excluded from the study),
insufficient litters were available for examination. An additional 42
females were, therefore, mated 4-5 weeks after the first matings and
were allocated to the four test groups as follows: 6 each to the control
and the low-dose groups, 20 to the mid-dose group and 10 to the high-
dose group. The mice were sacrificed on gestation day 18. Maternal
parameters examined included body weight, clinical observations,
reproductive observations (resorptions, viable fetuses and number of
implantations), necropsy, and histopathology on the following tissues:
lungs, kidneys, heart, spleen, liver, ovaries, uterus and placenta. Fetuses
were weighed, sexed, and examined for external, visceral and skeletal
alterations. Doses used in this study were based on the results of a
range-finding study in which doses (paraquat cation) of 5, 10, 20 or 40
mg/kg/day were tested and which is briefly summarized in this
submission. (In the range-finding study, all mice died in the 40 mg/kg
group and one mouse died in the 10 mg/kg group. The nonsurvivors
had dark red lungs or dark red patches on the lungs).
The only possible treatment-related maternal toxicity observed
was a reduction in body weight gain in the mid-dose group (14%,
P<0.05) and the high-dose group (11%). However, in the range-finding
study with nonpregnant females, there was one death at 10 mg/kg/day.
In addition, there was a statistically significant increase in the number of
litters and fetuses with partially ossified 4th sternebrae in the high-dose
group. There was also a statistically significant increase in trend. This
is indicative of maternal toxicity. Gross necropsy and histopathology of
maternal tissues revealed no treatment-related abnormalities. The only
treatment-related developmental effect was the increase in the number
of litters and fetuses with partially ossified 4th sternebrae in the high-
dose group. Based on these findings, the NOEL and LOEL for maternal
toxicity are 5 mg/kg/day and 10 mg/kg/day, respectively, expressed as
paraquat cation. The NOEL and LOEL for developmental toxicity are
also 5 mg/kg/day and 10 mg/kg/day, respectively. (MRID 00096338)
f. Reproductive Toxicity
Wistar-derived Alderley Park strain of rats, 15 males and 30
females/group, were fed technical grade paraquat dichloride (cation
content: 32.7%) for 11-12 weeks before they were mated to produce F,,
F2 and F3 A litters, and subsequently F,, F2 and F3 A litters. The
following levels of paraquat cation were fed in the diet: 0, 25, 75 or 150
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ppm. Assuming that, for an older rat, 1 ppm = 0.05 mg/kg/day, these
doses correspond to 0, 1.25, 3.75 or 7.5 mg of paraquat cation/kg/day,
respectively. These doses are identical to those used in the chronic
feeding/carcinogenicity study with rats (MRID 00138637).
Paraquat, at all levels tested, had no effect on body weight gain,
food consumption and utilization, fertility and length of gestation of the
F0, FI and F2 parents. However, there was a high incidence of mortality
(27-43%) in the high-dose F0 F! and F2 females, due mostly to severe
lung damage caused by paraquat. The incidence of lung injury (red or
purple discoloration, congestion, edema, fibrosis, hyaline membrane
formation, inflammatory cell infiltration and/or hyperplasia) ranged
from 27% to 35%. There was also an increased incidence of alveolar
histiocytosis in the lungs of the mid-dose and high-dose male and
female parents. In the case of the F0 F! and F2 females, the incidence
was 28-40% (control groups), 28-54% (low-dose groups), 62-80%
(mid-dose groups) and 80-100% (high-dose groups). The
corresponding incidences for the males were 11-30%, 0-13%, 10-71%
and 50-86%, respectively.
The most frequent histological findings at the termination of the
study were hydronephrosis, nephrocalcinosis, lung congestion and/or
alveolar hemorrhage, perivascular inflammatory cell infiltration in the
lungs, focal accumulation of lymphocytes hi the liver, and hypoplasia,
atrophy and/or necrosis of the testes. However, the incidence of these
findings was not dose-related.
Based on the above findings, the NOEL and LOEL for systemic
toxicity are 25 ppm (1.25 mg/kg/day) and 75 ppm (3.75 mg/kg/day),
respectively, expressed as paraquat cation. The NOEL for reproductive
toxicity is k 150 ppm (7.5 mg/kg/day; HDT), expressed as paraquat
cation. (MRID 00126783)
g. Mutagenicity
Paraquat was weakly positive in the mouse lymphoma cell assay,
but only with metabolic activation (in the presence of Aroclor 1254-
stimulated rat hepatic microsomes, S-9, plus appropriate cofactors). It
induced forward mutation in the L5178Y mouse lymphoma cell line as
monitored by cell growth in the presence of trifluorothymidine (TFT).
Mouse lymphoma L5178Y cells were exposed for 2 hours to paraquat
dichloride (technical grade; active ingredient content: 45.7%) at
concentrations ranging from 31.25 to 1000 ug/mL, both in the presence
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and absence of the S-9 mix. Five separate experiments were performed.
Positive controls used were ethyl methane sulfonate (EMS) and
benzo(a)pyrene [B(aP]. Concentration-related cytotoxicity to paraquat
was observed in all experiments. Concentrations of 500-1000/mL were
either severely cytotoxic or lethal. This study satisfies Guideline
requirements for genetic effects, Gene Mutations. (MRID 00152690)
Paraquat dichloride (purity: 99%) was not mutagenic in the
Ames test using Salmonella typhimurium histidine-requiring strains
TA1535, TA1538, TA98 and TA100, with and without metabolic
activation. The concentrations of paraquat dichloride tested were 0.16,
0.8, 4, 20,100, 500, 2500 and 5000 ug/plate. Concentrations above 100
ug/plate were cytotoxic. Positive controls used were N-2-
acerylaminofluorene (AAF), 2-nitrofluorene (2NF), 2-(l-chloro-2-
isopropylaminoethyl) naphthalene (CPE) and meclorethamine (nitrogen
mustard). This study satisfies Guideline requirements for genetic
effects, Gene Mutations. (MRID 00100441)
Paraquat was weakly positive in the mammalian cells (human
lymphocytes) in culture cytogenetic assay, with and without metabolic
activation (S-9 mix). The lymphocytes were obtained from two healthy
donors, male and female. The concentrations of paraquat dichloride
(analytical grade; active ingredient content: 99.6%) tested ranged from
0.75 to 3500 ug/mL. Positive controls used were mitomycin-C (MC)
and cyclophosphamide (CP). Severe cytotoxicity was observed in
cultures exposed to the highest concentration of paraquat tested (3500
ug/mL). Concentration-related decreases in mitotic indices were
recorded at 125-2500 ug/mL. Increases in chromosome damage were
found in non-activated cultures exposed to the 1250 ug/mL and higher
levels of paraquat. In the presence of S-9, statistically significant
(P<0.01) increases in chromosome damage were observed at 1750
ug/mL in the case of one donor and at 2500 ug/mL in the case of
another donor. This study satisfies Guideline requirements for genetic
effects, Structural Chromosome Aberrations. (MRID 00152692)
Analytical grade paraquat dichloride (active ingredient con-tent:
99.4%) was positive in the sister chromatid exchange (SCE) assay, with
and without metabolic activation. Duplicate mono- layer cultures of
DON cells (derived from Chinese hamster lung fibroblasts) were
exposed for 3 hours to paraquat dichloride ranging in concentration
from 1.2 to 2470 ug/mL, with and without the metabolic activation
system (S-9). Cell cultures were then incubated with brom
deoxyuridine for 20 hours, incubated with cholchicine for 2 hours and
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then processed for microscope slide scoring for SCE according to
standard procedures. Mitomycin C (MC) and cyclophosphamide (CP)
were used as positive controls. This study satisfies Guideline
requirements for genetic effects, Structural Chromosome Aberrations.
(MRID 00152695)
Technical grade paraquat dichloride (cation content: 33%) was
negative for chromosomal aberrations in the bone marrow test system.
Positive results were obtained with cyclophosphamide, a known
clastogen. In this study, Alderley Park Wistar-derived male and female
rats received by gavage single doses of paraquat dichloride and then
were sacrificed for bone marrow sampling at 12, 24 or 48 hours after
treatment. The doses used, expressed as paraquat cation, were 0,15, 75
or 150 mg/kg. Based on the results from a preliminary study, the 150
mg/kg dose approximated a maximum tolerated dose (MTD). This
study satisfies Guideline requirements for genetic effects, Structural
Chromosome Aberrations. (MRID 40202405)
No evidence of dominant lethal mutagenicity or suppression of
fertility was seen in the study with CD-I mice. In this study, male mice
were administered paraquat dichloride (cation content: 28.3%) by
gavage for 5 consecutive days and then were mated with different
untreated female mice for 8 weeks. The doses of paraquat used were 0,
0.04, 0.4 and 4.0 mg/kg, expressed as paraquat cation. These doses
were based on the results of a preliminary study in which the 4.0 mg/kg
dose was the maximum tolerated dose (MTD). Mutagenic effects were
observed with positive controls, ethyl methane sulphonate (EMS) and
cyclophosphamide (CP). This study satisfies Guideline requirements
for genetic effects, Structural Chromosome Aberrations. (MRID
00100442)
Analytical grade paraquat dichloride (active ingredient content:
99.6%) did not induce unscheduled DNA synthesis in rat hepatocytes
exposed in vitro. Hepatocytes from an untreated male rat (Alderley
Park SPF albino) were allowed to attach to cover slips for 2 hours and
then were exposed for 19 hours to tritiated thymidine together with
paraquat dichloride at concentrations ranging from 10"2 to 10"9 M.
Diethylnitrosamine (DEN) was used as a positive control. This assay
was repeated once using hepatocytes from another rat. This study
satisfies Guideline requirements for genetic effects classified as Other
Genotoxic Effects. (MRID 00152693)
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Technical grade paraquat dichloride (cation content: 33%) was
negative for unscheduled DNA synthesis in rat hepatocytes exposed in
vivo. Suspensions of hepatocytes were prepared from male Alderley
Park SPF albino rats dosed by gavage with paraquat dichloride, water
(controls) or 6BT (6-dimethylaminophenylazo-benzthiazole; positive
control). The single doses of paraquat dichloride used were 0, 45, 75 or
120 mg/kg and the rats were sacrificed at 4 and 12 hours after dosing.
Two separate experiments were performed for each time point. The
selection of doses was governed by the need to evaluate paraquat at
adequate concentrations and that these doses should not induce toxicity
in the hepatocytes. No increase in unscheduled DNA synthesis was
observed at any dose of paraquat dichloride at either time point when
compared with concurrent negative controls, but positive results were
obtained with 6BT. Although hepatocytes from rats in the 120 mg/kg
group showed marked signs of toxicity, sufficient cells of normal
morphology were available to be examined for unscheduled DNA
synthesis. This study satisfies Guideline requirements for genetic
effects classified as Other Genotoxic Effects. (MRID 40202404)
h.
Metabolism
Paraquat was not metabolized by rats. After oral administration
(gastric intubation) of single doses of paraquat dichloride or
dimethylsulfate to Wistar strain male and female rats, most of the
administered radioactivity (69-96%) was excreted in feces as unchanged
paraquat. After subcutaneous injection of these compounds,
unchanged paraquat appeared mostly in urine (73-96% of the
administered radioactivity). Paraquat used in this study (radiochemical
purity: 99-100%) was labeled with 14-C in the methyl groups. The
doses used for gastric intubation ranged from 0.5 to 50 mg/kg and for
subcutaneous injection, from 12.5 to 24 mg/kg. Most of the
radioactivity was detected in feces within 2-3 days after dosing and in
urine, within 1 day after dosing.
Following oral administration of paraquat, up to 30% of the dose
appeared in feces in a degraded form. This was due to the microbial
degradation of paraquat in the gut: That microbial degradation of
paraquat occurred hi feces was shown in an in vitro experiment in which
fecal homogenates were incubated with added paraquat for 24 hours. In
that experiment, 40-50% of paraquat was destroyed. However, a similar
experiment with sterilized fecal homogenates produced only minor loss
(trace amounts) of added paraquat. (MRID 00055107)
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Paraquat was poorly absorbed after oral administration to rats,
dogs and mice. Once absorbed, paraquat was rapidly distributed to
most tissues but especially to lungs and kidneys. Tissues other than
lungs did not retain paraquat. (MRID 00138637, 00132474 and
40202403)
i. Neurotoxicity
Considering the chemical nature of paraquat and the fact that it
has not been shown to inhibit cholinesterase activities, does not produce
cholinergic-like toxic signs and does not affect morphology of the
central and peripheral nervous systems, the following studies are not
required: acute delayed neurotoxicity study in the hen (81-7); acute
(81-8 SS) and subchronic (82-5b or 82-7) neurotoxicity screening
battery studies in the rat; and developmental neurotoxicity study in the
rat (83-6). There is currently no evidence to suggest the need for these
studies.
j. Dermal Absorption
In a dermal absorption study with healthy adult male volunteers,
0.3% of the applied 14C-paraquat dichloride was absorbed through the
intact skin (forearms, and back of the hands and lower legs) during the
24-hour exposure period. (MRID 00153439).
k. Poisoning Incidents
From 1985 through 1994, there were 17 paraquat-related deaths
reported to Poison Control Center's national database from oral
ingestion. Most of the fatal oral ingestions (13 out of 17) have been
related to suicidal incidents. Of the four remaining cases, two were
unknown as to intent and two were accidental ingestions. These two
accidental ingestions occurred when paraquat end-use products were
formulated into a brown liquid which could have been mistaken for a
cola-type of soft drink (prior to 1988). However, since 1988 the
manufacturer has added an emetic (a substance that induces vomiting), a
stenching agent and changed the color (to blue), to try and prevent the
accidental and intentional ingestions from occuring. U.S. Poison
Control Center data, show a decline of almost 50 percent when
comparing the proportion of all pesticide exposures due to paraquat
ingestion for the four years pre- and post 1988.
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Dermal exposure to paraquat usually results in minor skin or eye
irritation. Rarely, with heavier exposures resulting from misuse, more
serious effects may occur such as blistered or ulcerated skin, loss of
fingernails, skin burns, ulcers of the mouth, nosebleeds, and protracted
or even permanent blindness. These more serious effects typically
result when protective clothing is not worn, skin has abrasions or open
cuts, and/or when extensive exposure is allowed to persist without
washing. The label currently warns against these hazards. Heavy,
prolonged dermal exposure, as from a leaking knapsack type of sprayer,
can result in severe poisoning and, rarely, even death. Six such deaths
have been reported outside of the United States when workers failed to
follow label requirements for proper hygiene.
I. Toxicological Endpoints of Concern Identified for Use in
Risk Assessment
Reference Dose fRfD)
On July 20,1995, the Agency's Reference Dose (RfD)/Peer
Review Committee verified the reference dose (RfD) for paraquat which
was last revised on February 1, 1991. The Committee recommended
that the already established RfD, 0.0045 mg/kg/day (expressed as
paraquat cation), be retained. This value was based on the systemic
NOEL of 15 ppm (0.45 mg/kg/day) from the 1-year dog feeding study
(MRID 00132474) and the uncertainty factor (UF) of 100. Chronic
pneumonitis was observed at the next dose of paraquat tested, 30 ppm
(0.93 mg/kg/day), expressed as paraquat cation. The WHO RfD (ADI),
which was last reviewed in 1986, is 0.0040 mg/kg/day, expressed as
paraquat cation.
The following endpoints were determined by the Agency's
Toxicology Endpoint Selection Committee (TESC) on July 25, 1995:
Acute Dietary (1 day")
An acute dietary (1 day) risk assessment is not required. No data
are available that suggest a need for an acute dietary endpoint.
An examination of the data did not provide any toxicological
endpoints that could have resulted from a single acute dietary exposure
when paraquat is used as labeled. In addition, there are many tolerances
for paraquat on raw agricultural commodities (RAG) and virtually all of
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them are at the detection limit. Therefore, the TESC felt that there
would not be any acute dietary problems or concerns with paraquat.
Short Term Occupational Exposure (1-7 days)
The Toxicology Endpoint Selection/Peer Review Committee
indicated inhalation endpoints should be used for risk assessment only
in cases in which the spray particles are of a respirable size. This
endpoint was based on the NOEL and LOEL for subchrpnic (3 weeks)
inhalation toxicity, for both sexes, of 0.01 ug/L and 0.10 ug/L,
respectively, expressed as paraquat cation. This endpoint will not be
used for risk assessment unless the particle size is small enough to be
respirable (such as aerosol spray). (MRID 00113718)
For all other use scenarios (such as agricultural applications), a
"dermal endpoint" is used: NOEL of 3 mg/kg/day, expressed as
paraquat cation, based on maternal and developmental toxicity effects:
unscheduled deaths, thin and hunched appearance, decreased body
weight gain, and histological changes in the lungs and kidneys of the
nonsurvivors. Exposure by the dermal route, obtained by extrapolating
data (NOEL) from a combination of two rat developmental toxicity
studies and correcting for dermal absorption (0.3%), is appropriate for
short term occupational and residential exposure. (MRIDs 00113714,
43964701 and 00153439).
Intermediate Term Occupational (1 week to several months)
The endpoint used is the same as for the Short Term
Occupational or Residential Exposure (above).
Chronic Occupational Exposure (Longer Than Several Months)
The endpoint and dose for use in risk assessment: 0.45
mg/kg/day, expressed as paraquat cation (NOEL for systemic toxicity,
based on the severity and extent of chronic pneumonitis in both sexes),
in the one-year dog feeding study. (Guideline No.: 83-lb, MRID:
00132474)
This risk assessment is not required as there are no chronic
occupational nor residential exposure scenarios for the use of paraquat.
Cancer Classification and Basis:
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The Agency has classified paraquat as a Group E carcinogen
(evidence of non-carcinogenicity for humans), based on a lack of
evidence of carcinogenicity in acceptable studies with two animal
species, rat (Guidelines 83-la/83-2a; MRIDs 00138637, 00153223,
40202401, 40202402, 41317401, 40218001) and mouse (Guidelines 83-
2b; MRIDs 00087924, 40202403), by the Toxicology Branch Peer
Review Committee (now Carcinogenicity Peer Review Committee) on
June 15, 1988, and (again) on March 15, 1989.
2. Exposure Assessment
a. Registered Uses
Paraquat dichloride is currently registered for the control of
broadleaf weeds and grass in agricultural and non-agricultural areas. It
is used as a preplant or preemergence herbicide on vegetables, grains,
cotton, grasses, sugar cane, peanuts, potatoes, and on areas for tree
plantation establishment. Paraquat is applied as a directed spray
postemergence herbicide around fruit crops, vegetables, trees, vines,
grains, soybeans, and sugar cane. It is used for dormant season
applications on clover and other legumes, and for chemical fallow. It is
also used as a desiccant or harvest aid on cotton, dry beans, soybeans,
potatoes, sunflowers, and sugar cane. It is use as a post harvest
desiccant on staked tomatoes, and on pine trees to induce resin soaking.
Paraquat dichloride is applied by aerial, groundboom, backpack
sprayer, and low pressure handwand.
A soluble concentrate/liquid (SC/L) is the sole paraquat
formulation type registered for all uses. This formulation may be
applied to crops pre-plant, at planting, pre-emergence (broadcast or
band), post-emergence (broadcast, band, split, directed, or spot), post-
harvest (as a pre-harvest desiccant or harvest aid), and for suckering and
stripping of hops.
i. Agricultural
Paraquat dichloride end-use products (EPs) with
food/feed uses registered to Zeneca Ag Products are listed
below.
EPA Reg. No. Acceptance Date
Formulation Class
Product Name
10182-103'
4/4/95
1.51b/galSC/L
Gramoxoneฎ Super Herbicide
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EPA Reg. No.
10182-111 b
10182-120
10182-280 **
10182-372
Acceptance Date
4/4/95
4/4/95
4/4/95
4/4/95
Formulation Class
2 Ib/gal SC/L c
29.42% SC/L c
2.5 Ib/gal SC/L
3 Ib/gal SC/L c
Product Name
Cycloneฎ Herbicide
Surefireฎ Herbicide
Gramoxoneฎ Extra Herbicide
Cycloneฎ Concentrate Herbicide
Including SLN Nos. LA870004, LA870005, OHS80002, PA870002, SC820011, and TN940007.
Including SLN Nos. AR820020, NC820010, NM940003, OK940004, SC820024, TX810032, and TX940011.
The 2 and 3 Ib/gal SC/L (EPA Reg. Nos. 10182-111 and 10182-372) and the 29.42% SC/L (EPA Reg. No 10182-120) formulations are
coded by REFs as emulsifiable concentrate (EC) formulations. However, these products were previously identified as SC/L formulations
in the Registration Standard Update.
Including SLN Nos. AL940005, AR950002, CA910021, CA910022, CA910023, CA910024, CA910031, CA910036, CA920006,
CT900001, DE940002, FL900009, FL910004, FL910006, GA940006, HI910001, HI910010, HI920008, ID920010, ID920011, ID930006,
LA940007, MI910009, MN900004, MT940005, NH900001, NH920001, NJ900005, NV910002, NV910003, OH910001, OR910023,
OR910024, OR930009, OR930019, PA900001, SD940005, TN940008, VA930006, VA940012, WA910044, WA910048, WA930014
WA940037, WA950007, and WI900004.
The 2.5 Ib/gal SC/L formulation (SLN No. MN940006) was unavailable for review; the registration jacket did not contain a label.
ii. Non-agricultural
The non-agricultural uses of paraquat are for nonselective
weed control on conservation reserves and non-crop areas such
as public airports, storage yards and electric transformer stations.
One formulation of paraquat dichloride, ICI Spot Weed
and Grass Control (EPA Reg. No. 10182-114), was intended for
homeowner use and was packaged as a ready-to-use pressurized
spray (aerosol) containing 0.276 percent active ingredient. It
was labelled to control weeds and grasses around walks,
driveways, trees, shrubs, and flower beds. However, this
product has never been sold in the U.S. even though it was
registered and has been voluntarily cancelled at the request of
the registrant because of unacceptable risk to the applicator
identified through this reregistration process.
b. Dietary Exposure
The Residue Chemistry data base for paraquat is substantially
complete. The registrant is required to submit data for a few
outstanding data requirements. Sufficient data are available to reassess
the adequacy of the majority of the established tolerances for paraquat
as listed in the relevant sections of 40 CFR. The Agency is requiring
that the tolerance for residues in or on several of the crops be changed,
as detailed in section IV of this document, Tolerance Reassessment
Summary Table.
GLN 171-4 fa'): Plant Metabolism
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For purposes of reregistration and risk assessment, the
qualitative nature of the residue in plants is adequately understood based
on studies depicting the metabolism of paraquat in carrots and lettuce
following pre-emergence treatment and in potatoes and soybeans
following desiccant treatment. The residue of concern in plants is the
parent, paraquat; the current tolerance expression for plant commodities,
as defined in 40 CFR ง180.205(a) and (b), 185.4700, and 186.4700, is
adequate.
In plant metabolism studies reflecting pre-emergence treatment,
the total radioactive residues (TRR) were 0.0048 ppm in carrot root and
0.0034 ppm in lettuce leaf samples following a single pre-emergence
application at ~ 13x the maximum rate of 1 Ib cation/A. These data
suggest that radioactive residues of paraquat are not readily taken up
from the soil in significant quantities by these crop commodities
following this mode of treatment. No further residue characterization
and identification was conducted on these samples because of the low
magnitude of radioactivity obtained.
In plant metabolism studies reflecting desiccant treatment, the
total radioactive residues were 0.075 and 0.087 ppm in potatoes, 0.652
and 0.841 ppm in soybeans, and 506.3 and 768.5 ppm in soybean
foliage following a single foliar desiccant application at ~6x the
maximum seasonal rate of 1.25 Ib cation/A for potatoes and 29x the
maximum single application rate of 0.25 Ib cation/A for soybeans).
Paraquat cation was the major I4C-residue identified, and accounted for
~91% of the total radioactivity hi potatoes, ~84% of the total
radioactivity in soybeans, and virtually all of the total radioactivity in
soybean foliage. Other minor metabolites found in soybean foliage
were QINA (quaternary iso-nicotinic acid), a photodegradant and
monoquat (l-methyl-4,4'-bipyridinium ion), each at 0.3% of TRR.
GLN 171-4 (fr): Animal Metabolism
For purposes of reregistration and risk assessment, the
qualitative nature of the residue in animals is adequately understood
based on the combined results of studies conducted with ruminants
(goats and cows), swine, and poultry. The residue of concern in eggs,
milk, and poultry and livestock tissues is the parent, paraquat; the
current tolerance expression for animal commodities, as defined in 40
CFR ง180.205(a), is adequate.
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In a ruminant metabolism study, a lactating goat was dosed with
ring-labeled [I4C]paraquat dichloride at 103 ppm in the diet for seven
days. The total radioactive residue, expressed as ppm paraquat, was
0.02-0.03 ppm in fat (peritoneal and subcutaneous), 0.08-0.12 ppm in
muscles (fore- and hind-quarter), 0.56 ppm in liver, and 0,74 ppm in
kidney. The maximum total radioactivity in milk increased daily to a
maximum of 0.0092 ppm paraquat ion equivalents four hours before
slaughter; 75.7% of the TRR of this sample was found to be paraquat.
In edible tissues, paraquat accounted for the majority of the identified
residues including -49-120% of TRR in fat, -90-100% of TRR in
muscle, -48% of TRR in liver, and -95% of TRR in kidney. Other
metabolites that were identified in tissues were the monopyridone of
paraquat (l,2-dihydro-l,r-dimethyl-4,4'-bipyridinium ion) which
accounted for 3.2% of TRR in liver and monoquat which accounted for
3.4% of TRR in liver and 6.5% of TRR in peritoneal fat.
A pig metabolism study reflecting use of ring-labeled
[14C]paraquat and a feeding level of 2.44 ppm is also available. Total
radioactive residues were 0.20 ppm paraquat equivalents in liver, 0.38
ppm in kidney, 0.05 ppm in muscle, and 0.01 ppm in fat Paraquat was
found to comprise -70% of TRR in liver, 101% of TRR in kidney, 95%
of TRR in muscle, and 106% of TRR in fat. Liver tissue, the only tissue
analyzed for residues other then paraquat, was found to contain
monoquat at -4% of TRR.
In a poultry metabolism study, laying hens were dosed with ring-
labeled [14C]paraquat at 30 ppm in the diet for ten consecutive days.
Radioactive residues were found in all examined tissues (including
liver, abdominal and subcutaneous fat, and leg and breast muscle).
Paraquat was the major residue (-80-98% of TRR) identified in all
poultry tissues; monoquat was a minor metabolite (-4% of TRR each)
in liver and kidney. Virtually all of the radioactivity in the yolk was
identified as paraquat; no analysis of albumen was reported.
GLN 171-4 (c) and (d): Residue Analytical Methods-Plants and
Animals
The requirements for residue analytical methods are partially
fulfilled for purposes of reregistration, pending submission of
supporting raw data for the radiovalidation study of the method for plant
commodities. Acceptable methods are available for enforcement and
data collection purposes both in plant and animal commodities.
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Methods for determination of residues in/on plant commodities:
The Pesticide Analytical Manual (PAM Vol. II) lists a
spectrophotometric method, designated as Method I (LOD = 0.01-0.06
ppm), as available for the enforcement of tolerances in plant
commodities. Several modifications of Method I have been developed
for analysis of specific crops, and these modified methods were used for
data collection. Samples from field trial and processing studies,
submitted to fulfill reregistration requirements, were analyzed for
residues of paraquat using Methods IB, 2B, 3A, and 3B, and Methods
RM-8, RM-8-9, RM-8-10, and RM-8-11. Method I along with its
modifications all include extraction in acid solution, adsorption of
residues on a cation-exchange resin, elution with saturated ammonium
chloride, reduction with sodium dithionite to give a blue-colored
solution of free radical, and detection by spectrometry. The registrant
provided adequate method validation data to verify the suitability of
Methods IB, 2B, 3A, and 3B for data collection.
In conjunction with recently submitted plant metabolism studies,
the registrant has provided radiovalidation data for Method IB using
radiolabeled samples. The Agency tentatively concluded that Method
IB adequately recovers paraquat cation residues from samples of
potatoes and soybeans treated with [14C]paraquat. The registrant has
recently submitted representative spectra and other supporting raw data
from the radiovalidation study; upon the Agency's review of this
additional information, the requirements for residue analytical methods
for plant commodities will be considered fulfilled for reregistration
purposes.
Methods for determination of residues in animal commodities:
The Pesticide Analytical Manual (PAM Vol. II) lists a
spectrophotometric method, designated as Method la (LOD = 0.005
ppm), as available for the enforcement of tolerances in animal
commodities. The registrant has submitted descriptions and adequate
independent laboratory validation data for a high-performance liquid-
chromatography method (HPLC; designated as Method 4B) to
determine paraquat residues in animal tissues and eggs. The method has
been validated by the Agency's Beltsville laboratory, and the registrant
is required to make minor changes in the method write-up.
Multiresidue Methods: The FDA PESTDATA database (dated
1/94) does not have an entry for paraquat. The existing FDA
multiresidue methods are not likely to recover paraquat residues owing
to its ionic nature.
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GLN 171-4 (e): Storage Stability
Provided that the final results of storage stability studies for
cabbage, carrots, and milk are acceptable, the requirements for storage
stability data will be considered fulfilled for reregistration purposes;
these requested studies have recently been submitted to the Agency
(MRID#'s 43954003 and 43954004) and will be reviewed in the near
future. Although the storage stability of paraquat has not been
investigated in any oilseed or nut and the storage stability data on
processed commodities are rather limited, no additional storage stability
data are required for reregistration purposes provided the recently
submitted stability study data are adequate; in practically all examined
cases, paraquat residues were found to be stable at the maximum storage
intervals tested. The available data for corn grain may be translated to
oilseeds.
GLN 171-4 (10: Magnitude of the Residue in Plants
Pending required label amendments and/or revised tolerances,
the reregistration requirements for magnitude of the residue in/on plants
are fulfilled for the following commodities: acerola; almond hulls;
apples; apricots; asparagus; avocados; bananas; barley grain, forage,
and straw; beans, dry and succulent; beans, forage, hay, and straw;
broccoli; cabbage; cacao beans; carrots; cassava; cauliflower; cherries;
Chinese cabbage; citrus fruits group; coffee beans; collards; com, field,
grain; corn, field, forage and fodder; corn, pop, grain; corn, pop, fodder;
corn, sweet (K + CWHR); corn, sweet, forage and fodder; cottonseed;
cucurbit vegetables group; figs; fruiting vegetables (except cucurbits)
group; grass, rangeland, forage; grass, pasture, forage; grass, pasture,
hay; guar; guava; hops, dried; kiwifruit; lentils; lentils, forage; lettuce;
mint tops; nectarines; non-grass animal feeds group, forage; non-grass
animal feeds group, hay; olives; onions, dry bulb and green; papayas;
passion fruit; peanuts; peanuts, hay and hulls; pears; peas, pigeon; peas,
succulent; peas, hay and vines; pineapples; peaches; pistachios; plums;
potatoes; rhubarb; rice, grain and straw; safflower, seed; small fruits and
berries group; sorghum, grain; sorghum, forage and fodder; soybeans;
soybeans, forage, and hay; strawberries; sugar beets, roots and tops;
sugarcane; sunflower seeds; taniers; taro corms; tree nuts group; turnips,
roots and tops; tyfon; wheat grain, forage, and straw; and yams.
Adequate field trial data depicting residues of paraquat following.
treatments according to the maximum registered use patterns have been
submitted for the commodities listed above or have been translated
where appropriate.
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Table I (OPPTS 860.1000) recognizes barley hay, cotton gin
byproducts (formerly called gin trash), and wheat hay as raw
agricultural commodities (RACs). Residue data are now required for
these RACs, and appropriate tolerances should be proposed once
acceptable data have been submitted and evaluated. The. required data
for wheat hay may be translated to barley hay.
Table I of OPPTS 860.1000 no longer recognizes cotton forage,
popcorn forage, pineapple forage, sorghum hay, safflower forage,
sorghum silage, and sugarcane forage as RACs. Therefore, no residue
data are required for these commodities and tolerances need not be
established. In addition, Table I no longer recognizes fresh hops, hop
vines, lentil hay, and peanut vines as RACS; therefore, the established
tolerances for these commodities will be revoked.
The registrant has expressed an intention to petition the Agency
for the revocation of the established tolerances for oat grain and rye
grain since the registrant claims there are no longer any registered uses
of paraquat on these commodities. Therefore, the tolerances for oat
grain and rye grain will be revoked.
No residue data or tolerance currently exists for taro foliage.
The registrant must submit field residue data and a tolerance proposal
for residues of paraquat in/on taro foliage.
Additional data are required for soybean aspirated grain dust.
The Agency has recently revised its policy on aspirated grain dust and
determined that it should be considered a RAC [see memo on
"Aspirated Grain Fractions (Grain Dust): A Tolerance Perspective", E.
Saito and E. Zager, 6/7/94]. The Agency also determined that a
tolerance for aspirated gram fractions for a pesticide should be
established based on the use of the pesticide on corn, wheat, sorghum,
and soybeans; paraquat is presently registered for use on these crops. A
soybean grain dust study has been submitted and was deemed
unacceptable because the data from the study could not be used reliably
to calculate the potential for concentration of paraquat residues in the
subject commodity. The Agency believes that based on paraquat
registered uses on soybeans, which include post-emergence directed
spray and use as a harvest aid, a potential exists for paraquat residues to
concentrate in/on soybean grain dust, and the registrant has committed
to conduct a new soybean aspirated grain dust study.
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No grain dust data are required for wheat and sorghum because
finite residues are not expected on the grain dust of these crops since
paraquat is registered for use only during the vegetative (and not the
reproductive) stages. With respect to com, however, the Agency has
recently approved a SLN registration (TN940007) for use on corn as a
harvest aid (PHI of 7 days). To support this use, the Agency will
require additional field trials with corn as well as an aspirated grain
fraction study.
GLN 171-4 (1): Magnitude of the Residue in Processed Food/Feed
The reregistration requirements for magnitude of the residue in
processed food/feed commodities are fulfilled for: apples; barley; cacao
beans; citrus; coffee; corn, field; cottonseed; figs; hops; mint; olives;
peanuts; pineapples; plums; potatoes; rice; safflower; sorghum;
soybeans; sugar beets; sugarcane; sunflower; tomatoes; and wheat.
Data depicting the magnitude of the residue in the processed
commodities of grapes remain outstanding. The registrant must submit
data depicting the potential for concentration of paraquat residues in the
processed commodities of grapes bearing detectable weathered residues.
Residue data showed that residues concentrate in corn flour, soybean
hulls, pineapple processing residue, and sugarcane molasses. Tolerances
have been proposed accordingly for these commodities (see section IV,
Tolerance Summary Table). No processing data are required for
processed commodities of oats or rye since the registrant does not wish
to support the RAC tolerances for oat grain and there are presently no
registered uses of paraquat on rye grain.
GLN 171-4
is
Magnitude of the Residue in Meat. Milk. Poultr, and
There are no registered direct animal treatments for paraquat on
cattle, goats, hogs, horses, sheep, or poultry. Based on acceptable
animal metabolism studies and magnitude of the residue in animal
studies, uses of paraquat are classified as Category (1) of 40 CFR
ง180.6(a); finite residues will be incurred in foods from feed use of the
RAC including its byproducts. The residue of concern in eggs, milk,
and poultry and livestock tissues has been determined to be the parent,
paraquat; the current tolerance expression for animal commodities, as
defined in 40 CFR ง180.205(a), is adequate.
Magnitude of the residue in milk, fat, meat, and meat byproducts
of ruminants: The maximum expected dietary intake of paraquat
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residues by beef and dairy cattle was previously calculated to be
approximately 11 ppm. Based on tolerance reassessments of many
livestock feed items [including the forage and hay of non-grass animal
feeds (e.g., alfalfa) as well as grass forage], the new dietary burdens for
beef cattle and dairy cattle are recalculated to be 216 ppm and 252 ppm,
respectively.
The Agency has reevaluated the existing magnitude of the
residue data for milk and ruminant tissues and has determined that these
data are considered sufficient for reliable risk and tolerance
assessments: while the 170 ppm feeding rate represents only 0.7x the
maximum theoretical dietary burden, the Agency believes that a new
feeding study is not required since there do not appear to be significant
changes in tissue levels between 25 ppm and 170 ppm dosing levels. In
addition, the cows in the feeding study were dosed at 170 ppm (0.7x)
for 86-95 days. Since 170 ppm represents a concentration very close to
the concentration expected following immediate consumption of a
treated crop (i.e., a 0-day PHI), it is unlikely that a cow would consume
this dietary level for any extended period of time.
Based on the existing magnitude of the residue data for meat and
ruminant tissue, the Agency will recommend the following tolerances
for meat, fat, kidney and liver:
Muscle:
Fat:
Kidney:
Liver:
0.05 ppm
0.05 ppm
0.5 ppm
0.05 ppm
The Agency does not believe that detectable residues will result
in milk (normally considered a 180.6(a)(3) situation), but will
recommend retention of the present 0.01 ppm tolerance in the interest of
harmonization with the CODEX MRL of 0.01 ppm.
Magnitude of the residue in eggs, fat, meat, and meat byproducts
of poultry: The maximum expected dietary intake of paraquat residues
by laying hens was previously calculated to be 1.4 ppm. Based on
tolerance reassessments of many poultry feed items, the new dietary
burden for poultry is calculated to be 1.1 ppm.
The Agency has reevaluated the existing magnitude of the
residue data in eggs and poultry tissues in conjunction with the
reassessments of tolerances for all poultry feed commodities. The
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available poultry feeding data indicate that non-egg poultry
commodities are a 180.6(a)(3) situation and no tolerances need be
established. In the interest of harmonization with CODEX, the Agency
will recommend maintaining the current 0.01 ppm tolerance on eggs.
GLNs 165-1 and 165-2: Confined/Field Rotational Crops
An acceptable confined rotational crop study has been submitted.
The study indicated that residues of paraquat do not accumulate in
rotated crops planted up to 120 days following treatment; therefore, no
plantback restrictions or field rotational crop studies are required.
c. Occupational and Residential
Handler Exposures & Assumptions
The Agency has determined that there is potential exposure to
mixers, loaders, applicators, and other handlers during usual use-
patterns associated with paraquat dichloride. The Agency has identified
exposures to handlers during the agricultural and non-agricultural uses
of paraquat dichloride, including mixing and loading, and during
application by ground and aerial equipment, particularly backpack
applicators. Mixer/loader/applicator (M/L/A) exposure data for
paraquat dichloride were required in the December 1991 Data Call-In
(DCI) and in response to the Worker Protection Standard. These data
are discussed below.
Based on the use patterns, several major occupational exposure
scenarios were identified for paraquat dichloride: (1) mixing/loading
liquid formulations for ground boom application; (2) mixing/loading
liquid formulations for aerial application; (3) applying as a spray with a
tractor-drawn ground boom; (4) applying as a spray with aerial
equipment; (5) mixing/loading liquid formulations for backpack
spraying; (6) applying as a spray with a backpack sprayer; (7) flagging
for aerial spray applications; (8) mixing, loading, and applying the
liquid formulation for spot treatment with a low pressure sprayer; (9)
mixing, loading, and applying the liquid formulation for spot treatment
with a backpack sprayer; and (10) mixing, loading, and applying the
liquid formulation for resin soaking uses with a low pressure sprayer.
The following chemical-specific mixer/loader/applicator study
was submitted by the registrant:
45
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MRID Number: 436442-02. 1995. D. Meier. Paraquat:
Worker Exposure During Mixing, Loading, and Application of
GRAMOXONEฎ EXTRA to Pecans Using Vehicle-Mounted
Ground Boom Equipment.
This worker biomonitoring study was performed to support label
revisions related to personal protective equipment required for mixers,
loaders, and applicators. Paraquat formulated as GRAMOXONEฎ
EXTRA herbicide in water was applied at a maximum application rate
of 0.94 Ib cation/Acre by ground boom spray to pecan orchards in
southwestern Georgia and southeastern Alabama in September, 1994.
Urinary excretion of paraquat was measured as the indicator of exposure
to workers mixing, loading, and applying the herbicide. A total of 17
combined mixer/loader/applicator replicates were monitored. The
Agency has reviewed this study and considers it acceptable since it
adequately meets Subdivision U Guidelines of the Pesticide Assessment
Guidelines.
Application of paraquat was conducted on fifteen separate pecan
farms using ground boom spray equipment mounted on open-cab
tractors. Three pints Gramoxoneฎ EXTRA herbicide were mixed with
surfactant and water to 13 to 42 gallons/acre spray mixture. Workers
either poured the formulated product directly into the spray tank or
measured it into a calibrated container before transferring it to the spray
tank.
Although the study sponsor requested that the workers comply
with label requirements for personal protective equipment (PPE), they
did not interfere with the individual subject's typical practices. As a
result, a wide variety of PPE was employed. Of a total of 17
individuals, only eight wore gloves while mixing. The remaining nine
wore only normal work clothing. Three wore face/eye protection, and
wore an apron in addition to protective gloves. Two workers wore
Tyvek suits during application. The time spent mixing and loading
ranged from 14 to 104 minutes, and the total time of exposure from 230
to 660 minutes. Activities relevant to exposure were reported. The total
amount of paraquat handled varied from orchard to orchard, with a
range of 9.5 to 69 pounds of active ingredient.
The Limit of Quantification (LOQ) was stated to be 10 ng/ml for
a 1 ml urine sample. The level of detection was given as 5 ng/ml. The
study results showed that six of the 17 urine samples collected
contained detectable paraquat. All were in the Day 1 (application
46
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exposure day) samples. Absorbed paraquat was estimated using a
referenced excretion rate of 59% from a paraquat pharmacokinetics
study in monkeys. The pharmacokinetics of paraquat have been
verified by the Agency.
Of the six workers with detectable paraquat exposure, none wore
protective equipment while handling the formulation. There was no
discernable trend between the amount of pesticide handled and the
exposure incurred.
The available biomonitoring data for uses of paraquat are
summarized in Table A. These data originate from the groundboom
study (MRID 436442-02).
Total daily dose is calculated using the following formula:
Total Daily Dose (mg/kg/day) =
Unit Dose (mg/kg/lb ai) X Appl Rate (Ib cation/acre) X Acres Treated/Day
Margin of Exposure is calculated using the following equation:
MOE = NOEL -e- Total Daily Dose
47
-------
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PHED Vl.l data are used to estimate short- and intermediate-
term exposure, dose, and risk from paraquat for backpack sprayer
mixer/loaders and applicators, for flaggers for aerial spray applications,
for mixers/loaders/applicators for spot treatments using a backpack
sprayer or low pressure wand, and for mixers/loaders/applicators for
resin soaking uses using a low pressure wand. These exposure
scenarios are presented in Tables B and C. Inhalation exposure and
doses were not calculated since spray particles used in applying
paraquat are well beyond the respirable range and paraquat has a very
low vapor pressure. The potential daily dermal dose is calculated using
the following formula:
Potential Daily Dermal Dose (mg/kg/day) =
Dermal Unit Exposure (mg/lb ai) X max. Appl. Rate (Ib cation/amount) X max. area
treated (amount/day) X Dermal Absorption H- Body Weight (kg)
These calculations of daily dose of paraquat received by handlers
are used to assess the risk to those handlers. The dermal Short-Term
and Intermediate-Term MOE was calculated using the following
formula:
Dermal MOE = NOEL (mg/kg/day) * Potential Daily Dermal Dose (mg/kg/day)
49
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Post-Application Exposures & Assumptions
The Agency has determined that there is potential exposure to
persons entering treated sites following: (1) preemergent/early-season
treatments, particularly in crop areas; (2) directed spray treatments,
particularly in orchard or vegetable-crop sites with heavy weed density;
and, (3) desiccant/harvest-aid treatments particularly when performing
harvesting-related tasks, such as removal or compacting (i.e. trampling)
of desiccated foliage and stems on crops such as cotton, dry beans,
potatoes, sunflowers, and sugar cane.
Post-application exposure data were required in the December
1991 DCI and in response to the Worker Protection Standard.
The following post-application study was submitted by the
registrant:
MRID Number - 436182-02. Tak Iwata and Malcolm Findlay,
1994. Worker Exposure During Re-Entry into Paraquat-Treated
Cotton Fields: Biological Monitoring in Georgia in 1994.
This worker biomonitoring study measured urinary excretion of
paraquat as a indicator of exposure to workers reentering the treated
fields for the purpose of scouting. Cotton fields were treated with
STARFIRE, a product normally used by growers as a harvest aid, at a
rate of 0.55 Ib cation/A. Scouting activities started at 4 hours (12
replicates) and 24-hours (13 replicates) post-application. Scouting
activities consisted of walking into the field, handling and cracking a
few bolls, and bending foliage and stems for a total field exposure of 2.5
hours. Complete 24 hour urine samples were collected from each
subject on the reentry exposure day and on the next 5 days.
The study results showed that only one urine sample contained
detectable paraquat. This was from a Day 1 (reentry exposure day)
urine sample from a subject in the 4 hour reentry test group. Based on a
reported urinary level of 6 mg/ml and a sample volume of 400 ml, a
total amount of paraquat excreted was estimated as 0.0024 mg. An
exposure of 0.00004 mg/kg/day was calculated for this subject using a
204 pound body weight and a referenced excretion rate of 59% from a
paraquat pharmacokinetics study in monkeys (see MRID No. 436182-
01). All other (non-detect) data points were treated as containing no (0)
paraquat.
53
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3.
The authors also present an exposure assessment in a separate
submission (MRID No. 436182-01) which contains an estimate of a
Margins of Exposure (MOE). Using a NOEL value of 0.6 mg/kg for a
90 day feeding study in dogs (from the 1987 Registration Standard,
which identifies this level as 0.5 mg/kg/day), a MOE of 15,000 was
derived. Based on this value and the stated "worst case" conditions of
the study, the authors suggest that workers could safely reenter
paraquat-treated fields (cotton as well as other crops) 4 hours after
application (when sprays have dried).
The Agency has confirmed the pharmacokinetic data used in this
study. A single dose of paraquat dichloride administered
subcutaneously to rats was excreted mostly in urine (73-96%) as
unchanged paraquat within 24 hours after dosing. Therefore adequate
time was allowed in this experiment for urine collection.
The Agency considers this study acceptable since the EPA-
approved protocol was followed. After the protocol was approved, the
Agency exempted certified or licensed crop advisors and their
employees from the Worker Protection Standard requirements, except
for obtaining pesticide safety training, based partially on the assumption
that such activities result in low exposures (FR, Vol. 60, No. 85,
5/3/95). In addition, the 2.5 hour duration of exposure may suggest that
this study was not in fact a worst-case scenario relative to other crops
and cultural practices. Therefore, the Agency is requiring reentry
intervals longer than 4 hours which had been previously suggested (see
Risk from Post-Application Exposures for specific Agency
requirements).
Risk Assessment
a. Dietary
Residues
Tolerances for paraquat residues in/on raw agricultural and
animal commodities are published in 40 CFR ง180.205(a) and (b), in
processed food hi 185.4700, and in feed at 186.4700. The available
data support the established tolerances on all but sorghum forage,
ruminant kidney, oats, rye, soybeans and hops. Thus, for the purposes
of this analysis, the tolerances for sorghum forage was reassessed from
O.OSppm to the higher value of 0.1 ppm, while kidney was reassessed
54
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from 0.3 ppm to 0.5 ppm, soybeans from 0.05 ppm to 0.25 ppm, and
hops from 0.2 ppm to 0.5 ppm.
Chronic Dietary Exposure
A DRES (Dietary Risk Evaluation System) chronic exposure
analysis was performed using tolerance level residues and percent crop
treated to estimate the Anticipated Residue Concentration (ARC) for the
general population and 22 population subgroups. Even with rye, oats,
and poultry commodities included, the Reference Dose (RfD) was not
exceeded for any of the 22 population subgroups analyzed.
As there are presently no registered uses of paraquat on rye, it is
recommended that tolerances for this commodity be revoked. It is also
recommended to revoke the tolerance on oats, as the registrant has
indicated that they do not wish to support this use. Additionally, it is
recommended that tolerances for poultry (except for eggs) be revoked.
Further, a tolerance for popcorn (0.05 ppm) was included in this
analysis and should be proposed (See Section IV, Tolerance
Reassessment Summary and Table).
Chronic Dietary Exposure Using Tolerances
Existing tolerances result in a Theoretical Maximum Residue
Contribution (TMRC) which represents 10% of the RfD for the U.S.
general population. The highest subgroup, non-nursing infants (<1 year
old) occupies 31% of the RfD.
Dietary Risk to Paraquat
Subgroup
U.S. Population
Non-Nursing Infants (<1 year old)
Children (1-6 years old)
Exposure (mg/kg/day)
0.000442
0.001398
0.001070
%RfD
10
31
24
b. Occupational and Residential
Risk From Handler Exposures
Based on biological monitoring data, the margins of exposure
(MOEs) are acceptable (greater than 100) for: (1) mixing/loading to
support ground applications; (2) mixing/loading to support aerial
55
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applications; (3) applying using ground boom equipment; and (4)
applying using aerial equipment (ground boom data were used as a
surrogate for aerial). Surrogate exposure data from PHED indicate that:
(1) mixing/loading liquid formulations to support several applicators
using backpack sprayers; (2) flagging; (3) mixing/loading/applying for
spot treatments using low-pressure sprayers or backpack sprayers are
acceptable; and (4) with the addition of gloves mixing/loading/applying
for resin soaking uses using low-pressure sprayers (MOEs greater than
100).
Based on exposure data from PHED, the MOE for backpack
applicators (non-spot treatment) is unacceptable (MOE less than 100)
when applicators are wearing long pants and long sleeved-shirt, and
chemical-resistant gloves. The Agency is concerned about the
practicality of adding another layer of PPE (woven material), due
primarily to heat stress considerations and the "wicking" affect of
multiple layers. As a risk mitigation measure, all paraquat labels could
be modified to specify that backpack applications for spot treaments be
made at application rates no higher than 0.0195 Ib cation/gal (or 0.23%
cation wt/wt spray solutions).
Risk From Post-Application Exposures
Based on the postapplication biological monitoring study The
Agency has determined that a 12-hour restricted-entry interval is
adequate for the uses of paraquat for preemergent or early-season weed
control. In these use-situations, the paraquat is directed at the soil and
weeds (if present) that are generally less than six inches tall and the
workers' degree and duration of contact with treated surfaces is likely to
be similar to or less than that for the scouts in the biological monitoring
study.
Based on the postapplication biological monitoring study, The
Agency also has determined that a 12-hour restricted-entry interval is
adequate for the uses of paraquat for weed control in orchard and
vegetable crops where the spray is directed solely at the weeds (not
broadcast over the entire crop area). In these directed-spray use-
situations where the paraquat is directed at the weeds, entering workers'
degree and duration of contact with treated surfaces are likely to be
similar to or less than that for the scouts in the biological monitoring
study.
56
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For desiccation and harvest aid applications of paraquat, The
Agency is establishing a 24-hour restricted-entry interval (REI). The
Agency believes that such uses may result in exposures to workers of
greater degree and duration than that for the scouts in the biological
monitoring study, particularly when the workers are performing
harvesting-related tasks, such as removal or compacting (i.e. trampling)
of desiccated foliage and stems on crops such as cotton, dry beans,
potatoes, sunflowers, and sugar cane. It is well documented that
paraquat is rendered biologically inactive upon contact with the soil.
However less is known about its residues on leaves. After 21 days, 66%
of paraquat is lost from plant surfaces. The Agency does not have any
foliar dissipation curves for paraquat to better quantify post-applicator
exposure. Personal protective equipment is required for workers who
enter the treated area before the REI has expired.
The 12 and 24-hour post-application entry restrictions for
paraquat dichloride do not apply to uses outside the scope of the Worker
Protection Standard (WPS) for Agricultural Chemicals. The predicted
frequency, duration, and degree of exposure by such uses do not
warrant the same risk mitigation measures required for users covered by
the WPS who are engaged in agriculture for commercial or research
purposes. However, the Agency is concerned about exposures
immediately following applications while the sprays are still wet.
Additional Occupational/Residential Exposure Studies Handler
Studies
None are necessary.
Post-Application Studies
If the registrant believes that a restricted-entry interval of less
than 24 hours is appropriate for the desiccation/harvest-aid uses of
paraquat, an additional study is required. Requirements for post-
application exposure studies are addressed by Subdivision K of the
Pesticide Assessment Guidelines. The required data include: Guideline
132-1 (a): Foliar Residue Dissipation.
4. Food Quality Protection Act Considerations
The Food Quality Protection Act of 1996 (FQPA) amended the FFDCA
by setting a new safety standard for the establishment of tolerances. In
determining whether a tolerance meets the new safety standard, section
57
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408(b)(2)(C) directs EPA to consider information concerning the susceptibility
of infants and children to pesticide residues in food, and available information
concerning aggregate exposure to infants and children of such residues, as well
as the potential for cumulative effects from pesticide residues and other
substances that have a common mechanism of toxicity.
The FQPA amendments to section 408(b)(2)(C) also direct the Agency,
in the case of threshold effects, to add an additional 10-fold margin of safety
for the protection of infants and children unless the Agency concludes, based
upon reliable data, that a different safety margin will be safe for infants and
children.
Section 408(b)(2)(D) establishes factors that the Agency must consider
in determining whether the safety standard is met in deciding to issue or
reassess tolerances. These factors include the consideration of available
information on the aggregate exposures to the pesticide from dietary sources
including drinking water as well as non-occupational exposures such as those
derived from pesticides used in and around the home. The Agency must also
consider available information concerning the potential cumulative effects of
the pesticide for which a tolerance is being sought as well as other substances
that have a common mechanism of toxicity for the general population and
major subgroups of the population.
Because paraquat has food uses, specific consideration of the risks to
infants and children, as well as aggregate exposures and potential cumulative
effects is warranted.
a. Potential Risks to Infants and Children
In determining whether a safety factor different than the
additional 10-fold factor is or is not appropriate for assessing risks to
infants and children, EPA considers all reliable data and makes a
decision using a weight of evidence approach taking into account the
completeness and adequacy of the toxicity data base, the nature of the
effects observed in pre and post-natal studies, and other information
such as epidemiological data.
For the purpose of assessing the pre- and post-natal toxicity of
paraquat, EPA has evaluated four developmental (of which two were
used to evaluate developmental and maternal toxicity) and one
reproduction study. Based on current data requirements, these three
studies constitute a complete data base for evaluating pre and post natal
effects for food use chemicals when considered along with other
58
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required toxicity studies. However, as EPA fully implements the
requirements of FQPA, additional data related to the special sensitivity
of young organisms may be required.
Developmental and Reproductive Effects
The effects observed in the paraquat developmental and
reproduction studies can be summarized as follows:
Four developmental/maternal toxicity studies were evaluated for
paraquat. The following two were used to assess the
developmental/maternal toxicity of paraquat. In the first of the two
studies, no developmental effects were found, and the developmental
NOEL was set at 8 mg/kg/day (HDT), and the maternal NOEL at 8
mg/kg/day (HDT).
In the second of the two studies, maternal toxicity was reported
at the two highest doses and included clinical signs, decreased body
weight gain, deaths of 6 high dose animals versus none in the control
group, respiratory distress in 3 high-dose females, histopathological
findings in the lungs and kidneys of the nonsurvivors. Developmental
effects (delayed ossification in the forelimb and hindlimb digits) were
observed only in the mid-dose and high-dose groups. Based on these
findings, the NOEL and LOEL for maternal toxicity are 1 mg/kg/day
and 5 mg/kg/day, respectively, expressed as paraquat cation. The
NOEL and LOEL for developmental toxicity are also 1 mg/kg/day and 5
mg/kg/day, respectively.
The overall maternal and developmental NOEL for the rat is 3
mg/kg/day (paraquat cation) based on a weight-of-evidence of the
results from two developmental studies in the rat.
In a reproductive study in rats, the NOEL and LOEL for
systemic toxicity are 1.25 mg/kg/day and 3.75 mg/kg/day, respectively.
The NOEL for reproductive toxicity is z 7.5 mg/kg/day (HDT), based
on severe lung damage caused by paraquat (red or purple discoloration,
congestion, edema, fibrosis, hyaline membrane formation, inflammatory
cell infiltration and/or hyperplasia) and incidence of alveolar
histiocytosis. Paraquat, at all levels tested, had no effect on body weight
gain, food consumption and utilization, fertility and length of gestation.
The developmental data for paraquat indicate developmental
effects occurred at doses that were the same as or higher than doses
59
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which cause maternal toxicity. The Agency would generally be
concerned when developmental/reproductive effects are seen at doses
lower than those which cause maternal effects. The developmental
studies hi conjunction with the reproduction study do not indicate any
additional sensitivity of young organisms to paraquat. Based on current
toxicological data requirements, the data base, relative to pre- and post-
natal toxicity, is complete.
Uncertainty Factor
Based on reliable data as outlined above, the Agency concludes
that an additional uncertainty factor is not warranted for the paraquat
chronic risk assessment, nor is the use of an additional uncertainty
factor indicated for estimating risk from acute exposures detailed below.
b. Aggregate Exposure/Risk
In examining aggregate exposure, FQPA directs EPA to take
into account available information concerning exposures from the
pesticide residue in food and all other exposures for which there is
reliable information. These other sources of exposure include drinking
water, and non-occupational exposures, e.g., to pesticides used in and
around the home. For estimating acute arid chronic risks the Agency
considers aggregate exposures form the diet and from drinking water.
Exposures from uses in and around the home that may be of short term,
intermediate or other duration may also be aggregated as appropriate for
specific chemicals.
Paraquat has no residential or other non-occupational uses that
might result in exposure to children. In addition, paraquat is not
expected to be a contaminant of groundwater. Paraquat dichloride binds
strongly to soil clay particles and it did not leach from the surface in
terrestrial field dissipation studies. There were, however, detections of
paraquat in drinking water wells from two states cited in the Pesticides
in Ground Water Database(1991X These detections are not considered
to be representative of normal paraquat use. Therefore, paraquat is not
expected to be a groundwater contaminant or concern based on normal
use patterns.
Due to its persistent nature, paraquat could potentially be found
in surface water systems associated with soil particles carried by
erosion, however, paraquat is immobile in most soils, and at very high
application rates (50-1OOOX), there was no desorption of paraquat from
60
-------
soils. Therefore, based on paraquat's normal use patterns and unique
environmental fate characteristics, exposures to paraquat in drinking
water are not expected to be obtained from surface water sources .
Thus, the only exposures considered in acute and chronic risk
assessments are dietary.
Acute Risk
No data are available that suggest an acute dietary endpoint of
concern, therefore an acute dietary risk assessment was not required for
paraquat.
Chronic Risk
Dietary Exposure
A chronic dietary exposure analysis was performed using
tolerance-level residues and percent crop treated information for some
crops resulting in an ARC (Anticipated Residue Concentration) of 10%
of the RfD for the US population, 24 and 31% of the RfD for children
(ages 1-6) and non-nursing infants (<1 yr), respectively.
Tolerances have been established in/on over 80 crops. The
available data support the established tolerances listed in 40 CFR
section 180.205 (a) and (b) in processed food in 185.4700, and in feed
at 186.4700 on all but sugar beet tops, ruminant kidney, oats, rye,
soybeans and hops which need to be amended.
Conclusion Regarding Chronic Aggregate Exposure to Paraquat
The Agency concludes that the aggregate risks to the general
U.S. population, and to the population subgroup of infants and children,
resulting from paraquat uses are not of concern.
c.
Cumulative Effects
In assessing the potential risk from cumulative effects of
paraquat and other chemical substances, the Agency has considered
structural similarities that exist between paraquat and other bipyridylium
compounds such as diquat dibromide. Examination of the toxicology
databases of paraquat and diquat dibromide, indicates that the two
compounds have clearly different target organs. At doses at which
61
-------
paraquat is a highly specific pulmonary toxicant in rats and dogs, diquat
produces cataracts and no significant pulmonary toxicity in the same
species. Although both chemicals presumably can induce tissue
damage via the generation of oxygen free radicals, the two compounds
differ in their tissue distribution pattern. Unlike paraquat, diquat shows
no special affinity for the lung and appears to be taken up by the
transport mechanism that selectively concentrates paraquat in the lung.
Paraquat is accumulated in the lungs and is thus a lung toxicant,
whereas diquat is not accumulated in the lungs and is not a lung
toxicant.
Although paraquat also produced a dose-related incidence of
cataracts in Fisher 344 rats after 103 weeks, a dose-related incidence of
cataracts was not seen in chronic studies with Wistar rats, beagle dogs
or JCL-ICR mice. Thus, paraquat appears to be a weaker cataractogenic
agent when compared to diquat.
Based on the available data, the Agency does not believe that the
toxic effects produced by paraquat would be cumulative with those of
diquat dibromide.
C. Environmental Assessment
The environmental fate and ecological toxicity data bases are complete.
Paraquat dichloride poses a risk to nonendangered and endangered non-target
terrestrial and aquatic plants. Acute risk to terrestrial organisms only exists
immediately after application. Although a chronic risk to birds is not expected as a
result of residues on dietary food items, the Agency is concerned that direct
application of paraquat dichloride to eggs may affect avian reproduction.
1. Ecological Toxicity Data
Sufficient ecological toxicity data exist to assess the risk of paraquat
dichloride to non-target wildlife.
a. Toxicity to Terrestrial Animals
(1) Birds, Acute and Subacute
In order to establish the toxicity of paraquat dichloride to
birds, the following tests are required using the technical grade
material: one avian single-dose oral (LD50) study on one species
(preferably mallard or bobwhite quail); two subacute dietary
62
-------
studies (LC50) on one species of waterfowl (preferably the
mallard duck) and one species of upland game bird (preferably
bobwhite quail). The following two tables summarize the avian
acute oral toxicity findings and the avian subacute dietary
toxicity findings.
^ ซ~ *
^ ^ * > *'-* -'Avian Acute Oral Toxicity Endings" ^ i ซ ^ ~ f
Species
Northern
Bobwhite
Mallard
% A.I.
93.3
21
LD5D rag/kg1
(cation
equivalent)
176(128.1)
199(144.8)
MRIDNo.
Author/Year
00029001
(Fink, et
al/1979)
00160000
(Hudson, et
al/1984)
Toxicity
Category
Moderately
toxic
Moderately
toxic
Fulfills
Guideline
Requiremen
t
Yes
Partial
'LDSD values given are in terms of technical paraquat dichloride not in terms of the cation
ป i , ^' . Avian Snbacute Dietary Toxicity findings > ^ i i ^
Species
Northern
Bobwhite
Ring-neck
Mallard
%A.I.
29.1
29.1
29.1
LCjuppm
(cation
equivalent)
981(714)
1468 (1068.5)
4048 (2946.3)
MRIDNo.
Author/Year
00022923
HilletaI/1975
00022923
Hilletal/1975
00022923
Hilletal/1975
Toxicity
Category
Moderately
toxic
Slightly toxic
Slightly toxic
Fulfills
Guideline
Requiremen
t
Yes
Yes
Yes
'The 29.1% test material is an end use product (paraquat dichloride CL) which contains 21.0% cation. The EP is prepared by diluting
the TGAI (paraquat dichloride concentrate, 43% cation) with water.
2LCSO values given are in terms of technical paraquat dichloride not in terms of the cation
These results indicate that paraquat dichloride is
moderately toxic to avian species on an acute oral and subacute
dietary basis. The guideline requirements are fulfilled. (MRIDs
00029001, 00022923, 00016000)
63
-------
(2) Birds, Chronic
Avian reproduction studies are required when
birds may be exposed repeatedly or continuously through
persistence, bioaccumulation, or multiple applications, or
if mammalian reproduction tests indicate reproductive
hazard. Present product labeling for use of paraquat
dichloride on a variety of crops allows several
applications of the end-use product per growing season.
The following table summarizes the avian reproduction
findings.
Avian Reproduction Finding^
Species
Northern
Bobwhite
Northern
Bobwhite
Mallard
Duck
/A.V
31.5
31.5
31.5
NOEC
ppm
100
100
30
LOEC
ppm
215
>100
(highest
level
tested)
100
Endpoints
affected
mortality
no effects
% viable
eggs, eggs
set,
normality of
hatchlings
and number
of 14-day
old survival
MRIDNo.
Author
/Year
00110453
Finket
al./1981
00110454
Fink et
al./1982
00110455
Fink et
al./1982
Fulfills
Guide-
line
Requir
e-ment
yes
partial
yes
. ana JLU.C,<_ values given in terms 01 tne cation not the technical paraquat dichloride
:V.a,L reflects % cation by weight
Additional data showed that significant mortality and reduced growth resulted
when mallard eggs were treated at 0.5 and 5.0 Ib cation/A. (MRID 00162746)
The avian reproductive studies indicate that paraquat dichloride can affect
reproduction or hatchability in birds when adult birds are exposed to more than 30
ppm of paraquat or when eggs are treated at 0.5 and 5.0 Ib ai./A. The guideline
requirements are fulfilled. (MRIDs 00110453, 00110454, 00110455, and 00162746)
64
-------
(3)
Mammals
Wild mammal testing is required on a case-by-case basis, depending on the
results of the lower tier studies such as acute and subacute testing, intended use
pattern, and pertinent environmental fate characteristics. In most cases, however, an
acute oral LD50 is used to determine toxicity to mammals. This LDSO is reported
below.
if ^ *
Mammalian Acute Oral Toxicity Findings
Species
Rat (small
mammal surrogate)
LD5I) mg/kg1
(cation equivalent)
344 (male) (250)
283 (female) (206)
MRID#
43685001
Toxicity Category
moderately toxic
'LD:o values given are in terms of technical paraquat dichloride not in terms of the cation.
The available mammalian data indicate that paraquat dichloride is moderately
toxic to small mammals on an acute oral basis. (MRID 43685001)
The table below shows the chronic toxicity of paraquat dichloride to
mammals.
- - * Chronic Toxicity to Mammals
Test Organism
^i
Fisher 344 Rats
Wistar Rats
Wistar-Derived
Alderley Park
Strain
Type of Study
Feeding/Carcinogenicity
Feeding/Carcinogenicity
Reproductive Toxicity
Duration
of Study
se^sm
113-124
wks
104 wks
11-12 wks
NOEL1
(ppm)
Eye
Opacity/Cataracts
Opacity/Cataracts
Lung Damage and
Mortality
25
100
25
MRID#
0013863
7
4021800
1
0012678
3
'NOEL data given in terms of cation
The available mammalian chronic data indicate paraquat
is lethal to some small mammals at levels below 25 ppm after 12
weeks of exposure.
65
-------
Additional data showed that exposure of rabbits to freshly
sprayed foliage can produce toxic symptoms and death. The
LD50 is 110 mg/kg for rabbit and 35 mg/kg for Belgian hare.
Also, the residues of paraquat measured in vegetation coupled
with evidence of pulmonary and lingual lesions demonstrate the
sensitivity of the hare to paraquat. (MRID 00162747, MRID
00162741)
(4) Insects
A honey bee acute contact LD50 study is required if the
proposed use will result in honey bee exposure. The available
insect acute contact toxicity findings are summarized in the
following table.
Nontarget Insect Acute Contact Toxicity Findings
Species
Honey
Bee
Honey
Bee
Honey
Bee
Honey
Bee
%AI
99% Tech. and
I,671b/galSC
(Gramoxone)
Technical
Technical
4 Ib ai./A spray
LD59 /jg a.L/bee1
Contact LDjo
>144 ug ai/bee
(tech)
= 72 ug ai/bee
(Gramoxone)
Oral LDM
51 ug ai/bee
(tech)
31 ug ai/bee
(Gramoxone)
2.74% mortality
at6.04//g/bee
contact LDM>
48/*g/bee
55% mortality
after 2 days and
90% after 3
days. (LDป Not
obtained)
MRID No.
Author/Year
43942603
Bull and
Wilkinson/1977
00028772
Atkins et
al./1973
05001991
Stevenson/
1978
00111488
Moffett et
al./1972
Toxicity
Category
practically
nontoxic
relatively
non-toxic
relatively
non-toxic
N/A
Fulfills
Guideline
Requirement
yes
yes
yes
supplemental
'Toxicity data are given in terms of technical paraquat dichloride not the cation.
There is sufficient information to characterize technical
paraquat dichloride and a formulated product as relatively non-
toxic to bees. The guideline requirement is fulfilled. (MRID#s
66
-------
00028772, 05001991, 00111488, 43942603). An additional
study showed that bees exposed to direct application of paraquat
dichloride CL at 4 Ibs cation/A caused 55% mortality within 2
days exposure and 99% mortality after 3 days exposure (MRID
00111488). This study was performed with an end-use product
of Paraquat dichloride and a surfactant. It is possible that the
surfactant caused paraquat to be more easily absorbed by the
honey bees resulting in the observed mortality.
b. Toxicity to Aquatic Animals
(1) Freshwater Fish
In order to establish the toxicity of a pesticide to
freshwater fish, the minimum data required on the technical
grade of the active ingredient are two freshwater fish toxicity
studies. One study should use a coldwater species (preferably
the rainbow trout), and the other should use a warmwater species
(preferably the bluegill sunfish). The 96-hour freshwater fish
acute toxicity findings for the technical grade of the active .
ingredient are summarized in the following table.
, * '< %'-T '> * > T >. t
f Freshwater Fish Acute Toxicity Findings
1* *- -s^h. *~ ^ ^
Species
Rainbow
trout
Bluegill
sunfish
Rainbow
Trout
Bluegill
sunfish
Rainbow
Trout
% A.I.
24% liquid
2 Ib. cation/gal
concentrate
24% liquid
2 Ib. cation/gal
concentrate
29.1 (cation)
29.1 (cation)
29.1
LCj, ppm a.i.1
15
13
38.68
156
29
. MRID No.
Author/year
40098001
Mayer, F.L. and
M.R.
Ellersieck/1986
40098001
Mayer, F.L. and
M.R.
Ellersieck/1986
00162736
Palmateer/1980
00162737
Palmateer/1979
00162738
McCann,
J./1977
Toxicity
Category
slightly
toxic
slightly
toxic
slightly
toxic
practically
non-toxic
slightly
toxic
Fulfills
Guideline
Requirement
yes
yes
yes
yes
yes
o values given are in terms of the cation not the technical paraquat dichloride.
67
-------
The results of the 96-hour acute toxicity studies indicate
that paraquat dichloride is slightly toxic to fish. The guideline
requirements are fulfilled. (MRID 40098001, 00162736,
00162737, 00162738)
Data from fish early life-stage tests or life-cycle tests are
required if the product is applied directly to water or expected to
be transported to water from the intended use site, and when the
pesticide is intended for use such that its presence in water is
likely to be continuous or recurrent regardless of toxicity; or if
any acute LC50 or EC50 is less than 1 mg/L; or if the EEC in water
is equal to or greater than 0.01 of any acute EC50 or LC50 value;
or if the actual or estimated environmental concentration in water
resulting from use is less than 0.01 of any acute EC50 or LC50
value and any of the following conditions exist: studies of other
organisms indicate the reproductive physiology offish and/or
invertebrates may be affected; or physicochemical properties
indicate cumulative effects; or the pesticide is persistent in water
(e.g. half-life greater than 4 days)..
Chronic fish studies are not required at this time because
paraquat dichloride is not registered for aquatic uses, is tightly
bound to soil, is not likely to be transported to aquatic
environments in significant quantities from runoff or drift and is
only slightly toxic to fish species.
(2) Freshwater Invertebrates
The minimum testing required to assess the hazard of a
pesticide to freshwater invertebrates is a freshwater aquatic
invertebrate toxicity test, preferably using first instar Daphnia
magna or early instar amphipods, stoneflies, mayflies, or midges.
The freshwater invertebrate toxicity findings are summarized in
the following table.
68
-------
Fresh water In vertebrate Toxicity Findings
Species
Daphnia
pulex
Daphnia
magna
Daphnia
magna
% A.I.
24% liquid
21b.
cation/gal
concentrate
92.3
29.1
EQo1
(ppm ai)
4.0
1.2
8.0
MRDONO.
Author/Year
40098001
Mayer, F.L. and
M.R.
Ellersieck/1986
00114473
Wheeler/1978
GS0262-028
Thompkins/1979
Toxicity
Category
Moderately
toxic
Moderately
toxic
Moderately
toxic
Fulfills
Guideline
Requirement
Yes
Yes
Yes
so values given are in terms of the cation not the technical paraquat dichloride.
There is sufficient information to characterize paraquat
dichloride as moderately toxic to aquatic invertebrates. The
guideline requirement is fulfilled. (MRID 40098001, 00114473,
GS0262-028)
(3) Estuarine and Marine Animals
Acute toxicity testing with estuarine and marine
organisms is required when an end-use product is intended for
direct application to the marine/estuarine environment or is
expected to reach this environment in significant concentrations.
Paraquat dichloride is not registered for aquatic use and is not
expected to reach the marine/estuarine environment in
significant concentration. Therefore, marine/estuarine studies
are not required at this time.
Toxicity to Plants
(1) Terrestrial
Currently, terrestrial plant testing (seedling emergence
and vegetative vigor) is required for herbicides which have
terrestrial non-residential outdoor use patterns and appear to
move off site of application through volatilization (vapor
pressure >1.0 x 10-5mmHg at 25ฐC) or drift (aerial or irrigation);
and/or which may have endangered or threatened plant species
associated with the site of application. Paraquat has a low vapor
pressure and extremely high adsorption coefficients such that it
69
-------
would not be expected to volatilize once applied to the soil.
However, some of the use patterns for paraquat dichloride may
allow off site movement as a result of drift from either ground or
aerial application, terrestrial plant testing is required.
Tier 2 Toxicity data on the TEP material for the most
sensitive species are summarized in the following table.
Nontarset Terrestrial Plant Toxicity Findings ' ,
Species
Dicot- CCoddebur)
Monocot- (Wheat)
%
A.I.'
29.4
29.4
Seedling emergence
EQs1 (Ibs cation/A)
0.85
X).86
Vegetative vigor
ECjs2
(Ibs cation/A)
0.013
0.061
'Expressed as ^Technical product not cation.
'Expressed as Ibs cation/A cation
The terrestrial plant testing guideline requirements are fulfilled. (MRID #
426396-01, 426010-01)
(2) Aquatic
Currently, aquatic plant testing is required for any herbicide which has outdoor
non-residential terrestrial uses that may result in offsite movement by runoff
(solubility >10 ppm in water), by drift (aerial or irrigation), or is applied directly to
aquatic use sites (except residential). Since the use patterns for paraquat dichloride
may allow offsite movement as a result of drift from either ground or aerial
application, aquatic plant testing is required.
The following species should be tested: Selenastrum capricornutum, Lemna
gibba, Skeletonema costatum, Anabaenaflos-aquae, and a freshwater diatom.
Tier 2 Toxicity data on the technical/TEP material are summarized in the
following table.
70
-------
^ "k. * * * ^^>^iS^ r J * ^ ซ
Nontarget Aquatic Plant Toxicity Findings *
s * -iZf-ff ""
Species
Mn>icu/a
pelliculosa
(Freshwater
diatom)
Lemnagjiia
Sefe/zas/noB
capricornutum
Skeletonema
costatum
Anabaenaflos-
QQUQS.
% A.I.1
32.7
32.7
32.7
32.7
32.7
NOEC/LOEC/EQ0
2(ppb)
0.22 / 0.45 /
O.SSppb
16/32/98ppb
0.08 / 0.20 /
0.32ppm
0.22 / 0.47 /
2.84ppm
3.2/6.3/15ppb
MRIDNO.
Author/Year
426010-06
Smyth etal/1992
426010-03
Smyth etal/1992
426010-02
Smyth etal/1992
426010-04
Smyth etal/1992
426010-05
Smyth etal/1992
Fulfills Guideline
Requirement
Yes
Yes
Yes
Yes
Yes
'Expressed as % Technical product not cation.
Expressed as ppb Technical
2.
The guideline requirements are fulfilled. (MRID #s 426010-02,
03, -04, -05, -06)
Environmental Fate
The environmental fate data base for paraquat dichloride is sufficiently
complete to make a thorough fate assessment for paraquat for the following
registered uses: terrestrial food crops (field, vegetable, and orchard), terrestrial
non-food crops (ornamentals and turf), terrestrial noncrop, forestry (directed
sprays in shelter belts and pine resin soaking), and domestic outdoor sites.
a.
Environmental Fate Assessment
The primary route of environmental dissipation of paraquat
dichloride is adsorption to biological materials and soil clay particles.
Paraquat dichloride has been shown to adsorb to clay crystalline lattices
with no apparent correlation between organic matter content and
paraquat adsorption. Paraquat dichloride does not hydrolyze, does not
photodegrade in aqueous solutions, and is resistant to microbial
degradation under aerobic and anaerobic conditions. Essentially no
microbial degradation of paraquat was seen after 180 days of aerobic
incubation or after 60 days of anaerobic incubation following a 30-day
aerobic incubation.
71
-------
Paraquat dichloride was shown to be very immobile in soil with
batch equilibrium studies conducted on four soils in the laboratory.
High rates of paraquat were added because at realistic field application
rates, paraquat was below detection in the batch equilibrium adsorption
solution. Adsorption Kd's ranged from 68-50,000 ml/g, and there was
no detectable desorption.
In laboratory studies with radiolabeled paraquat, no radioactivity
volatilized from the soil surface to adsorb to glass or to collect in
volatile traps. With low vapor pressure and extremely high adsorption
coefficients, paraquat would not be expected to volatilize once applied
to the soil. However, spray drift could potentially be a problem because
paraquat is extremely biologically active and toxic to plants and animals
before it becomes adsorbed to clay particles in the soil and therefore
biologically unavailable.
In short- and long-term field dissipation studies, paraquat
residues were extractable only by refluxing with 6 M sulfuric acid and
were shown to be persistent and to accumulate slightly with repeated
applications. Paraquat dichloride is inactivated (dissipated) by rapid
adsorption to clay particles. Due to the apparent adsorption strength of
paraquat for soil clays, these bound residues do not appear to be
environmentally available. Adsorbed radiolabeled paraquat did undergo
isotopic exchange when soil samples were shaken with a highly
concentrated, non-labeled paraquat solution (7440 ppm paraquat in
water). Therefore, the potential for desorption does exist; however,
since there was no apparent exchange with calcium chloride in the batch
equilibrium study, this exchange will probably not affect the
environmental behavior of paraquat.
Paraquat dichloride is very persistent and could potentially be
found in surface water systems associated with soil particles carried by
erosion. Paraquat dichloride is not expected to be a contaminant of
groundwater. A minor photodegradate, 4-carboxy-l-methylpyridinium
(QINA) which comprised 6% of applied radioactivity after 85 weeks of
natural sunlight irradiation, was determined to be mobile. According to
the field data reviewed in this submission, paraquat degraded very
slowly. Therefore, the minor photodegradate, QINA, would apparently
not be an important environmental concern.
72
-------
b. Environmental Fate, Chemistry, and Transport
(1) Degradation
(a) Hydrolysis (161-1)
The hydrolysis data requirement is fulfilled.
Paraquat dichloride at 91 ppm did not hydrolyze at pH 5,
7, and 9 when incubated at 25 or 40ฐ C. (Upton, Hendley,
and Skidmore, 1985. No MRID).
(b) Photodegradation in Water (161-2)
The photolysis in buffered solution data
requirement is fulfilled. Paraquat dichloride at 28 ppm in
sterile pH 7 aqueous buffer solution did not photodegrade
when continuously irradiated with a xenon arc lamp for
32 days at 25ฐ C. Paraquat dichloride accounted for 90.2-
98.0% of the applied radioactivity throughout the study in
the irradiated and dark control samples; no degradates
were reported from TLC or HPLC analyses. Volatiles
were trapped during this experiment and 0.15% of the
applied radioactivity was recovered as CO2. (MRID
40562301)
(c) Photodegradation on Soil (161-3)
The photodegradation on soil surfaces data
requirement is fulfilled. Paraquat dichloride did not
photodegrade when mixed with a sterile soil and exposed
to natural sunlight for 85 weeks. (Pack, 1982, no MRID).
(d) Aerobic soil metabolism (162-1)
The aerobic soil metabolism data requirement is
fulfilled. Paraquat dichloride at 4.32 ppm did not
degrade in sandy loam soil incubated under aerobic
conditions at 20 ฑ 2ฐ C for 180 days. Paraquat dichloride
comprised 93% of the applied radioactivity at 180 days
posttreatment. Most of the radioactivity was extracted
with technical grade paraquat by isotopic exchange.
There was no volatile radioactivity. No degradates were
73
-------
(2)
reported from TLC or HPLC analyses. (MRID
41319301)
(e) Anaerobic soil metabolism (162-2)
The anaerobic soil metabolism data requirement is
fulfilled. Paraquat dichloride at 4.32 ppm did not
degrade in sandy loam soil incubated under anaerobic
conditions for 60 days following a 30-day aerobic
incubation. Paraquat dichloride comprised 88.8% of the
applied radioactivity at 90 days posttreatment [60 days of
anaerobic incubation]. Most of the radioactivity was
extracted with technical grade paraquat by isotopic
exchange. A trace amount of radioactivity (0.29% of
applied) was recovered in the water phase at 61 days
posttreatment [30 days postflooding]. There was no
volatile radioactivity. No degradates were reported from
TLC or HPLC analyses. (MRID 41319302) .
(f) Anaerobic aquatic metabolism (162-3)
No studies were submitted; however, none are
required since an acceptable anaerobic soil metabolism
study was submitted.
(g) Aerobic aquatic metabolism (162-4)
Although no studies were required, one study was
submitted and reviewed in 1985. This study included an
aerobic-aquatic metabolism section with paraquat
dichloride applied to the surface of soil:water systems in
plastic swimming pools. Paraquat dichloride was
removed from the water column with a "resident half-
life" of <2 weeks. The soil layer was not sampled. This
study was considered scientifically valid, but does not
fulfill guideline requirements. (MRID 00055093)
Mobility
(a) Leaching, adsorption/desorption (163-1)
The unaged mobility data requirement is fulfilled.
Paraquat dichloride was immobile in silty clay loam,
74
-------
(3)
loam, loamy sand, and sand soils. It was not possible to
determine Freundlich Kads values because no paraquat
was detected in the adsorption solution at the lower
application rates. At high application rates (50-1000
times the field application rate), Kads values ranged from
at 68-50,000 ml/g . There was no desorption of paraquat
from these soils. (MRID 40762701)
The aged mobility data were not required.
Accumulation
The fish bioaccumulation data requirement was waived.
The logKow for paraquat dichloride is -4.5 at 20ฐ C indicating that
bioaccumulation is unlikely.
(4) Field Dissipation
The terrestrial field dissipation data requirement is
fulfilled with one short-term dissipation and four long-term
dissipation studies.
(a) Terrestrial field dissipation (164-1)
Paraquat dichloride degraded very slowly in
Delaware on a loamy sand soil which was planted to
soybeans. Residues decreased from an average of 1.1
mg/kg soil immediately posttreatment to 0.76 mg/kg at 86
days posttreatment and remained at 0.42-0.50 mg/kg
from 296 to 657 days posttreatment. Paraquat dichloride
did not leach below the 0- to 3.5-inch soil depth and was
only recovered at the detection limit of 0.05 mg/kg in the
4.5- to 10-inch soil segment from one subplot at 296 days
posttreatment.
(b) Dissipation Long term field (164-5)
Four long term field dissipation studies were
reported with data from: Champaign, Illinois (MRID
42802101); Visalia, California (MRID 42738701);
Leland, Mississippi (MRID 42738702); and Pikeville,
North Carolina (MRID 42802102). Paraquat dichloride
75
-------
c.
was applied in three or four single annual applications to
plots of bare ground, corn, peach trees, soybeans, and
cotton.
Acid-reflux extractable paraquat did not
appreciably degrade at any of the four sites from which
data were provided. Half-lives were not calculated in any
study although the study authors cited references of field
studies with paraquat half-lives of >10 years. In these
four studies, paraquat generally did not leach below the
3.5-inch depth.
Paraquat dichloride was stable for 1376 days (45
months) in soil samples treated at 1.0 mg/kg and stored
frozen at -14ฐ C. (MRID 42738703)
(c) Aquatic field dissipation (164-1)
No studies are required because there are no
aquatic uses for paraquat.
(5) Spray Drift
Spray drift data are required by 40 CFR Sec. 158.142
when aerial application and/or mist blower or other ground
application are proposed and it is expected that the effect levels
for nontarget organisms (humans, domestic animals, fish,
wildlife, and nontarget plants) expected to be present, are
exceeded.
Droplet size spectrum (201-1) and drift field evaluation
(202-1) data are required. The registrant (Zeneca) may elect to
satisfy these data requirements through the Spray Drift Task
Force, provided that these data are not required in advance of the
Task Force's final report. If the registrant wishes to satisfy these
data requirements in this manner, the procedures outlined in PR
Notice 90-3 should be followed.
Water Resources
Although there were detections of paraquat in drinking water
wells from two states cited in the Pesticides in Groundwater Database.
these detections are not considered to be representative of normal
76
-------
paraquat use. Paraquat dichloride binds strongly to soil clay particles
(Kd 68-50,000 mL/g) and did not leach from the surface in the
terrestrial field dissipation studies. Therefore, paraquat is not
considered to be a groundwater concern from normal use patterns.
3. Exposure and Risk Characterization
Paraquat dichloride is applied primarily as a broadcast treatment by
aerial and ground equipment but is also applied as a bark treatment, bore-hole
treatment, tree injection treatment, basal spray and spot treatment by a variety
of other methods. The non-broadcast treatment methods above, because of
limited application sites and application rates ranging from 3.3 x 10"4 to 1 Ib
cation/A, are not expected to pose significant risk to non-target wildlife and
will not be considered further in this risk assessment. Instead, the Ecological
Exposure and Risk Characterization that follows will be concerned only with
the aerial and ground broadcast application uses of paraquat dichloride and
their effect on non-target and endangered species.
a. Ecological Exposure and Risk Characterization
Explanation of the Risk Quotient (RQ) and the Level of Concern
(LOC): The Levels of Concern are criteria used to indicate potential
risk to nontarget organisms. The criteria indicate that a chemical, when
used as directed, has the potential to cause undesirable effects on
nontarget organisms. There are two general categories of LOC (acute
and chronic) for each of the four nontarget faunal groups and one
category (acute) for each of two nontarget floral groups. In order to
determine if an LOC has been exceeded, a risk quotient must be derived
and compared to the LOC's. A risk quotient is calculated by dividing an
appropriate exposure estimate, e.g. the estimated environmental
concentration, (EEC) by an appropriate toxicity test effect level, e.g. the
LC50. The acute effect levels typically are:
-EC25 (terrestrial plants),
-EC50 (aquatic plants and invertebrates),
-LC50 (fish and birds), and
-LDSO (birds and mammals)
The chronic test results are the:
-NOEL (or the NOEC) for avian and mammal reproduction studies, and
either the NOEL for chronic aquatic studies, or the Maximum
Allowable Toxicant Concentration (MATC), which is the geometric
77
-------
mean of the NOEL and the LOEL (or LOEC) for chronic aquatic
studies.
When the risk quotient exceeds the LOG for a particular category, risk
to that particular category is presumed to exist. Risk presumptions are
presented along with the corresponding LOC's.
Levels of Concern (LOG) and associated Risk Presumption
Mammals, Birds
IF THE
acute
acute
acute;
chronic RQ:
Fish, Aquatic invertebrates
IF THE
acute RQ^
acute RQk
LOG
0.5
0.2
0.1
1
acute
LOG
0.5
0.1
0.05
chronic RQ
Plants
IF THE
RQ:>
RQk
LOG
1
1
PRESUMPTION
High acute risk
Risk that may be mitigated
through restricted use
Endangered species may be
affected acutely
Chronic risk, endangered
species may be affected
chronically,
PRESUMPTION
High acute risk
Risk that may be mitigated
through restricted use
Endangered species may be
affected acutely
Chronic risk, endangered
species may be affected
chronically
PRESUMPTION
High risk
Endangered plants may be
affected
Currently, no separate criteria for restricted use or chronic effects for
plants exist.
78
-------
(1) Exposure and Risk to Nontarget Terrestrial Animals
(a) Birds
Acute
Residues found on dietary food items following
paraquat dichloride application may be compared to LC50
values to predict acute risk. The maximum estimated
environmental concentrations (EECs) of residues of
paraquat dichloride which may be expected to occur on
selected avian or mammalian dietary food items
following a single application are provided in the table
below along with the respective risk quotients (RQs) and
pertinent LOCs.
Avian RQs based on aBpbwhite juail IXJ, of 714 ppm (cation)
Food items
Short Grass
Long Grass
Broadleaf Plants/
Small Insects
Fruits/
Large Insects/
Seeds
Maximum Application Ratej
(Ibs cation/A)
0.07
1.0
1.6
0.07
1.0
1.6
0.07
1.0
1.6
0.07
1.0
1.6
EEC
(PPซn)
(cation)
16.80
240.00
384.00
7.70
110.00
176.00
9.45
135.00
216.00
1.05
15.00
24.00
RQ
(EEC/
LQo)
0.02
0.34**
0.54***
0.01
0.15
0.25**
0.01
0.19*
0.30**
0.00
0.02
0.03
'U.U71D/A = lowest maximum application rate for broadcast uses
1.0 Ib/A - typical maximum application rate for food and non-food/non-feed uses
1.6 Ib/A = absolute maximum application rate for various food uses
* Exceed Endangered species (ESP) LOC (ESP LOCiO.l)
*.* Exceeds ESP LOCaO.l and Restricted Use (RU) LOCs (RU LOCxO.l and sO.2)
*** Exceeds ESP, RU and High Acute Risk (HR) LOCs (HR LOC>0.5)
79
-------
Results indicate that the high acute risk, restricted
use and endangered species LOCs are exceeded for birds
at application rates at or above 1.49, 0.60 and 0.3 Ibs
cation/A respectively. Therefore the use of paraquat
dichloride at higher rates is expected to pose acute risk to
non-target avian species. However, because of the
environmental fate of the chemical, the risk posed by
paraquat only exists shortly after application. Once the
applied paraquat has dried (usually within 4 hours), its
risk is greatly reduced. It should be noted that the
potential exists for the paraquat to again pose risk as a
result of rewetting by rain, dew or humidity but at a much
lower level.
Chronic
Residues found on dietary food items following
paraquat dichloride application may be compared to
NOEC values to predict chronic hazard. The maximum
estimated environmental concentration (EEC) of residues
of paraquat dichloride which may be expected to occur
on selected avian dietary food items following a single
application is provided in the table below along with the
respective risk quotients (RQs) and pertinent LOCs.
Chronic Risk Quotients (RQs) based on a Mallard duck NOEL of 30 ppm (cation)
(RQs1 and EECs expressed as cation)
Food items
Short Grass
Long Grass
Broadlcaf Plants/
Small Insects
Maximum Application
Rates2
(Ibs cation VA )
0.07
1.0
1.6
0.07
1.0
1.6
0.07
1.0
1.6
EEC
(ppm)
16.80
240.00
384.00
7.70
110.00
176.00
9.45
135.00
216.00
RQ
(EEC/
NOEL)
0.56
8.00*
12.80*
0.26
3.67*
5.87*
0.32
4.50*
7.20*
80
-------
Chronic Risk Quotients (RQs) based on a Mallard Indc" NOEL oฃ3*0 ppm (cation)
-, * "" * 'iORQsVand'JjECs expressed as tuition)
. * t &* * * * * i
Food items
Fruits/Large Insects/
Seeds
Maximum Application
Rates2
(Ibs cation./A )
0.07
1.0
1.6
EEC
(ppm)
1.05
15.00
24.00
RQ
(EEC/
NOEL)
0.04
0.50
0.80
1 0.071b/A = lowest maximum application rate for broadcast uses
1.0 Ib/A = typical maximum application rate for food and non-food/non-feed uses
1.6 Ib/A = absolute maximum application rate for various food uses
* Exceeds Chronic Risk LOG
The above table shows that at rates of 1.0, and 1.6
Ibs cation/A the chronic LOCs for avian species are
exceeded. Normally this would indicate a chronic risk to
birds. However, the environmental fate data indicate that
once paraquat is applied and dries, it is not expected to
pose a risk. If it is washed off plant surfaces, it is very
strongly adsorbed to clay particles in the soil and
therefore not biologically available. Therefore, the
registered uses of paraquat dichloride are not expected to
pose a chronic risk to avian species.
Although a chronic risk is not expected as the
result of residues on dietary food items, the Agency is
concerned that the use of paraquat dichloride may affect
avian reproduction. There is evidence to show that
following direct application at rates of 0.5 and 5.0 Ibs
cation/A to mallard duck eggs, paraquat can cause a
reduction of hatchability, significant mortality and
reduced growth (MRIDs 00110453, 00110454,
00110455,00162746).
(b) Mammals
Acute
Small mammal exposure is addressed using acute
oral LD50 values converted to estimate a LC50 value for
dietary exposure. The estimated LC50 is derived using the
following formula:
50
LD,
-50-
% of body weight consumed
81
-------
Mammals can be separated into five general
groups according to food habits: herbivores, insectivores,
granivores, omnivores and carnivores. For the purposes
of this risk assessment only three groups will be
considered; herbivores, insectivores and granivores.
Risk quotients were calculated using the
calculated LC50's and the EEC's for the 0.07, 1.0, and 1.6
Ibs cation/A application rates. These are summarized
along with the LOG exceedances in the following tables.
82
-------
Appl.
Rate
Ibs
cation/A
0.07
1.0
1.6
Weight
(g)
15
35
1000
15
35
1000
15
35
1000
Consumed
95
66
IS
95
66
15
95
66
15
mg/kg/d
in diet
216.84
312.12
1 373 33
216.84
312.12
1 373 33
216.84
312.12
1 373 33
Short Grass
16.80
240.00
384.00
J3l^(J
Broadleaf
Plants/
Small
Tn*?pf*t^
9.45
135.00
216.00
iifctj
Fruits and
Large
Insects
1.05
15
24
Ky
Short Grass
0.08
0.05
1.11
***
0.77
***
1.77
***
1.23
***
078**
K.V
Broadleaf
Plants/
Small
0.04
0.03
o m
20.62
***
0.43**
0 10*
1.00
***
0.69
***
0 Ifi*
Ky
Fruits and
Large
Insects
0.00
0.00
0.07
0.05
0 01
0.11*
0.08
E/xceeuS JioJr
** Exceeds RU and ESP LOCs
*** Exceeds HR.RU and ESP LOCs
Appl. Rate
Ibs cation /A
0.07
1.0
1.6
Mammalian (jranivoreKQs (based on s female rat U^ of 206 mg/fcg) and ฃJฃCs expressed as- cation
Body Weight
M
15
35
15
35
15
35
%Bodywt.
fon^uiYisH
21
15
3
21
15
21
15
^
Est mg/kg/d
iti dipt
980.95
1,373.33
6 86667
980.95
1,373.33
6 866 67
980.95
1,373.33
6 R66 67
EEC seeds
1.05
15
24.00
RQ
0.00
0.00
000
0.02
0.01
0.02
0.02
The two tables above show that for the lowest
application rate, 0.07 Ibs cation/A, no LOCs are exceeded
for any exposure scenarios. As such, at application rates
of 0.07 Ibs cation/A or below, the registered uses of
Paraquat dichloride are not expected to pose acute risk to
non- endangered mammalian species. Also, the
registered uses of Paraquat dichloride are not expected to
pose acute risk to any granivorous mammals at
application rates up to and including 1.6 Ibs a.i./L.
The application rate of 1.0 Ibs cation/A may
produce residues on grass that result in risk quotients that
exceed HR, RU and ESP LOCs for small and medium
herbivorous and small insectivorous mammals. Restricted
use LOCs are exceeded for medium insectivorous
mammals. Endangered species LOCs are exceeded for
large herbivorous and insectivorous mammals. The
highest application rate of 1.6 Ibs cation/A (food and feed
uses) produces residues in grass that result in risk
83
-------
quotients that exceed HR, RU and ESP LOCs for small
and medium herbivorous and insectivorous mammals,
restricted use LOCs for large herbivorous mammals and
endangered species LOCs for large insectivorous
mammals. However, because of the environmental fate
of the chemical, the risk posed by paraquat only exists
shortly after application. Once the applied paraquat has
dried, its risk is greatly reduced. It should be noted that
the potential exists for paraquat to again pose risk as a
result of rewetting by rain, dew or humidity, but this risk
is at a much lower level.
Chronic
Residues found on dietary food items following
paraquat dichloride application may be compared to
NOEC values to predict chronic risk. The maximum
estimated environmental concentrations (EECs) of
residues of paraquat dichloride which may be expected to
occur on selected mammalian dietary food items
following a single application is provided in the table
below along with the respective risk quotients (RQs) and
pertinent LOCs. The EECs and the RQs are summarized
in the following table.
84
-------
Chrome nsk quotients based on a 12 week study with Wistar-Derived Alderley PartStrain Rats resulting in a NOEL oฃ25 ppm-{cation) and EECs (expressed as
-'' cation) - ,
Food items
Short Grass
Long Grass
Broadleaf Plants
Fruits
Maximum Application Rates'
(Ibs cation/A )
0.07
1.0
1.6
0.07
1.0
1.6
0.07
1.0
1.6
0.07
1.0
1.6
EEC
(ppm)
16.80
240.00
384.00
7.70
110.00
176.00
9.45
135.00
216.00
1.05
15.00
24.00
RQ
(EEC/NOEL)
0.67
9.6*
15.36*
0.31
4.4*
7.04*
0.38
5.4*
8.64*
0.04
0.60
0.96*
'0.071b/A = lowest maximum application rate for broadcast uses
1.0 Ib/A = typical maximum application rate for food and non-food/non-feed uses
1.6 Ib/A = absolute maximum application rate for various food uses
* Exceeds Chronic LOC
The above table shows that at rates of 1.0, and 1.6
Ibs cation/A the chronic LOCs for mammals are
exceeded. Normally this would indicate a chronic risk to
mammals. However, environmental fate data indicate
that paraquat once applied and dried is not expected to
pose risk and if washed off plant surfaces is very strongly
adsorbed to clay particles in the soil and therefore not
biologically available. Therefore, the registered uses of
paraquat dichloride are not expected to pose a chronic
risk to mammalian species.
(c) Insects
Laboratory data indicates that, based on the
application of dry crystalline and liquid formulations of
technical and Technical End-Product (TEP) Paraquat
dichloride, the contact LDSO to honey bees ranged from
6.04->144 ug/bee. This classifies Paraquat dichloride as
relatively non-toxic to bees. Another study (MRID#
#00111488) shows that when Paraquat dichloride CL
(formulated product) was sprayed on honey bees at the
rate of 4 Ibs cation/A, 55% mortality was observed after 2
days and 90% mortality after 3 days. The study, in which
Paraquat in combination with a surfactant was sprayed at
rates 2.5 to 4 times maximum label rates, seems to
indicate that potential for risk to honey bees may exist as
85
-------
a result of direct contact with paraquat sprayed at labeled
rates. However, the extent of the risk, if any, is expected
to be very minimal because paraquat technical is
classified as relatively nontoxic to honey bees and
because, for most of the major uses, paraquat will be
applied at times when honey bees will not be active in the
field
(2) Exposure and Risk to Nontarget Aquatic Animals
Risk to nontarget aquatic animals is assessed by
comparing actual or estimated environmental concentrations
(EECs) to toxicity data and calculating Risk Quotients (RQs).
These RQs are then compared to the LOCs to assess the potential
for risk to non-target aquatic animals. Aquatic EECs are
generally considered the result of direct application to water or
the additive effect of runoff or drift. The EECs used in risk
assessments are usually obtained either by utilizing the GENEEC
Model as an initial screening tool or more advanced models to
obtain more refined values. Both types of models utilize fate
data including hydrolysis and photolysis half lives, Koc, Kads,
solubility, etc. Because paraquat dichloride dissipates by
binding very strongly to clay minerals in soils, using models that
depend on degradation parameters would yield inappropriate
EEC predictions. Due to paraquat dichloride's strong adsorption
to soil, no aquatic residues are expected as a result of runoff.
The only residues expected are those resulting from drift of
paraquat dichloride during application. The following formula
was used to calculate EECs due to drift.
EEC = Application Rate X "/(.drift1 X 61ppb2
The following table lists the EECs and resultant RQs
expected following application of paraquat dichloride at
registered label rates.
'Values used are; 1% drift for ground application and 5% drift for aerial application
*Ihc concentration of a pesticide expected in a 1 Acre pond, 6 ft. deep, following application of 1 Ib/A.
86
-------
Application Rate
(Ib/A)
0.07
1
1.6
- ' AculetlStlitflgB^^
Drift
Ground
Application
(Ib cation/Ay
0.001
0.010
0.016
Drift
Aerial Application
(Ib cation/A)1
0.004
0.050
0.080
Exposure Scenario
Residues from
Ground
Application (ppbf
0.043
0.610
0.976
Residues from
Aerial Application
(ppb)2
0.214
3.050
4.880
RQs
(Ground
Application)
0.000
0.001
0.001
RQs
(Aerial
Application)
0.000
0.003
0.00
'Values used are; 1% drift for ground application and 5% drift for aerial application
'The concentration of a pesticide expected in a 1 Acre pond, 6 ft deep, following application of 1 Ib/A.
Comparing the RQs to the LOCs (High acute risk LOG ฃ 0.5;
Restricted Use LOG ฃ 0.1; Endangered species LOG ^ 0.05), no LOCs are
exceeded. Therefore, the registered uses of paraquat dichloride are not
expected to pose an acute risk to any aquatic organisms.
(3) Exposure and Risk to Nontarget Plants
(a) Terrestrial and Semi-aquatic
Non-target terrestrial plants inhabit areas which are dry. Non-target
semi-aquatic plants are plants that usually inhabit low-lying wet areas that may
be dry in certain times of the year. These plants are not obligatory aquatic
plants in that they do not live in a continuously aquatic environment. The
terrestrial and semi-aquatic plants may be exposed to pesticides from runoff,
drift or volatilization.
Spray drift exposure from ground and aerial application (including
airblast, forced-air, and chemigation applications) is assumed to be 1 and 5%
respectively, of the application rate.
As was stated previously, paraquat dichloride binds strongly to soil and
it is therefore not expected to affect non-target terrestrial and semi-aquatic
plants as a result of runoff. Therefore, the risk of the use of paraquat
dichloride to non-target terrestrial and semi-aquatic plants is expected to come
only as a result of drift during application. The EECs were calculated using
the following formulas:
EEC Formulae
Calculating EECs for terrestrial plants inhabiting areas adjacent to treatment
sites:
87
-------
Unincorporated ground application:
Drift = maximum application rate x 0.01
Aerial, airblast, forced-air, and chemigation applications:
Drift = maximum application rate (Ibs cation/acre) x 0.05
Calculating EECs for semi-aquatic plants inhabiting wet, low-lying areas:
Unincorporated ground application:
Drift = maximum application rate x 0.01
Aerial, airblast, and forced-air applications:
Drift = maximum application rate (Ibs cation/acre) x 0.05
To assess risk, the EECs are then compared to the EC25 of the most
sensitive plant species, the Cocklebur (EC2S = 0.013 Ib cation/A. The RQs are
then compared to the LOG for plants (LOC=1). The following table lists
EECs and RQs for the registered label rates of paraquat dichloride.
88
-------
' Acate High Risk Quotient (RQs) for Terrestrial and Semi-Ac(uaticJPlants
, (based on a Cocklebur vegetative vigor EQ, of 0.0 13 Ibs cation/A)
Application Rate
(Ib/A)
(cation)
0.0700
1.0000
1.6000
Unincorporated
Ground
Application EECs
(Ib cation/A)
0.00
0.01
0.02
Aerial Application EECs
(Ib cation/A)
0.00
0.05
0.08
Terrestrial &
Semi-Aquatic Rqs
(Ground
Application)
0.00
0.77
1.54*
Terrestrial &
Semi-Aquatic Rqs
(Aerial
Application)
0.00
3.85*
6.15*
* Exceeds LOG
The use of paraquat dichloride is not expected to
pose risk to non-target terrestrial and semi-aquatic plants
at the lowest application rate of 0.07 Ib cation/A. Aerial
application of paraquat dichloride at the 1.0 Ib cation./A
rate is expected to pose risk to non-target terrestrial and
semi-aquatic plants due to drift. Ground application at
the same rate is not expected to pose risk. At the
maximum rate of 1.6 Ib cation/A both aerial and ground
application of paraquat dichloride are expected to pose
risk to non-target plants.
Acute Endangered Species Risk Quotient (RQs) for Terrestrial and Semi-Aquatic Plants
(based on a Cocklebur vegetative vigor NOEL of 0.004 Ibs cation/A)
Application Rate
(Ib/A)
(cation)
0.0700
1.0000
1.6000
Unincorporated
Ground
Application EECs
(Ib cation/A)
0.00
0.01
0.02
Aerial Application EECs
(Ib cation/A)
0.00
0.05
0.08
Terrestrial &
Semi-Aquatic Rqs
(Ground
Application)
0.00
2.50*
5.00*
Terrestrial &
Semi-Aquatic Rqs
(Aerial
Application)
0.00
12.50*
20.00*
* Exceeds LOG
The use of paraquat dichloride is not expected to
pose risk to endangered terrestrial and semi-aquatic plants
at the lowest application rate of 0.07 Ib cation/A. Aerial
and ground application of paraquat dichloride at the 1.0
Ib cation ./A rate and above are expected to pose risk to
endangered terrestrial and semi-aquatic plants due to
drift.
(b) Aquatic Plants
Exposure to nontarget aquatic plants may occur
through runoff or spray drift from adjacent treated sites
or, directly from such uses as aquatic weed or mosquito
larvae control. An aquatic plant risk assessment is
usually done for aquatic vascular plants from the
surrogate duckweed Lemna gibba. Non-vascular aquatic
plant risk assessments are performed using either algae or
89
-------
diatom, whichever is the most sensitive species. These
non-vascular plants are useful to determine impact to
food sources of aquatic organisms. Only short term risk
to aquatic plants is estimated. The risk ratio is
determined by dividing the pesticide's initial
concentration in water by the pesticide's EC50 for each
surrogate species.
As was stated previously, paraquat dichloride
binds strongly to soil and it is therefore not expected to
affect non-target aquatic plants as a result of runoff. The
risk of the use of paraquat dichloride to non-target aquatic
plants is expected to come only as a result of drift during
application. In the case of submerged aquatic plants,
such as aquatic algae, diatoms, and submerged
macrophytes, paraquat dichloride exposure results from
aquatic residues resulting from spray drift. In the case of
floating aquatic plants, such as duckweed, waterlilies,
etc., exposure results not only from aquatic residues but
also from direct contact with pesticide drift. The
following table lists the EECs expected resulting from
ground and aerial application of paraquat dichloride at
registered label rates. The EECs were calculated using
the same formulas as used for the aquatic organism risk
assessment and only reflect aquatic residues resulting
from spray drift.
Acute RQ's and EEC's for duckweed and the
diatom, Navicula petticulosa, are shown in the Tables
below.
90
-------
Estimated Environmental Concentrations (EECs) and Acute Risk Quotients (RQ) for Aquatic Planfeased upon a duckweed EC50 of 0.0713 ppm and a non
vascular-plant the AiatomNaviculapeUiculosa'ECSO of 0.^40 ppl>. " '
Rate of
Application
(Ib cation/A)
0.07
1
1.6
Surrogate Plant
duckweed
Lemna gibba
diatom
Navicula
pelliculosa
duckweed
Lemna gibba
diatom
Navicula
pelliculosa
duckweed
Lemna gibba
diatom
Navicula
pelliculosa
EC*
(ppb)
71.3
0.4
71.3
0.4
71.3
0.4
Aquatic
Residue in 6' of
Water from
Drift from
Ground
Application
(ppb)
0.04
0.61
0.98
Aquatic
Residue in &
of Water from
Drift from
Aerial
Application
(ppb)
0.21
3.05
4.88
RQ
(Ground
Application)
(EEC/
EC50)
0.0006
0.1000
0.0086
1.5250
0.0137
2.45
RQ
(Aerial
Application)
(EEC/
EC50)
0.0029
0.5250
0.0428
7.6250
0.0684
12.2000
The above results indicate that for aquatic plants
high acute risk LOCs are not exceeded for rates equal to
or below 1.6 Ib cation/A for non-target vascular plants as
a result of ground or aerial applications of paraquat
dichloride. Aquatic plants high acute risk LOCs are not
exceeded for rates equal to or below 0.07 Ib cation/A for
non-target non-vascular plants as a result of ground or
aerial applications of paraquat dichloride, but are
exceeded at the 1.0 and 1.6 Ib cation/A rates. Currently,
no separate criteria for restricted use or chronic effects for
plants exist.
In order to assess the risk of paraquat dichloride to
endangered plants, the same formulas were used to
calculate the EECs. However, the RQs were calculated
using NOEC values in the place of EC50 values and are
summarized in the following table.
91
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' 'iVM'*1! '
Estimated EnvirontncnUI Concentrations (EECs) and Enaangered Species Risk Quotients (RQ) for Aqna tic Plants based aponti&emnagibbaNQECof ' !|
ปPJ*. ''''',, ,'i !'H> ',ซ,!
Rate of
Application
(Ib cation/A)
0,07
1
1.6
Surrogate Plant
Lemnagibba
Lemnagibba
Lemnagibba
NOEC
(ppb)
11.6
11.6
11.6
Aquatic
Residue in 6'
of Water from
Drift from
Ground
Application
(ppb)
0.04
0.61
0.98
Aquatic
Residue in 6'
of Water from
Drift from
Aerial
Application
(ppb)
0.21
3.05
4.88
RQ
(Ground
Application)
(EEC/
EC50)
0.00
0.05
0.08
RQ
(Aerial
Application)
(EEC/
EC50)
0.02
0.26
0.42
Based on the calculated RQs, the LOCs are not exceeded
for endangered aquatic plants. Therefore, the registered uses of
paraquat dichloride are not expected to pose risk to non-target
endangered aquatic plants.
(4) Endangered Species
Levels of Concern have been exceeded for endangered
species of birds at application rates greater than or equal to 0.30
Ib cation/A. Levels of Concern have also been exceeded for
endangered mammalian species for all labeled application rates >
0.55 Ib cation/A. These risks exist only until the paraquat
dichloride residue dries or becomes bound.
LOCs for endangered aquatic organisms have not been exceeded
at even the highest rate of 1.6 Ibs cation/A. Levels of Concern
have been exceeded for endangered terrestrial and semi-aquatic
plants at the 1.0 Ib cation/A application rate. The endangered
species LOCs for aquatic plants are exceeded at the 1.0 and 1.6
Ib cation/A rates for ground application and at all rates for aerial
application.
When the Endangered Species Protection Program
becomes final, limitations in the use of paraquat dichloride may
be required to protect endangered and threatened species, but
these limitations have not been defined and may be formulation
specific. The Agency anticipates that a consultation with the
Fish and Wildlife Service may be conducted in accordance with
the species-based priority approach described in the Program.
After completion of consultation, registrants will be informed if
any required label modifications are necessary. Such
modifications would most likely consist of the generic label
92
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statement referring pesticide users to use limitations contained in
county Bulletins.
IV. RISK MANAGEMENT AND REREGISTRATION DECISION
A. Determination of Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after
submission of relevant data concerning an active ingredient, whether products
containing the active ingredients are eligible for reregistration. The Agency has
previously identified and required the submission of the generic (i.e. active ingredient
specific) data required to support reregistration of products containing paraquat
dichloride as an active ingredient. The Agency has completed its review of these
generic data, and has determined that the data are sufficient to support reregistration of
all products containing paraquat dichloride under the conditions specified in the RED.
Appendix B identifies the generic data requirements that the Agency reviewed as part
of its determination of reregistration eligibility of paraquat dichloride, and lists the
submitted studies that the Agency found acceptable.
The data identified in Appendix B were sufficient to allow the Agency to assess
the registered uses of paraquat dichloride and to determine that paraquat dichloride can
be used without resulting in unreasonable adverse effects to humans and the
environment if used according to the label as amended by this RED. The Agency
therefore finds that all products containing paraquat dichloride as the active ingredient
are eligible for reregistration under the conditions specified in this RED. The
reregistration of particular products is addressed in Section V of this document.
The Agency made its reregistration eligibility determination based upon the
target data base required for reregistration, the current guidelines for conducting
acceptable studies to generate such data, published scientific literature, etc. and the
data identified in Appendix B. Although the Agency has found that all uses of
paraquat dichloride are eligible for reregistration under the conditions specified in this
RED, it should be understood that the Agency may take additional appropriate
regulatory action, and/or require the submission of additional data to support the
registration of products containing paraquat dichloride, if new information comes to
the Agency's attention or if the data requirements for registration (or the guidelines for
generating such data) change.
B. Determination of Eligibility Decision
1. Eligibility Decision
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The Agency has determined that paraquat dichloride products, labeled
and used as specified in this Reregistration Eligibility Decision, will not pose
unreasonable risks or adverse effects to humans or the environment. Under the
Food Quality Protection Act of 1996, the Agency has determined that there is a
reasonable certainty that no harm will result to infants and children from
aggregate exposure to paraquat dichloride. There are no residential uses of
paraquat dichloride, therefore, there are no risks of dermal or inhalation
exposure to infants, children or the general population. Additionally, paraquat
is not expected to be a contaminant of drinking water. The Agency has also
concluded that there are no other chemicals with a common mode of toxicity as
that of paraquat. Therefore, the Agency concludes that products containing
paraquat dichloride for all uses are eligible for reregistration as specified in this
RED.
2. Eligible and Ineligible Uses
The Agency has determined that all uses of paraquat dichloride are
eligible for reregistration under the conditions specified in this RED.
C. Regulatory Position
The following is a summary of the regulatory positions and rationales for
paraquat dichloride. Where labeling revisions are imposed, specific language is set
forth in Section V of this document.
I. Food Quality Protection Act Findings
a. Determination of Safety for U.S. Population
EPA has determined that the established tolerances with
amendments and changes as specified in this document for paraquat
meet the safety standards under the FQPA amendments to section
408(b)(2)(D) for the general population. In reaching this determination,
EPA has considered the available information on the aggregate
exposures (both acute and chronic) from non-occupational sources, food
and drinking water, as well as the possibility of cumulative effects from
paraquat and other bipyridylium compounds that may have a similar
mode/mechanism of toxicity.
Since there are no residential or non-occupational uses of ,
paraquat, no dermal or inhalation exposure is expected in and around
the home. Additionally, paraquat residues are not expected to be found
in either groundwater or drinking water.
94
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No acute toxicity endpoints of concern have been identified for
paraquat.
The chronic dietary risk assessment showed the percent of the
RfD utilized by dietary exposure to residues of paraquat is 10% for the
general U.S. population. Therefore, the Agency concludes that
aggregate risks for the general population resulting from paraquat uses
are not of concern.
In evaluating the potential for cumulative effects, EPA compared
structural similarities and toxic effects seen in paraquat studies with
other bipyridylium compounds such as diquat dibromide. The Agency
determined that diquat and paraquat have different effects. Paraquat is a
lung toxicant and diquat is not. Paraquat appears to be a weaker
cataractogenic agent then diquat. Therefore, based on available data the
Agency does not believe that the toxic effects produced by paraquat
would be cumulative with the toxic effects produced by diquat.
b. Determination of Safety for Infants and Children
EPA has determined that the established tolerances for paraquat,
with amendments and changes as specified in this document, meet the
safety standards under the FQPA amendments to section 408(b)(2)(C)
for infants and children. The safety determination for infants and
children considers the factors noted above for the general population,
but also takes into account the possibility of increased dietary exposure
due to the specific consumption patterns of infants and children, as well
as the possibility of increased susceptibility to the toxic effects of
paraquat residues in this population subgroup.
In determining whether or not infants and children are
particularly susceptible to toxic effects from paraquat residues, EPA
considered the completeness of the database for developmental and
reproductive effects, the nature and severity of the effects observed, and
other information.
Based on the current data requirements, paraquat has a complete
database for developmental and reproductive toxicity. In the
developmental studies effects were seen (delayed ossification in the
forelimb and hindlimb digits) in the fetuses only at the same or higher
dose levels than effects in the mother. In the reproduction study, no
effects on reproductive performance were seen. Also because the
NOELs from the developmental and reproduction studies were equal to
95
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2.
or greater than the NOEL used for establishing the reference dose, EPA
concludes that it is unlikely that there is additional risk concern for
immature or developing organisms. Finally, the Agency has no
epidemiological information suggesting special sensitivity of infants and
children to paraquat. Therefore, the Agency finds that the uncertainty
factor (100X) routinely used in RfD calculations is adequately
protective of infants and children, and an additional uncertainty factor
is not warranted for paraquat.
EPA estimates that paraquat residues in the diet of non-nursing
infants (less than 1 year) account for 31% of the RfD and 24% of the
RfD for children aged 1-6 years. Further, residues in drinking water are
not expected. Therefore, the Agency has determined that there is
reasonable certainty that dietary exposure to paraquat will not cause
harm to infants and children.
In deciding to continue to make reregistration determinations
during the early stages of FQPA implementations, EPA recognizes that
it will be necessary to make decisions relating to FQPA before the
implementation process is complete. In making these early, case-by -
case decisions, EPA does not intend to set broad precedents for the
application of FQPA to its regulatory determinations. Rather, these
early decisions will be made on a case-by-case basis and will not bind
EPA as it proceeds with further policy development and rulemaking that
may be required.
If EPA determines, as a result of this later implementation .
process, that any of the determinations described in this RED are no
longer appropriate, the Agency will consider itself free to pursue
whatever action may be appropriate, including but not limited to,
reconsideration of any portion of this RED.
Tolerance Reassessment
The tolerances listed in 40 CFR ง180.205(a) are expressed in terms of
residues of paraquat derived from application of either the bis(methyl sulfate)
or the dichloride salt (both calculated as a cation). A summary of paraquat
tolerance reassessments is presented below in table form.
Sufficient data are available to ascertain the adequacy of the established
tolerances for the following commodities, as defined in 40 CFR ง180.205(a):
acerola; almond hulls; apples; apricots; asparagus; avocados; bananas; barley
grain; bean straw; beans, dry; beans, forage; beans, hay; beans, lima
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(succulent); beans, snap (succulent); beets, sugar; beets, sugar (tops); broccoli;
cabbage; cacao beans; carrots; cauliflower; cherries; Chinese cabbage; citrus
fruit; coffee beans; collards; corn, fresh (inc sweet corn) (K + CWHR); corn
grain; cottonseed; cucurbits; eggs; figs; guar beans; guava; kiwifruit; lettuce;
mint, hay; nectarines; nuts; olives; onions, dry bulb; onions, green; papayas;
passion fruit; peaches; peanuts; peanut, hay; peanut, hulls; peanut, vines; pears;
peas (succulent); peas, forage; peas, hay; pineapples; pistachio nuts; plums
(fresh prunes); potatoes; poultry, fat; poultry, meat; poultry, mbyp; rhubarb; rye
grain; safflower seed; small fruit; sorghum gram; soybean forage; soybeans;
strawberries; sugarcane; sunflower seeds; turnips (roots); turnips (tops);
vegetables, fruiting; and wheat grain. Some of these commodities need
revisions with respect to commodity definitions to conform with the accepted
commodity names (see the Tolerance Reassessment Summary Table located
below for recommendations in revisions to commodity definitions) and some
are no longer regulated as significant feed items. The phrase "negligible
residue" [designated as "(N)"] will be administratively deleted from all entries
of 40 CFR ง180.205(a).
Tolerances for rice grain and rice straw of 0.05 and 0.06 ppm,
respectively, have recently been established (60 FR 7457, 2/8/95) in
conjunction with PP#5F03188. Tolerances for lentils and lentil forage and hay
of 0.3, 0.1, and 0.4 ppm, respectively, have recently been established (60 FR
27421, 5/24/95) in conjunction with PP#4E4359; lentil forage and hay are no
longer considered to be significant feed items and these tolerances will be
revoked.
Label revisions are required for paraquat dichloride uses on pastures and
rangelands in order to reflect the use patterns for which adequate residue data
are available. The individual tolerances for "grass, pasture" and "grass, range"
will be administratively revised to grass, forage at 90 ppm; and grass, hay at 40
ppm. A tolerance for pasture grass hay need not be proposed since this item is
not a recognized RAC (Table I of OPPTS 860.1000).
Label revisions are required for paraquat dichloride uses on alfalfa,
clover, and other legumes (including velvetbean, lespedeza, lupine, sainfoin,
trefoil, vetch, crown vetch, and milk vetch) in order to reflect the use patterns
for which adequate residue data are available. The individual tolerances for
"alfalfa", "birdsfoot trefoil", and "clover" will be redefined as non-grass animal
feeds group, forage at 75ppm and non-grass animal feeds group, hay at
210ppm. A tolerance for alfalfa meal need not be proposed since this item is
not a recognized RAC (Table I of OPPTS 860.1000).
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The ruminant feeding study is adequate to support the reassessment of
the following tolerances for milk and ruminant tissues: meat: 0.05 ppm; fat:
0.05 ppm, and liver (mybp): 0.05 ppm. However, the tolerance for ruminant
kidney will be raised from 0.3 to 0.5 ppm based on current data. Furthermore,
the commodity definitions will be revised to comply with Table I (of OPPTS
860.1000). While no tolerance would normally be considered necessary for
milk, in the interest of harmonization with CODEX, the Agency recommends
that the current 0.01 ppm tolerance be maintained. Also, all poultry and
poultry commodity tolerances except those for eggs will be revoked
[180.6(a)(3)]; in the interest of harmonization with CODEX, the current 0.01
ppm tolerance for eggs should remain.
The available field trial data indicate that the current tolerances for
"corn forage" and "corn fodder", each established at 0.05 ppm, will be
administratively increased. Furthermore, the commodity definitions will be
revised to reflect the respective corn types (i.e., field, sweet, and pop) in
compliance with Table I (of OPPTS 860.1000) commodity definitions. The
following tolerances will be administratively amended to distinguish the fodder
of various com types: corn, field, stover at 6 ppm; corn, pop, stover at 6 ppm;
and corn, sweet, stover at 6 ppin. Additionally, the following tolerances will be
administratively amended to distinguish the forage of various corn types: corn,
field, forage at 3 ppm; and corn, sweet, forage at 3 ppm. Due to the recent
Registration Division approval of use of paraquat dichloride as a harvest aid
(TN940007), the Agency required that additional field trials simulating this use
and a separate grain dust study be performed.
The established tolerance for soybeans will be administratively
increased from 0.05 ppm to 0.25 ppm. Additional data are required for
soybean grain dust to determine a specific numerical concentration factor; a
tolerance for aspirated grain fractions, as a RAC, may have to be proposed
pending the outcome of the required soybean grain dust study. The registrant
has expressed an intention to propose a lower tolerance for soybean forage at
0.03 ppm and to propose a tolerance for soybean hay at 0.05 ppm. Sufficient
data are available to support these proposed tolerance levels and will be
changed or established accordingly.
The available data indicate that the established tolerance for sorghum
forage is too low. The tolerance will be increased to 0.1 ppm for sorghum
forage. Label revisions are required to establish a 20-day PHI.
No tolerances currently exist for the following cereal grain
commodities: barley straw; popcorn grain; and wheat forage and straw.
Sufficient field residue data are available to determine appropriate tolerance
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levels for barley straw, wheat forage and straw, and popcorn grain. These
tolerances will be established at 1 ppm, 0.5 ppm, 1 ppm and O.OSppm
respectively.
No field residue data or a tolerance proposal for taro foliage have been
submitted. When the use of paraquat dichloride on taro was registered, Section
B of the petition included a restriction against the use of treated taro leaves for
food or feed purposes; however, this restriction is no longer permitted. The
registrant must submit field residue data and a tolerance proposal for residues
of paraquat dichloride in/on taro foliage.
The Agency now recognizes barley hay, cotton gin byproducts
(commonly called gin trash), and wheat hay as raw agricultural commodities
(Table I of OPPTS 860.1000). Residue data are now required for these
commodities, and appropriate tolerances should be proposed once acceptable
data have been submitted and evaluated. The required data for wheat hay will
be translated to barley hay.
Crop group tolerances of 0.05 ppm will be established for the members
of the Brassica (cole) leafy vegetables group and pome fruits group.
Established tolerances for broccoli; cabbage; cauliflower; Chinese cabbage;
collards will be combined under the Brassica group at the tolerance of 0.05
ppm. Established tolerances for apples and pears will be combined under the
pome fruit group at a tolerance of 0.05 ppm. Established tolerances for
apricots;, cherries; nectarines; peaches; and plums will be combined under the
stone fruits group at a tolerance of 0.05 ppm. Label revisions to establish a
maximum seasonal rate and a PHI are required for members of the stone fruits
group.
According to Table I (OPPTS 860.1000), the following items are no
longer recognized RACs, therefore, the established tolerances on these items
will be administratively revoked: fresh hops; hop vines; lentil hay; lentil
forage; bean straw; and peanut vines. In consideration of the designation of
dried hops as a RAC and not a processed food commodity, the entry in 40 CFR
ง185.4700 for dried hops will be transferred to 40 CFR ง180.205(a). In
addition, the available data indicate that the established tolerance for dried hops
is too low; the Agency will administratively increase the established tolerance
for dried hops, as a RAC, from 0.2 ppm to 0.5 ppm and redefined it as hops,
cone, dried. Additionally, the current tolerance for bean hay is being redefined
as cowpea, hay at 0.4 ppm and bean forage is being redefined as cowpea,
for age at 0.1 ppm.
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The established tolerance for "small fruit" will be amended to read
"berries". The present tolerances of 0.05, 0.05, and 0.25 ppm for grapes,
cranberries, and strawberries, respectively, will be considered under the
"Miscellaneous" grouping and listed individually.
The established tolerance for sugar beet tops will be lowered from 0.5
ppm to 0.05 ppm.
The established tolerances for oat grain and rye grain will be revoked
since there are presently no registered uses of paraquat on rye and the registrant
has indicated that they do not wish to support use of paraquat on oats.
A tolerance for corn, field, flour at 0.1 ppm will be established based on a
concentration factor of 1.5x in flour and the reassessed tolerance of 0.05 ppm
for the RAG.
The registrant should propose a tolerance for the processed commodities
of grapes.
A tolerance of 0.25 ppm will be established for paraquat residues in
pineapple processed residue based on a concentration factor of 4.5x in bran and
the reassessed tolerance of 0.05 ppm for the RAC.
Additionally, a tolerance for residues of paraquat in soybean hulls at 2
ppm will be established based on a concentration factor of 6.1x and the
reassessed tolerance of 0.25 ppm for the RAC.
Further, a tolerance of 3 ppm for residues of paraquat in sugarcane
molasses will be established based on a concentration factor of 5.5x in
blackstrap molasses and the reassessed tolerance of 0.5 ppm for the RAC.
Tolerances Listed Under 40 CFR ง180.205^: '
The tolerances listed in 40 CFR ง180.205(b) have been established with
regional registration and are expressed in terms of residues of paraquat derived
from application of either the bis (methyl sulfate) or the dichloride salt (both
calculated as a cation). A summary of paraquat tolerance reassessments is
presented in table form below.
Sufficient data are available to ascertain the adequacy of the established
tolerances for the following commodities, as defined in 40 CFR ง180.205(b):
cassava; pigeon peas; taniers; taro (conns); tyfon; and yams. Some of these
commodities need revisions with respect to commodity definitions to conform
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with the accepted commodity names; see the tolerance reassessment summary
table presented below for recommendations in revisions to commodity
definitions.
Tolerances Listed Under 40 CFR $185.4700:
Sufficient data are available to ascertain the adequacy of the established
tolerance in 40 CFR ง185.4700 for dried hops. The data indicate that the
established tolerance is too low. Since dried hops are now considered a RAC
and not a processed food item, the entry in 40 CFR ง185.4700 for dried hops
will be transferred to 40 CFR ง180.205(a) [see discussion above under
"Tolerances Listed Under 40 CFR ง180.205(a)"].
Tolerances Listed Under 40 CFR $186.4700:
Sufficient data are available to ascertain the adequacy of the established
tolerances in 40 CFR ง186.4700 for spent mint hay. However, Table I (OPPTS
860.1000) no longer specifies that data on spent mint hay are needed for
material balance, and a tolerance should not be set for this commodity.
Therefore, the existing tolerance for spent mint hay at 3 ppm should be
revoked. Additionally, Table II no longer specifies a tolerance is required for
sunflower seed hulls. Therefore, the existing tolerance for sunflower seed hulls
at 6 ppm should will be revoked.
Pending Tolerance Petitions:
The following petitions for the establishment of tolerances for residues
of paraquat in/on various commodities and applications for amended use
patterns are pending:
PP#5F01625/5H05088: The petition requests the registration of an
additional harvest-aid use for field corn and requests the following tolerances:
popcorn at 0.05 ppm; corn grain at 0.05 ppm; corn, fresh (inc. sweet) at 0.05
ppm; corn forage at 3.0 ppm; corn fodder at 10.0 ppm; and com flour at 0.1
ppm. This petition is currently in reject status because of several issues
including the need to submit a revised Section F and a full set of label
directions for popcorn.
PP#5F1639: The petition requests label use amendments for alfalfa,
clover, other legumes, and pasture and rangeland reseeding; the petition also
proposes revised tolerances for non-grass animal feeds group forage and hay,
alfalfa meal, and grass forage, fodder, and hay. This petition is currently in
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reject status because of several issues including the need for adequate field trial
data in support of petitioner-proposed changes in labeling.
PP#1E4019: The petition requests for the establishment of a tolerance
for artichokes. This petition is currently in reject status because additional field
trial data are required to support the proposed 1-day PHI.
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Tolerance Reassessment Summary for Paraquat Dichloride
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comment/
[Correct Commodity Definition]
Tolerances Listed Under 40 CFR 180.205(a):
Acerola
Alfalfa
Birdsfoot trefoil
Clover
Almond hulls
Apples
Pears
Apricots
Cherries
Nectarines
Peaches
Plums (fresh prunes)
Asparagus
Avocados
Bananas
Barley grain
Bean straw
Beans, dry
Beans, forage
Beans, hay
Beans, lima (succulent)
Beans, snap (succulent)
Beets, sugar
Beets, sugar (tops)
Broccoli
Cabbage
Cauliflower
Chinese cabbage
Collards
Cacao beans
Carrots
0.05
5
5
5
0.5
0.05(N)
0.05(N)
0.05(N)
0.05(N)
0.05(N)
0.05(N)
0.05(N)
0.5
0.05(N)
0.05(N)
0.05(N)
30.0
0.3
0.1
0.4
0.05
0.05
0.5
0.5
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
Will be replaced
with crop group
tolerances for
forage at 75 ppm
and hay at 210
ppm
0.5
..
0.5
0.05
0.05
0.05
Revoke
0.3
0.1
0.4
0.05
0.05
0.5
0.05
._
..
0.05
0.05
Crop group tolerance proposals must be made in conjunction
with required label revisions.
[Non-grass animal feeds group, forage ] and [Non-grass
animal feeds group, hay ]
[Almond, hulls}
A crop group tolerance of 0.05 ppm for [Pome fruits group ]
will be established.
Following the required label revisions, a crop group tolerance
of 0.05 ppm for the [Stone fruits group ] will be established.
[Barley, grain ]
[Beans, straw]
[Cowpea, forage ]
[Cowpea, hay]
[Beans, lima, succulent ]
[Beans, snap, succulent ]
[Sugar beets, roots ]
[Sugar beets, tops ] Residues were ND (O.025 ppm) on all
treated sugar beet top samples from field trials conducted at a
IX rate.
A crop group tolerance of 0.05 ppm for Brassica (cole) leafy
vegetables group will be established.
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Commodity
Cattle, fat
Cattle, kidney
Cattle, meat
Cattle, mbyp (except kidney)
Citrus fruit
Coffee beans
Corn, fresh (inc sweet com)
(K+CWHR)
Corn fodder
Corn forage
Com grain
Cottonseed
Cucurbits
Eggs
Figs
Goats, fat
Goats, kidney
Goats, meat
Goats, mbyp (except kidney)
Grass, pasture
Grass, range
Guar beans
Guava
Hogs, fat
Hogs, kidney
Hogs, meat
Hoss, mbvp (except kidney)
Current
Tolerance
(ppm)
0.05
0.3
0.05
0.05
0.05(N)
0.05(N)
0.05(N)
0.05(N)
0.05(N)
0.05(N)
0.5
0.05
0.01(N)
0.05(N)
0.05
0.3
0.05
0.05
5
5
0.5
0.05(N)
0.05
0.3
0.05
0.05
Tolerance
Reassessment
(ppm)
0.05
0.5
0.05
0.05
0.05
0.05
0.05
6
3
0.05
0.5
0.05
0.01
0.05
0.05
0.5
0.05
0.05
Will be replaced
with crop group
tolerances for
grass forage at
90 ppm and grass
hav at 40 ppm
0.5
0.05
0.05
0.5
0.05
0.05
Comment/
[Correct Commodity Definition]
CODEX Harmonization
[Citrus fruit group ]
[Coffee, bean, green ]
[Corn, sweet (K + CWHR) ]
The following tolerances will be established to distinguish the
fodder of various corn types:
[Corn, field, stover at 6 ppm],
[Corn, pop, stover at 6 ppm], and
[Corn, sweet, stover at 6 ppm].
The following tolerances will be established to distinguish the
forage of various corn types:
[Corn, field, forage at 3 ppm], and
[Corn, sv/eet, forage at 3 ppm].
Since paraquat use as a harvest aid in TN (TN940007) has
recently be approved, the Agency will require that additional
field trials be conducted by the registrant to support this use.
[Corn, field, grain }
[Cotton, seed]
[Cucurbit vegetables group ]
[Egg}
[Fig]
[Goat, fat]
CODEX Harmonization ; [Goat, kidney]
[Goat, meat]
[Goat.mbyp (except kidney)]
Crop group tolerance proposals must be made in conjunction
with required label revisions.
[Grass, forage},
and [Grass, hay}
[Guava}
[Hog, fat]
CODEX Harmonization ; [Hog, kidney]
[Hog, meat]
\Hos,mbvD (except kidney)!
104
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Commodity
Hops, fresh
Hop vines
Horses, fat
Horses, kidney
Horses, meat
Horses, mbyp (except kidney)
Kiwifruit
Lentils
Lentil, forage
Lentil, hay
Lettuce
Milk
Mint, hay
Nuts
Oat grain
Olives
Onions, dry bulb
Onions, green
Papayas
Passion fruit
Peanuts
Peanut, hay
Peanut, hulls
Peanut, vines
Peas (succulent)
Peas, forage
Peas, hay
Pineapples
Pistachio nuts
Potatoes
Poultry, fat
Current
Tolerance
(ppm)
0.1
0.5
0.05
0.3
0.05
0.05
0.05
0.3
0.1
0.4
0.05(N)
0.01(N)
0.5
0.05(N)
0.05(N)
0.05(N)
0.05
0.05
0.05(N)
0.2
0.05
0.5
0.2
0.5
0.05
0.2
0.8
0.05(N)
0.05
0.5
O.OKN)
Tolerance
Reassessment
(ppm)
. Revoke
Revoke
0.05
0.5
0.05
0.05
0.05
0.3
Revoke
Revoke
0.05
0.01
Revoke
0.05
Revoke
0.05
0.05
0.05
0.05
0.2
0.05
0.5
0.2
Revoke
0.05
0.2
0.8
0.05
0.05
0.5
Revoke
Comment/
[Correct Commodity Definition]
These items are not recognized RACs of hops (Table I, OPPTS
860.1000).
[Horse, fat]
CODEX Harmonization; [Horse, kidney]
[Horse, meat ]
[Horse, mbyp (except kidney)]
[Kiwifruit]
Recently established (60 FR 27421, 5/24/95) in conjunction
with PP#4E4359.
Recently established (60 FR 27421, 5/24/95) in conjunction
with PP#4E4359; however, this item is no longer recognized as
a RAC of lentils [Table I (OPPTS 860.1000)].
Recently established (60 FR 27421, 5/24/95) in conjunction
with PP#4E4359; however, this item is not a recognized RAC
of lentils [Table I (OPPTS 860.1000)].
[Peppermint, tops] [Spearmint, tops]
[Tree nuts group ]
Registrant has indicated that they do not wish to support use of
paraquat on oats.
[Olive]
[Onion, dry bulb (only) ]
[Onion, green]
[Papaya]
[Peanut, nutmeat]
[Peanut, hay]
[Peanut, hulls]
This item is not a recognized RAC of peanuts (Table I OPPTS
860.1000).
[Pea, succulent]
[Pea, field, vines]
[Pea, field, hay]
[Pineapple]
[Pistachio]
[Potato]
40CFR180.6(a)(3)
105
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Commodity
Poultry, meat
Poultry, mbyp
Rhubarb
Rice grain
Rice straw
Rye grain
Safflowcr seed
Sheep, fat
Sheep, kidney
Sheep, meat
Sheep, mbyp (except kidney)
Small fruit
Sorghum forage
Sorghum grain
Soybeans
Soybean forage
Strawberries
Sugarcane
Sunflower seeds
Turnips (roots)
Turnips (tops)
Vegetables, fruiting
Wheat grain
Current
Tolerance
(ppm)
0.01(N)
0.01(N)
0.05(N)
0.05
0.06
0.05(N)
0.05(N)
0.05
0.3
0.05
0.05
0.05(N)
0.05(N)
0.05(N)
0.05(N)
0.05CN)
0.25
0.5(N)
2
0.05
0.05
0.05
0.05(N)
Tolerance
Reassessment
(ppm)
Revoke
Revoke
0.05
0.05
0.06
Revoke
0.05
0.05
0.5
0.05
0.05
0.05
0.1
0.05
0.25
0.03
0.25
0.5
2
0.05
0.05
0.05
0.05
Comment/
[Correct Commodity Definition]
Recently established (60 FR 7457, 2/8/95) in conjunction with
PP#5F03188.
[Rice, grain]
Recently established (60 FR 7457, 2/8/95) in conjunction with
PP#5F03188.
[Rice, straw]
There are no registered uses of paraquat on rye.
[Safflower, seed]
CODEX Harmonization
[Berries group ] '
The reassessed tolerance is contingent on a required proposal to
establish a PHI of 20 days.
[Sorghum, grain, forage ]
The reassessed tolerance is contingent on a required proposal to
establish a PHI of 48 days.
[Sorghum, grain, grain ]
Available data indicate current tolerance is too low.
This tolerance is based on preemergence use. Restrictions exist
against the grazing or harvesting for hay following
postemergence or harvest aid use.
[Soybeans, forage ]
[Strawberry]
[Sunflower, seed]
[Turnip, roots]
[Turnip, tops]
[Vegetables, fruiting (exc. cucurbits) group ]
[Wheat, grain]
Tolerances That Will Be Established or Need To Be Proposed Under 40 CFBง180.205(a)
Aspirated Grain Fraction
Barley, hav
-
-
TBDa
TBD"
The tolerance will be based on the results from the higher of the
soybean and corn aspirated grain fraction study, which have
been required by the Agency.
106
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Commodity
Barley, straw
Corn, field, flour
Corn, pop, grain
Cotton, gin byproducts
Cranberry
Grape
Grape, juice
Pineapple, process residue
Raisins
Soybeans, hay
Soybeans, hull
Sugarcane, molasses
Taro foliage
Wheat, forage
Wheat, hay
Wheat, straw
Current
Tolerance
(ppm)
-
-
-
~
-
Tolerance
Reassessment
(ppm)
1
0.1
0.05
TBDa
0.05
0.05
TBDa
0.25
TBDa
0.05
2
3
TBDa
0.5
TBDa
1
Comment/
[Correct Commodity Definition]
Cranberry, grape and strawberry have been moved from the old
"Small Fruits and Berries" crop grouping to the
"Miscellaneous" crop grouping.
A restriction against the use of treated foliage for food purposes
is no longer permitted. Taro foliage is no longer considered to
be an animal feed item.
Tolerances Listed Under 40 CFR 180.205(b):
Cassava
Pigeon peas
Taniers
Taro (conns)
Tyfon
Yams
0.05
0.05
0.05
0.1
0.05
0.05
0.05
0.05
0.05
0.1
0.05
0.05
[Cassava (manioc) ]
[TanierJ
{Taro, corm]
[Yam]
Tolerances Listed Under 40 CFR 185.4700:
Dried hops
0.2
0.5
In consideration of the designation of dried hops as a RAC and
not a processed feed commodity, the entry in 40 CFR
ง185.4700 for dried hops will be transferred to 40 CFR
ง180.205(a).
[Hops, cones, dried]
Tolerances Listed Under 40 CFR 186.4700:
Mint, hay, spent
Sunflower; seed hulls
3.0
6.0
Revoke
Revoke
No longer listed as a Table I (8/96) feed item.
No longer listed in Table I.
107
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TBD = To be determined. Assessment or reassessment of tolerance(s) cannot be made at this time because additional data are
required.
a.
CODEX Harmonization
The Codex Alimentarius Commission has established several
maximum residue limits (MRLs) for paraquat residues in various
commodities (see Guide to Codex Maximum Limits For Pesticide
Residues, Part 2, FAO CX/PR, 4/91). The Codex and U.S. tolerance are
in harmony with respect to MRL/tolerance expression; both regulate the
parent paraquat only. A comparison of the Codex MRLs and the
corresponding reassessed U.S. tolerances is presented in the Table
below.
The following conclusions can be made regarding efforts to
harmonize the U.S. tolerances with the Codex MRLs with respect to
MRL/tolerance level:
Compatibility between U.S. tolerances and Codex MRLs exists
for eggs, passion fruit, sunflower seed, and vegetables [including
beans (succulent), Brassica (cole) leafy vegetables group,
carrots, cassava, corn (sweet), cucurbits, fruiting vegetables,
lettuce, onions (dry bulb and green), peas (succulent), pigeon
peas, turnips (roots and tops), and yams], milk and ruminant
tissue, and poultry eggs.
Incompatibilities of U.S. tolerances and Codex MRLs on the
following raw plant commodities remain because of differences
hi agricultural practices: cottonseed, dry hops, maize, olives,
potatoes, rice, sorghum, and dry soya bean.
No questions of compatibility exist with respect to commodities
where: (i) no Codex MRLs have been established but U.S.
tolerances exist; or (ii) Codex MRLs have been established but
U.S. tolerances do not exist.
Codex MRLs and applicable U.S. tolerances. Recommendations for compatibility are based on
conclusions following reassessment of U.S. tolerances (see the tolerance reassement summary table
above).
Codex
Commodity (As Defined)
Cattle, kidney
Conon seed
MRLftng/kg)'
0.5
0.2
U.S. Tolerance
(ppm)
0.5
0.5
Recommendation And Comments
Compatability exists.
108
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Codex
Cotton seed oil, edible
Edible offal of cattle, pig,
and sheep (except as
otherwise listed)
Egg
Hop, dry
Maize
Meat of cattle, pig, and
sheep
Milk
Olive
Passion fruit
Pig, kidney
Potato
Rice
Rice, polished
Sheep, kidney
Sorghum
Soya bean (dry)
Sunflower seed
Sunflower seed oil, crude
Sunflower seed oil, edible
Vegetables
0.05 (*)
0.05 (*)
0.01 (*)
0.2
0.1
0.05 (*)
0.01 (*)
1
0.2
0.5
0.2
10
0.5
0.5
0.5
0.1"
2
0.05 (*)
0.05 (*)
0.05 (*)
U.S. Tolerance
~
0.05
0.01
0.5
0.05
0.05
0.01
0.05
0.2
0.5
0.5
0.05
0.5
0.05
0.25
2
~
0.05
Compatability exists
Compatibility exists.
Compatability exists
Compatibility exists.
Compatability exists
Compatability exists
Compatibility exists.
Compatibility exists for many vegetables including beans (succulent),
Brassica (cole) leafy vegetables group, carrots, cassava, cucurbits,
fruiting vegetables, lettuce, onions (dry bulb and green), peas
(succulent), rhubarbs, turnips (roots and tops), and yams.
All paraquat dichloride MRLs arc final (CXL) except on soya bean (dry). Asterisk () signifies that the MRL was established at or abort the limit of detection.
A proposal to establish an MKL of 0.2 mg/kg for soya bean (dry) reached Step 6. However, during the 23rd Session of the CCPR (4/91), the Committee decided to withdraw the
proposal andtheCXLforsoyabean(dry)at0.1 mg/kg was retained.
3. Tolerance Revocations and Import Tolerances
As part of the Agency's reregistration eligibility decision for paraquat dichloride
several food/feed uses will be cancelled/voluntarily cancelled. Once a pesticide use is
no longer registered in the United States, the related pesticide residue tolerance and/or
food/feed additive regulation generally is no longer needed. It is the Agency's's policy
to propose revocation of a tolerance, and/or food/feed additive regulation, following the
deletion of a related food use from a registration, or following the cancellation of a
related food-use registration.
The Agency recognizes, however, that interested parties may want to retain a
tolerance and/or food/feed additive regulation in the absence of a U.S. registration, to
allow legal importation of food into the U.S. To assure that all food marketed in the
U.S. is safe, under FFDCA, the Agency requires the same technical chemistry and
toxicology data for such import tolerances (tolerances without related U.S. registrations)
as are required to support U.S. food use registrations and any resulting tolerances. See
40 CFR Part 158 for the Agency's data requirements to support domestic use of a
pesticide and establishment and maintenance of a tolerance and/or food/feed regulation.
109
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In. addition, the Agency requires residue chemistry data (crop field trials) that are
representative of growing conditions in exporting countries in the same manner that the
Agency requires representative residue chemistry data from different U.S. regions to
support domestic use of the pesticide and the tolerance and/or regulation. Additional
guidance on the Agency's import tolerance policy will be published in an upcoming
Federal Register Notice.
Parties interested in supporting an existing paraquat tolerance as an import tolerance
should ensure that all of the data noted above are available to the Agency during its
further assessments of existing tolerances and regulations, so that the Agency may
determine whether maintenance of the tolerance and/or regulation would be protective
of the public health.
4. Summary of Risk Management Decisions
a. Human Health
(1) Dietary
Acute Dietary
The Agency has determined that a risk assessment for acute dietary (1 day)
risk is not necessary, since no data presented/available suggest a need for an acute
dietary endpoint.
Chronic Dietary ("including cancer)
The Agency has evaluated the chronic dietary risk associated with the use of
paraquat based on established and proposed tolerance levels and assuming 100%
of each crop is treated. The RfD was established at 0.0045 mg/kg/day (expressed
as paraquat cation) based upon a chronic toxicity (1 year) study in dogs with a
NOEL of 15ppm (.45 mg/kg/day) and an uncertainty factor (UF) of 100. The
chronic dietary risk is considered to be minimal. The chronic exposure analysis
results in a TMRC where the RfD was not exceeded for any of the 22 populations
subgroups analyzed. The chronic dietary exposure using the existing tolerances
result hi a Theoretical Maximum Residue Contribution (TMRC) which is 10% of
the RfD for the U.S. general population. The subpopulation with the highest
exposure is non-nursing infants (<1 year old). This subpopulation's TMRC
utilizes 31% of the RfD. The Agency considers exposures which utilize 100% or
less of the RfD to be adequately protective.
(2) Worker (Mixer/Loader/Applicator)
110
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Acute (Short-Term) and Intermediate Term
The Toxicological Endpoint Selection Committee (TES) indicated
inhalation endpoints should be used for risk assessment only in cases in which the
spray particles are of a respirable size. This endpoint was based on the NOEL and
LOEL for subchronic (3 weeks) inhalation toxicity, for both sexes, of 0.01 ug/L
and 0.10 ug/L, respectively, expressed as paraquat cation. The Agency decided
that particles used in agricultural practices (400 to 800 um) are well beyond the
resipirable range and therefore there is no need for this endpoint.
The Agency has determined that there is a potential dermal exposure to
pesticide handlers. Therefore, for all other use scenarios (such as agricultural
applications), a "dermal endpoint" is used: NOEL of 3 mg/kg/day, expressed as
paraquat cation, based on maternal toxicity effects: unscheduled deaths, thin and
hunched appearance, decreased body weight gain, and histological changes in the
lungs and kidneys of the nonsurvivors. Exposure by the dermal route, obtained by
extrapolating data (NOEL) from a combination of two rat developmental toxicity
studies and correcting for dermal absorption (0.3%), is appropriate for short term
occupational and residential exposure. (MRIDs 00113714, 43964701 and
00153439). The rat developmental toxicity study was selected over the rabbit 21-
day dermal study because the Toxicology Endpoint Selection Committee (TES)
generally looks for systemic toxicity endpoints. The only biologically significant
endpoint observed in the 21-day dermal study was dermal irritation which is not
considered to be a systemic effect. Therefore, the NOEL for developmental
effects from the rat developmental toxicity study was selected as the endpoint of
choice.
The MOEs for short and intermediate-term occupational exposure dermal
effects to paraquat are greater than 100 for all the exposure scenarios considered
except for backpack sprayer for applicators and low pressure sprayer (resin
soaking) for mixer/loader/applicators. For applicators using the backpack sprayer
the MOE for dermal exposure is 31 and for the mixer/loader/applicator using the
low pressure sprayer (resin soaking) the MOE for dermal exposure is 36. These
MOES assume the use of long pants and long-sleeve shirts (no gloves). However,
with the addition of gloves, the MOE for backpack spayer is raised to 64 and the
MOE for the mixer/loader/applicator using the low pressure sprayer (resin
soaking) is raised to 910. Since the backpack spayer scenario MOE is still below
100, even with the addition of gloves, the Agency and the registrant have agreed
to the following requirements to mitigate (bring the unsatisfactory MOE up to 100)
the remaining risk:
111
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Modifying all paraquat labels to specify that the maximum backpack
applications (non-spot) be 0.625 cation/A with a minimum volume of 20
gallons per Acre.
This mitigation for backpack non-spot application reduces the finish
spray dilution concentration of paraquat in the spray tank to approximately
0.4% w/w of cation.
Post-Application
Based on the postapplication biological monitoring study the Agency has
determined that a 12 hour restricted-entry interval is adequate for the uses of
paraquat for preemergent or early-season weed control and weed control for
orchard and vegetable crops where the spray is directed solely at the weeds (not
broadcast over the entire crop area). A 24-hour restricted-entry interval is
required for desiccation and harvest aid applications of paraquat since the Agency
concludes such uses result in exposures to workers of a greater degree. These
12/24 hour post-application REI's measures should be sufficient to mitigate the
potential exposure to workers.
b. Environmental
(1) Avian
Acute
The Agency has evaluated data to determine the acute effects of paraquat
dichloride to birds. At the use rate of 1.49 Ibs cation/A the risk quotients were
determined to be more than 0.5, the LOG for presuming adverse effects to avian
species. At the proposed mitigation rate of 1.0 cation/A, restricted use and
endangered species LOCs will still be exceeded. However, because of the
environmental fate characteristics of paraquat, the risk to birds only exists shortly
after application. Once the applied paraquat has dried its risk is greatly reduced.
Therefore the Agency concludes the registered uses of paraquat dichloride are not
expected to pose significant acute risk to avian species.
Chronic
The Agency has evaluated data on the chronic effects of paraquat to birds.
The chronic risk quotients for birds range from 0.80 - 12.80 for the 1.6 Ib cation/A
rate and 0.5 - 8.00 for the 1.0 Ib cation/A rate. Normally these high LOCs would
indicate a chonic risk to birds. However, as noted above, the environmental fate
112
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data indicate that paraquat once applied and dried is not expected to pose a risk.
Therefore, the registered uses of paraquat dichloride are not expected to pose a
significant chronic risk to avian species.
Although a chronic risk is not expected, the Agency was concerned that
direct use of paraquat dichloride may affect avian reproduction. However, after
reviewing additional information regarding the uses of paraquat (Row Crop,
Tree/Vine/Fruit, Vegetable, Alfalfa, and Harvest-Aid uses) the Agency has
concluded that the greater risk to eggs within a treated field is from subsequent
agricultural practices such as mowing, bailing, fungicide and insecticide spraying,
irrigation, etc.. Regarding effects to off-field nesting areas, assuming 5% drift, the
resulting "in egg" concentrations of paraquat are not expected to be sufficient to
cause significant mortality or reductions in hatchability and growth.
(2) Mammals
Acute
Even though some of the risk quotients for paraquat dichloride exceed high
acute risk for the 1.6 Ib cation/A and 1.0 cation/A application rate, the Agency
concludes that the use of paraquat will not harm mammals, including endangered
species through acute toxicity since it becomes biologically unavailable once it
dries.
Chronic
The Agency has evaluated data to determine the chronic effects of paraquat
dichloride to mammals. At the use rate of 1.6 Ib cation/A and 1.0 Ib cation/A
some of the risk quotients were determined to be more than 1, the LOC for
presuming chronic risk to mammals. However, environmental fate data indicate
that paraquat once applied and dried is not expected to pose risk. Likewise, the
risk mitigation measures (reduced application rates) proposed above for birds
should also reduce the exposure of paraquat to mammals.
(3) Insects
Paraquat is practically non-toxic to honeybees and for the most part paraquat
will be used at times when honey bees will not be active in the field. Therefore,
the use of paraquat is not likely to affect honey bees.
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(4) Freshwater Fish
No acute or chronic LOCs have been exceeded for freshwater fish.
Therefore, the use of paraquat dichloride is not likely to adversely affect
freshwater fish.
(5) Aquatic invertebrates
No acute or chronic LOCs have been exceeded for freshwater invertebrates.
Therefore, the use of paraquat dichloride is not likely to adversely affect
freshwater invertebrates.
(6) Estuarine and Marine Organisms
No acute LOCs have been exceeded for estuarine and marine organisms.
Therefore, the use of paraquat dichloride is unlikely to adversely impact
estuarine/marine endangered or non-endangered species. Data were not available
to assess the chronic risk to estuarine and marine organisms. Due to paraquat
dichloride's strong adsorption to soil which makes it biologically unavailable,
chronic testing on estuarine and marine organisms is not required.
(7) Nontarget Plants (Terrestrial, Semi-Aquatic, and Aquatic)
The Agency has evaluated data which indicate that LOCs are exceeded for
terrestrial, and semi-aquatic plants. As was stated previously, paraquat dichloride
binds strongly to soil and it is therefore not expected to affect non-target terrestrial
and semi-aquatic plants as a result of runoff. Rather the risk of paraquat to non-
target terrestrial and semi-aquatic plants is expected to come only as a result of
drift during application. Depending on the application method and application
rates, the risk quotients for non-endangered terrestrial and semi-aquatic plants
range from 0.0 -6.15 and the endangered species risk quotients range from 0.0 -
20.0. Therefore, drift from paraquat may adversely affect nontarget terrestrial and
semi-aquatic plants, including endangered species.
At paraquat's lowest application rate of 0.07 Ib cation/A, no risk to
endangered terrestrial and semi-aquatic plants is expected. In order to mitigate the
upper end risk quotients, the registrant has agreed to lower the maximum use rate
to 1 Ib cation/A. However, aerial application of paraquat at the 1.0 Ib cation/A
rate is still expected to pose some risk to non-target terrestrial and semi-aquatic
plants due to drift, but ground application at the same rate is not expected to pose
risk.
114
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To provide additional protection to non-target terrestrial and semi-aquatic
plants the following mitigation measures are being required:
Aerial applications must include the most current spray drift language (see
description under Actions Required by Registrants)
All paraquat products must place a statement in the "Environmental
Hazard"section of the label that warns the user about possible adverse effects to
non-target and semi-aquatic plants due to drift. (See section V for the specific
labeling statement).
(8) Endangered Species
The Agency has concerns about the exposure of threatened and endangered
plant and animal species to paraquat as discussed above in the science assessment
chapter. Endangered species LOCs have been exceeded for chronic effects on
birds, small mammals and for acute effects on semi-aquatic and terrestrial plants.
The risk for birds and small mammals only exist until the paraquat dichloride
residues dries (or becomes bound).
Currently, the Agency is developing a program ("The Endangered Species
Protection Program") to identify all pesticides whose use may cause adverse
impacts on endangered and threatened species and to implement mitigation
measures that will eliminate the adverse impacts. The program would require use
restrictions to protect endangered and threatened species at the county level.
Consultations with the Fish and Wildlife Service may be necessary to assess risks
to newly listed species or from proposed new uses. In the future, the Agency
plans to publish a description of the Endangered Species Program in the Federal
Register and have available voluntary county-specific bulletins. Because the
Agency is taking this approach for protecting endangered and threatened species,
it is not imposing label modifications at this time through the RED. Rather, any
requirements for product use modifications will occur in the future under the
Endangered Species Protection Program;
(9) Water Resources
Although there were detections of paraquat in drinking water wells from two
states cited in the Pesticides in Groundwater Database, these detections are not
considered to be representative of normal paraquat use. Paraquat dichloride binds
so strongly to soil clay particles that it did not leach from the surface in the,
terrestrial field dissipation studies. Therefore, the Agency concludes there is no
concern for paraquat contaminating groundwater from normal use patterns.
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(10) Restricted Use Classification
All paraquat products are currently classified as pesticides (February 9,
1978, 43 FR 5782). Originally, this restriction was based on acute toxicity and the
potential for intentional or inadvertent exposure. More recent acute data indicate
lower toxicity for all routes of exposure except inhalation (a new inhalation study
was not submitted). However, the spray droplets of paraquat from all currently
registered products are not of respirable size and inhalation is not an exposure
route of concern. Notwithstanding the lack of acute toxicity concerns, the Agency
is maintaining the Restricted Use classification for all paraquat products based on
the severity of effects from paraquat oral ingestion and inappropriate dermal
exposure, limited effectiveness of therapeutic treatment after exposure and in
order to continue to deter misuse of this product.
5. Occupational/Residential Labeling Rationale
The Worker Protection Standard (WPS)
Scope of the WPS
The 1992 Worker Protection Standard for Agricultural Pesticides (WPS) established
certain worker-protection requirements (personal protective equipment, restricted-entry
intervals, etc.) to be specified on the label of all products that contain uses within the
scope of the WPS. Uses within the scope of the WPS include all commercial (non-
homeowner) and research uses on farms, forests, nurseries, and greenhouses to produce
agricultural plants (including food, feed, and fiber plants, trees, turf grass, flowers,
shrubs, ornamentals, and seedlings). Uses within scope include not only uses on plants,
but also uses on the soil or planting medium the plants are (or will be) grown in.
At this time some of the registered uses of paraquat are within the scope of the
Worker Protection Standard for Agricultural Pesticides (WPS) and some uses are
outside the scope of the WPS. Some examples of uses that are outside the scope of the
WPS include use:
" on pastures or rangelands,
on plants that are in ornamental gardens, parks, golf courses, and public or private
lawns and grounds and that are intended only for decorative or environmental
benefit.
in a manner not directly related to the production of agricultural plants, including,
for example, control of vegetation along rights-of-way and in other non-crop
areas.
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Compliance With the WPS
Any product whose labeling can be reasonably interpreted to permit use in the
production of an agricultural plant on any farm, forest, nursery, or greenhouse must
comply with the labeling requirements of PR Notice 93-7, "Labeling Revisions
Required by the Worker Protection Standard (WPS)," and PR Notice 93-11,
"Supplemental Guidance for PR Notice 93-7," which reflect the requirements of the
Agency's labeling regulations for worker protection statements (40 CFR part 156,
subpart K). These labeling revisions are necessary to implement the Worker Protection
Standard for Agricultural Pesticides (40 CFR part 170) and must be completed in
accordance with, and within the deadlines specified in, PR Notices 93-7 and 93-11.
Unless otherwise specifically directed in this RED, all .statements required by PR
Notices 93-7 and 93-11 are to be on the product label exactly as instructed in those
notices.
After April 21, 1994, except as otherwise provided in PR Notices 93-7 and 93-11,
the labeling of all products within the scope of those notices must meet the
requirements of the notices when the products are distributed or sold by the
primary registrant or any supplementally registered distributor.
After October 23,1995, except as otherwise provided in PR Notices 93-7 and
93-11, the labeling of all products within the scope of those notices must meet the
requirements of the notices when the products are distributed or sold by any
person.
Personal Protective Equipment/Engineering Controls for Handlers
For each end-use product, PPE requirements for pesticide handlers are set during
reregistration in one of two ways:
1. If the Agency determines that no regulatory action must be taken as the result of the
acute effects or other adverse effects of an active ingredient, the PPE for pesticide
handlers will be based on the acute toxicity of the end-use product. For occupational-
use products, PPE must be established using the process described in PR Notice 93-7 or
more recent EPA guidelines.
2. If the Agency determines that regulatory action on an active ingredient must be taken
as the result of very high acute toxicity or to certain other adverse effects, such as
allergic effects or delayed effects (cancer, developmental toxicity, reproductive effects,
etc.):
In the RED for that active ingredient, the Agency may establish minimum or
"baseline" handler PPE requirements that pertain to all or most end-use products
containing that active ingredient.
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* These minimum PPE requirements must be compared with the PPE that would be
designated on the basis of the acute toxicity of the end-use product.
" The more stringent choice for each type of PPE (i.e., body wear, hand protection,
footwear, eyewear, etc.) must be placed on the label of the end-use product.
Personal protective equipment requirements usually are set by specifying one or
more pre-established PPE units ~ sets of items that are almost always required together.
For example, if chemical-resistant gloves are required, then long-sleeve shirts, long
pants, socks, and shoes are assumed and are also included in the required minimum
attire. If the requirement is for two layers of body protection (coveralls over a long- or
short-sleeve shirt and long or short pants), the minimum must also include (for all
handlers) chemical-resistant footwear and chemical-resistant headgear for overhead
exposures and (for mixers, loaders, and persons cleaning equipment) chemical-resistant
aprons.
Occupational-Use Products
The Agency has determined that regulatory action regarding the establishment of
active-ingredient-based minimum PPE requirements for occupational handlers must be
taken for paraquat. Even though the MOE's were greater than 100 for occupational
mixers, loaders, and applicators (except backpack applicators and resin-soaking uses)
without personal protective equipment requirements beyond long-sleeve shirt, long
pants, shoes, and socks, the Agency notes the relatively significant epidemiological
evidence of poisonings from intentional/accidental oral ingestion and numerous non-
systemic skin and eye effects in California (see California Pesticide Illness Surveillance
System Data in OREB memo form J. Blondell, entitled: "Review of Paraquat Acute
Illness Data", 12/5/95). These considerations have led to the determination that active
ingredient-based minimum PPE should be required for all occupational paraquat
handlers.
Since potential handler exposure is similar for WPS and nonWPS uses, there is only
one set of active-ingredient-based minimum (baseline) PPE requirements for all
occupational uses of paraquat (specified in Section V). These requirements must be
followed in the labeling of all paraquat end-use products intended primarily for
occupational use.
Homeowner-Use Products
There are no registered homeowner-use products.
Post-Application/Entry Restrictions
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Occupational-Use Products (WPS Uses)
Restricted-Entry Interval:
Under the Worker Protection Standard (WPS), interim restricted-entry intervals
(REFs) for all uses within the scope of the WPS are based on the acute toxicity of the
active ingredient. The toxicity categories of the active ingredient for acute dermal
toxicity, eye irritation potential, and skin irritation potential are used to determine the
interim WPS REI. If one or more of the three acute toxicity effects are in toxicity
category I, the interim WPS REI is established at 48 hours. If none of the acute toxicity
effects are in category I, but one or more of the three is classified as category II, the
interim WPS REI is established at 24 hours. If none of the three acute toxicity effects
are in category I or II, the interim WPS REI is established at 12 hours. A 48-hour REI is
increased to 72 hours when an organophosphate pesticide is applied outdoors in arid
areas. In addition, the WPS specifically retains two types of REI's established by the
Agency prior to the promulgation of the WPS: (1) product-specific REI's established on
the basis of adequate data, and (2) interim REI's that are longer than those that would be
established under the WPS.
During the reregistration process, the Agency considers all relevant product-specific
information to decide whether there is reason to shorten or lengthen the previously
established REI.
During the reregistration process, the Agency determined that the restricted-entry
interval (REI) for all occupational-use products that contain paraquat and are within the
scope of the Worker Protection Standard for Agricultural Pesticides (WPS) should be
12 hours for preemergence and directed-spraying uses and 24 hours for desiccation and
harvesting uses.
Early-Entry PPE:
The WPS establishes very specific restrictions on entry by workers to areas that
remain under a restricted-entry interval, if the entry involves contact with treated
surfaces. Among those restrictions are a prohibition of routine entry to perform hand
labor tasks and a requirement that personal protective equipment be worn. Under the
WPS, these personal protective equipment requirements for persons who must enter
areas that remain under a restricted-entry interval are based on the acute toxicity
category of the active ingredient.
During the reregistration process, the Agency considers all relevant product-specific
information to decide whether there is reason to set personal protective equipment
requirements that differ from those set through the WPS.
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The RED requirements for early-entry personal protective equipment are set in one of
two ways:
1. If the Agency determines that no regulatory action must be taken as the result of
the acute effects or other adverse effects of an active ingredient, it establishes the
early-entry PPE requirements on the basis of the acute dermal toxicity category,
skin irritation potential category, and eye irritation potential category of the active
ingredient.
2. If theAgency determines that regulatory action on an active ingredient must be
taken as the result of very high acute toxicity or to certain other adverse effects,
such as allergic effects or delayed effects (cancer, developmental toxicity,
reproductive effects), it may establish early-entry PPE requirements that are more
stringent than would be established otherwise.
The Agency is establishing PPE for dermal protection on the basis of the acute
toxicity of the active ingredient. Paraquat is classified as toxicity category III for acute
dermal toxicity. Since paraquat is classified as category II for eye irritation potential,
protective eyewear is required.
WPS Notification Statement:
Under the WPS, the labels of some pesticide products must require employers to
notify workers about pesticide-treated areas orally as well as by posting of the treated
areas. The reregistration process also may decide that a product requires this type of
"double notification."
Based on the acute toxicity of the active ingredient, the Agency is not requiring
double notification.
Occupational-Use Products (NonWPS Uses)
Since the Agency has concerns about post-application exposures to persons after
nonWPS occupational uses of paraquat, it is establishing entry restrictions for all
nonWPS occupational uses of paraquat end-use products. For specific requirements,
refer to Section V of this document.
Homeowner-Use Products
There are no registered homeowner-use products.
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Other Labeling Requirements
The registrant has agreed to lower application rates and label changes for tree
injection. These changes are summarized in Section V. The Agency is also requiring
other use and safety information to be placed on the labeling of all end-use products
containing paraquat. For the specific labeling statements, refer to Section V of this
document.
V. ACTIONS REQUIRED OF REGISTRANTS
This section specifies the data requirements and responses necessary for the reregistration of
both manufacturing-use and end-use products.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregistration of paraquat dichloride for the
above eligible uses has been reviewed and determined to be substantially complete.
However, EPA is requiring data to establish tolerances for paraquat dichloride on taro
foliage, corn and soybean aspirated grain fractions, wheat and hay, cotton and gin
byproducts and processed grapes. The Agency is also requiring data to confirm that the
existing tolerance for field corn is adequate to cover the specialized use of paraquat as a
harvest aid. See the chart below for data requirements:
Guideline #
62-3
171-3
171-4(k)
171-4(k)
171-4(k)
171-4(k)
171-4(k)
171-4(1)
201-1
202-1
Study Title
Analytical Methods (For the MP, EPA Reg. No. 10182-362)
Directions for Use
Magnitude of the Residue
Mag. of the Res. in Plants
Mag. of the Res. in Plants
fractions
Mag. of the Res. in Plants
Mag. of the Res. in Plants
in Plants - Taro foliage
- Soybean aspirated grain fractions
- Corn, field, grain and aspirated grain
- Wheat and hay*
- Cotton, and gin byproducts
Mag. of the Res in Processed Food/Feed - Grapes
Droplet size spectrum
Drift field evaluation
* The registrant should refer to the 4/23/96 CBRS memorandum and cite the available data for wheat
straw.
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2. Labeling Requirements for Manufacturing-Use Products
To remain in complaince with FIFRA, manufacturing use product (MP) labeling
must be revised to comply with all current EPA regulations, PR Notices and applicable
policies. The MP labeling must bear the following statement under Directions for Use:
"Only for formulation into an
_[fill blank with Insecticide, Herbicide or
the applicable term which describes the type of pesticide use(s)] for the following
use(s) [fill blank only with those uses that are being supported by MP
registrant."
An MP registrant may, at his/her discretion, add one of the following statements to an
MP label under
"Directions for Use" to permit the reformulation of the product for a specific use
or all additional uses supported by a formulator or user group:
(a) "This product may be used to formulate products for specific use(s) not listed
on the MP label if the formulator, user group, or grower has complied with
U.S. EPA submission requirements regarding support of such use(s)."
(b) "This product may be used to formulate products for any additional use(s) not
listed on the MP label if the formulator, user group, or grower has complied
with U.S. EPA submission requirements regarding support of such use(s)."
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-
specific data regarding the pesticide after a determination of eligibility has been made.
The product specific data requirements are listed in Appendix G, the Product Specific
Data Call-in Notice.
Registrants must review previous data submissions to ensure that they meet current
EPA acceptance criteria (Appendix F; Attachment E) and if not, commit to conduct new
studies. If a registrant believes that previously submitted data meet current testing
standards, then study MRID numbers should be cited according to the instructions in the
Requirement Status and Registrants Response Form provided for each product.
2. Labeling Requirements for End-Use Products
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a. Application Rates and Label Deletions
In cooperation with the Agency the registrant has agreed to the following
application rates and label deletions:
O The maximum paraquat dichloride application rate for all products will be
lowered from 1.6 Ib cation/A to 1.0 Ib cation/A.
For broadcast applications of paraquat with backpack sprayers, non-spot, the
application rate should not exceed 0.625 Ib cation/A and the application volume
should be no less than 20 gallons per acre.
The maximum application rate for spot spraying on all paraquat labels will be
no more than 0.0195 Ibs cation/gallon.
O Delete the plastic acid bottle and the tree injection directions for use from the
resin soaking sections of all paraquat dichloride labels.
b. Hazard Statement
The following hazard statement must be placed in the "Environmental Hazard"
section of all paraquat labels to warn the user about possible adverse effects to non-
target terrestrial and semi-aquatic plants due to drift:
"Paraquat dichloride is toxic to nontarget crops and plants if off-target
movement occurs. Extreme care must be taken to ensure that off-target drift
is minimized to the greatest extent possible."
c. PPE/Engineering Control Requirements for Pesticide Handlers
For sole-active-ingredient end-use products that contain paraquat, the product
labeling must be revised to adopt the handler personal protective
equipment/engineering control requirements set forth in this section. Any conflicting
PPE requirements on the current labeling must be removed.
For multiple-active-ingredient end-use products that contain paraquat, the
handler personal protective equipment/engineering control requirements set forth in
this section must be compared to the requirements on the current labeling and the
more protective must be retained. For guidance on which requirements are
considered more protective, see PR Notice 93-7.
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d. Products Intended Primarily for Occupational Use (WPS and nonWPS)
Minimum (Baseline) PPE/Engineering Control Requirements
Although the MOE's were greater than 100 for all but two scenarios (backpack
applicators and resin-soaking uses) without personal protective equipment
requirements beyond long-sleeve shirt, long pants, shoes and socks, the Agency
notes the relatively significant epidemic logical evidence of poisonings from
intentional/accidental swallowing and numerous non-systemic skin and eye effects in
California (see OREB J. Blondell memo, 12/5/95). These considerations have led to
the Agency establishing the following minimum (baseline) PPE for all occupational
uses of paraquat end-use products:
"Mixers and loaders must wear:
long-sleeved shirt and long pants,
chemical-resistant gloves*,
shoes plus socks,
chemical-resistant apron,
face shield"
Although there is no direct evidence that occupational handlers have ever ingested
a lethal amount of paraquat from a splash or spill, the requirement for a face shield
for all mixers and loaders reflects the Agency's particular concern about accidental
swallowing in case of a spill or splash back.
"Applicators and other handlers (other than mixers and loaders) must wear:
-long-sleeved shirt and long pants,
chemical-resistant gloves*,
shoes plus socks"
* For the glove statement, use the statement established for paraquat through the
instructions in Supplement Three of PR Notice 93-7.
Determining PPE Requirements for End-use Product Labels
The PPE that would be established on the basis of the acute toxicity category of
the end-use product must be compared to the active-ingredient-based minimum
(baseline) personal protective equipment specified above. The more protective PPE
must be placed on the product labeling. For guidance on which PPE is considered
more protective, see PR Notice 93-7.
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Placement in Labeling
The personal protective equipment requirements must be placed on the end-use
product labeling in the location specified in PR Notice 93-7, and the format and
language of the PPE requirements must be the same as is specified in PR Notice 93-
7.
Products Intended Primarily for Occupational Use
There are no registered homeowner-use products
Entry Restrictions
For sole-active-ingredient end-use products that contain paraquat the product
labeling must be revised to adopt the entry restrictions set forth in this section. Any
conflicting entry restrictions on the current labeling must be removed.
For multiple-active-ingredient end-use products that contain paraquat the entry
restrictions set forth in this section must be compared to the entry restrictions on the
current labeling and the more protective must be retained. A specific time period in
hours or days is considered more protective than "sprays have dried" or "dusts have
settled."
e. Products Intended Primarily for Occupational Use - Entry Restrictions and
Labeling
WPS Uses
Restricted-entry interval:
"For preplant or preemergence (broadcast or banded) applications, post-
emergence directed-spray applications, dormant-season applications, and
"between cutting" alfalfa applications: Do not enter or allow worker entry into
treated areas during the restricted entry interval (REI) of 12 hours."
"For harvest-aid and desiccation applications: Do not enter or allow worker entry
into treated areas during the restricted entry interval (REI) of 24 hours."
Early-entry personal protective equipment (PPE):
The PPE required for early entry is:
coveralls,
chemical-resistant gloves*,
shoes plus socks,
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protective eyewear.
* For the glove statement, use the statement established for paraquat through the
instructions in Supplement Three of PR Notice 93-7.
WPS Notification Statement;
Not reqiured on label.
Placement in labeling:
The REI statements must be inserted into the Agricultural Use Requirements box as
required by Supplement Three of PR Notice 93-7. The PPE required for early entry
must be inserted into the standardized early-entry PPE statement required by
Supplement Three of PR Notice 93-7. The double notification statement must be
placed into the Agricultural Use Requirements box as required by Supplement Three
of PR Notice 93-7.
NonWPS uses
Entry restrictions:
The Agency is establishing the following entry restrictions for nonWPS
occupational uses of paraquat end-use products:
"Do not enter or allow others to enter the treated area until sprays have dried."
Placement in labeling:
If WPS uses are also on label - Follow the instructions in PR Notice 93-7 for
establishing a Non-Agricultural Use Requirements box, and place the appropriate
nonWPS entry restrictions in that box.
If no WPS uses are on the label Place the appropriate nonWPS entry restrictions
in the Directions for Use, under the heading "Entry Restrictions."
Products Intended Primarily for Homeowner Use
Entry restrictions:
There are no registered homeowner-use products.
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f. Other Labeling Requirements
Products Intended Primarily for Occupational Use
The Agency is requiring the following labeling statements to be located on all
end-use products containing paraquat that are intended primarily for occupational
use.
Application Restrictions
"Do not apply this product in a way that will contact workers or other
persons, either directly or through drift. Only protected handlers may be in
the area during application."
Engineering Controls
"When handlers use closed systems, enclosed cabs, or aircraft in a manner
that meets the requirements listed in the Worker Protection Standard (WPS)
for agricultural pesticides (40 CFR 170.240(d)(4-6), the handler PPE
requirements may be reduced or modified as specified in the WPS."
User Safety Requirements
"Discard clothing or other absorbent materials that have been drenched or heavily
contaminated with this product's concentrate. Do not reuse them."
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such
instructions for washable, use detergent and hot water. Keep and wash PPE
separately from other laundry."
"DO NOT USE AROUND HOMES, SCHOOLS, RECREATIONAL PARKS,
GOLF COURSES, OR PLAYGROUNDS"
User Safety Recommendations
"Users should wash hands before eating, drinking, chewing gum, using
tobacco, or using the toilet."
"Users should remove clothing immediately if pesticide gets inside. Then
wash thoroughly and put on clean clothing."
127
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ซ "Users should remove PPE immediately after handling this product. Wash
the outside of gloves before removing. As soon as possible, wash thoroughly
and change into clean clothing."
C. Spray Drift Labeling
The following language must be placed on each paraquat product label that can be
applied aerially:
Avoiding spray drift at the application site is the responsibility of the applicator. The
interaction of many equipment-and-weather-related factors determine the potential
for spray drift. The applicator and the grower are responsible for considering all
these factors when making decisions.
The following drift management requirements must be followed to avoid off-target
drift movement from aerial applications to agricultural field crops. These
requirements do not apply to forestry applications, public health uses or to
applications using dry formulations.
1. The distance of the outer most nozzles on the boom must not exceed 3/4 the
length of the wingspan or rotor.
2. Nozzles must always point backward parallel with the air stream and never be
pointed downwards more than 45 degrees.
Where states have more stringent regulations, they shall be observed.
The applicator should be familiar with and take into account the information covered
in the Aerial Drift Reduction Advisory Information.
The following aerial drift reduction advisory information must be contained in the
product labeling:
[This section is advisory in nature and does not supersede the mandatory label
requirements.]
INFORMATION ON DROPLET SIZE
The most effective way to reduce drift potential is to apply large droplets. The best
drift management strategy is to apply the largest droplets that provide sufficient
coverage and control. Applying larger droplets reduces drift potential, but will not
prevent drift if applications are made improperly, or under unfavorable
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environmental conditions (see Wind, Temperature and Humidity, and Temperature
Inversions).
CONTROLLING DROPLET SIZE
Volume - Use high flow rate nozzles to apply the highest practical spray volume.
Nozzles with higher rated flows produce larger droplets.
Pressure - Do not exceed the nozzle manufacturer's recommended pressures. For
many nozzle types lower pressure produces larger droplets. When higher flow rates
are needed, use higher flow rate nozzles instead of increasing pressure.
Number of nozzles - Use the minimum number of nozzles that provide uniform
coverage.
Nozzle Orientation - Orienting nozzles so that the spray is released parallel to the
airstream produces larger droplets than other orientations and is the recommended
practice. Significant deflection from horizontal will reduce droplet size and increase
drift potential.
Nozzle Type - Use a nozzle type that is designed for the intended application.
With most nozzle types, narrower spray angles produce larger droplets. Consider
using low-drift nozzles. Solid stream nozzles oriented straight back produce the
largest droplets and the lowest drift.
BOOM LENGTH
For some use patternSj reducing the effective boom length to less than 3/4 of the
wingspan or rotor length may further reduce drift without reducing swath width.
APPLICATION HEIGHT
Applications should not be made at a height greater than 10 feet above the top of the
largest plants unless a greater height is required for aircraft safety. Making
applications at the lowest height that is safe reduces exposure of droplets to
evaporation and wind.
SWATH ADJUSTMENT
When applications are made with a crosswind, the swath will be displaced
downwind. Therefore, on the up and downwind edges of the field, the applicator
must compensate for this displacement by adjusting the path of the aircraft upwind.
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Swath adjustment distance should increase, with increasing drift potential (higher
wind, smaller drops, etc.)
WIND
Drift potential is lowest between wind speeds of 2-10 mph. However, many factors,
including droplet size and equipment type determine drift potential at any given
speed. Application should be avoided below 2 mph due to variable wind direction
and high inversion potential. NOTE: Local terrain can influence wind patterns.
Every applicator should be familiar with local wind patterns and how they affect
spray drift.
TEMPERATURE AND HUMIDITY
When making applications in low relative humidity, set up equipment to produce
larger droplets to compensate for evaporation. Droplet evaporation is most severe
when conditions are both hot and dry.
TEMPERATURE INVERSIONS
Applications should not occur during a temperature inversion because drift potential
is high. Temperature inversions restrict vertical air mixing, which causes small
suspended droplets to remain in a concentrated cloud. This cloud can move in
unpredictable directions due to the light variable winds common during inversions.
Temperature inversions are characterized by increasing temperatures with altitude
and are common on nights with limited cloud cover and light to no wind. They begin
to form as the sun sets and often continue into the morning. Their presence can be
indicated by ground fog; however, if fog is not present, inversions can also be
identified by the movement of smoke from a ground source or an aircraft smoke
generator. Smoke that layers and moves laterally in a concentrated cloud (under low
wind conditions) indicates an inversion, while smoke that moves upward and rapidly
dissipates indicates good vertical air mixing.
SENSITIVE AREAS
The pesticide should only be applied when the potential for drift to adjacent sensitive
areas (e.g. residential areas, bodies of water, known habitat for threatened or
endangered species, non-target crops) is minimal (e.g. when wind is blowing away
from the sensitive areas).
D. Existing Stocks
130
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Registrants may generally distribute and sell products bearing old labels/labeling for 26
months from the date of the issuance of this Reregistration Eligibility Decision (RED).
Persons other than the registrant may generally distribute or sell such products for 50
months from the date of the issuance of this RED. However, existing stocks time frames
will be established case-by-case, depending on the number of products involved, the
number of label changes, and other factors. Refer to "Existing Stocks of Pesticide
Products; Statement of Policy"; Federal Register. Volume 56, No. 123, June 26, 1991.
The Agency has determined that registrants may distribute and sell paraquat dichloride
products bearing old labels/labeling for 26 months from the date of issuance of this RED.
Persons other than the registrant may distribute or sell such products for 50 months from
the date of the issuance of this RED. Registrants and persons other than registrants remain
obligated to meet pre-existing Agency imposed label changes and existing stocks
requirements applicable to products they sell or distribute.
131
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VI. APPENDICES
133
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APPENDIX A. Table of Use Patterns Subject to Reregistration
Appendix A is 213 pages long and is not being included. Copies of Appendix A are available upon request per
the instructions in Appendix E
135
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GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for active
ingredients within the case Paraquat Dichloride covered by this Reregistration Eligibility
Decision Document. It contains generic data requirements that apply to Paraquat Dichloride in
all products, including data requirements for which a "typical formulation" is the test
substance.
The data table is organized in the following format:
1. Data Requirement (Column 1). The data requirements are listed in the order in which
they appear in 40 CFR Part 158. the reference numbers accompanying each test refer to the
test protocols set in the Pesticide Assessment Guidelines, which are available from the
National Technical Information Service, 5285 Port Royal Road, Springfield, VA 22161 (703)
487-4650.
2. Use Pattern (Column 2). This column indicates the use patterns for which the data
requirements apply. The following letter designations are used for the given use patterns:
A Terrestrial food
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
O Indoor residential
3. Bibliographic citation (Column 3). If the Agency has acceptable data in its files, this
column lists the identifying number of each study. This normally is the Master Record
Identification (MRID) number, but may be a "GS" number if no MRID number has been
assigned. Refer to the Bibliography appendix for a complete citation of the study.
136
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GUIDE TO APPENDIX C
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated elsewhere in
the Reregistration Eligibility Document. Primary sources for studies in this bibliography
have been the body of data submitted to EPA and its predecessor agencies in support of
past regulatory decisions. Selections from other sources including the published literature,
in those instances where they have been considered, are included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study". In the case
of published materials, this corresponds closely to an article. In the case of unpublished
materials submitted to the Agency, the Agency has sought to identify documents at a level
parallel to the published article from within the typically larger volumes in which they
were submitted. The resulting "studies" generally have a distinct title (or at least a single
subject), can stand alone for purposes of review and can be described with a conventional
bibliographic citation. The Agency has also attempted to unite basic documents and
commentaries upon them, treating them as a single study.
3, IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted numerically
by Master Record Identifier, or "MRID number". This number is unique to the citation,
and should be used whenever a specific reference is required. It is not related to the six-
digit "Accession Number" which has been used to identify volumes of submitted studies
(see paragraph 4(d)(4) below for further explanation). In a few cases, entries added to the
bibliography late in the review may be preceded by a nine character temporary identifier.
These entries are listed after all MRID entries. This temporary identifying number is also
to be used whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry
consists of a citation containing standard elements followed, in the case of material
submitted to EPA, by a description of the earliest known submission. Bibliographic
conventions used reflect the standard of the American National Standards Institute (ANSI),
expanded to provide for certain special needs.
a Author. Whenever the author could confidently be identified, the Agency has chosen to
show a personal author. When no individual was identified, the Agency has shown an
identifiable laboratory or testing facility as the author. When no author or laboratory
could be identified, the Agency has shown the first submitter as the author.
b. Document date. The date of the study is taken directly from the document. When the
date is followed by a question mark, the bibliographer has deduced the date from the
evidence contained in the document. When the date appears as (19??), the Agency was
unable to determine or estimate the date of the document.
c. Title. In some cases, it has been necessary for the Agency bibliographers to create or
enhance a document title. Any such editorial insertions are contained between square
brackets.
155
-------
d. Trailing parentheses. For studies submitted to the Agency in the past, the trailing
parentheses include (in addition to any self-explanatory text) the following elements
describing the earliest known submission:
(1) Submission date. The date of the earliest known submission appears immediately
following the word "received."
(2) Administrative number. The next element immediately following the word
"under" is the registration number, experimental use permit number, petition
number, or other administrative number associated with the earliest known
submission.
(3) Submitter. The third element is the submitter. When authorship is defaulted to
the submitter, this element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the trailing
parentheses identifies the EPA accession number of the volume in which the
original submission of the study appears. The six-digit accession number follows
the symbol "CDL," which stands for "Company Data Library." This accession
number is in turn followed by an alphabetic suffix which shows the relative
position of the study within the volume.
156
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BIBLIOGRAPHY
MRID
CITATION
Memo dated 9/26/95, entitled "Paraquat dichloride formulated as Starfire
Herbicide or Gramaxone Extra ~ Worker Exposure Studies" from Krystyna
K. Locke, Toxicology Branch I, to Mary Clock, RCAB.
ORES memo entitled "Review of Paraquat Acute Illness Data" from Jerome
Blondell, Ph.D. Health Statistician, to Christiana Manville.
Gunther, Francis A., Ed. Residue Reviews. Residues of Pesticides and
Other Foreign Chemicals in Foods and Feeds. Springeer-Verlag, New York
Inc.: 1968, Vol. 23, p. 97.
Summers, L.A. Bipyridium Herbicides. Academic Press: 1980.
Blondell JM. 1994. Memorandum to Joshua First. Review of Poison
Control Center Data Call In. December 5, 1994. U.S. Environmental
Protection Agency, Washington, DC.
California Department of Food and Agriculture. 1983-1989. Pesticide Use
Report Annual (for years 1982-1988). Sacramento, California.
California Department of Pesticide Regulation. 1995. Case Reports
Received by the California Pesticide Illness Surveillance Program in Which
Health Effects Were Attributed to Exposure to Paraquat, Alone or In
Combination, 1982-1992.
Gamier R, Chataigner D, Efthymiou M-L, Morallon I, Bramaty F. 1994.
Paraquat poisoning by skin absorption: report of two cases. Veterinary and
Human Toxicology 36313-16.
GianessiLP. A National Pesticide Usage Data Base. 1986. Resources for
the Future, Washington, DC.
Keefe TJ, Savage EP, Wheeler HW. 1990. Third National Study of
Hospitalized Pesticide Poisonings in the United States, 1977-1982.
Epidemiologic Studies Center, Colorado State University, Fort Collins,
Colorado.
Litovitz TL, Schmitz BF, Bailey KM. 1990. 1989 Annual report of the
American Association of Poison Control Centers National Data Collection
System. American Journal of Emergency Medicine 8:394-442.
157
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BIBLIOGRAPHY
MRID
CITATION
GS0262-006
GS0262028
Litovitz TL, Bailey KM, Schmitz BF, et al. 1991. 1990 Annual report of the
American Association of Poison Control Centers National Data Collection
System. American Journal of Emergency Medicine 9:461-509.
Litovitz TL, Holm KC, Bailey KM, et al. 1992. 1991 Annual report of the
American Association of Poison Control Centers National Data Collection
System. American Journal of Emergency Medicine 10:452-505.
Litovitz TL, Holm KC, Clancy C, et al. 1993. 1992 Annual report of the
American Association of Poison Control Centers Toxic Exposure
Surveillance System. American Journal of Emergency Medicine 11:494-555
Litovitz TL, Clark LR, Soloway RA. 1994. 1993 Annual report of the
American Association of Poison Control Centers Toxic Exposure
Surveillance System. American Journal of Emergency Medicine 12:546-584
Morgan DP. 1989. Recognition and Management of Pesticide Poisonings.
U.S. Environmental Protection Agency, Washington, DC.
National Center for Health Statistics. 1983-1993. Vital Statistics of the
United States (for the years 1980-1989) Volume II, Part A. Public Health
Service, U.S. Government Printing Office, Washington, DC.
Smith JG. 1988. Paraquat poisoning by skin absorption: a review. Human
Toxicology 7:15-19.
Stevens JT and SumnerDD. 1991. Herbicides. Chapter 20 (pp. 1356-76) in
Handbook of Pesticide Toxicology, Volume 3. Edited by WJ Hayes and ER
Laws. Academic Press, San Diego.
Tinoco R, Tinoco R, Parsonnet J, Halperin D. 1993. Paraquat poisoning in
southern Mexico: a report of 25 cases. Archives of Environmental Health
48:78-80.
Chevron Chemical Co. (1966) Residue Data Sheet: Avocados: Paraquat:
Test No. T-1020. (Unpublished study prepared by Diablo Laborities, Inc.
4p.
US EPA (1979) 48-Hour EC50: Paraquat dichloride 29.1%: Daphnia
Magna: Test 2431. Unpublished report prepared by Terrestrial Aquatic
Biology Laboratory. 1 p.
158
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BIBLIOGRAPHY
MRID
CITATION
00015751 Rose, W.; Worsham, D.; Slagowski, J.L. (1978) Metolachlor (Dualฎ 8E);
Atrazine (AAtrexฎ SOW); Paraquat (Paraquat CL): AG-A No. 4959 1,11.
(Unpublished study received Mar 16, 1979 under 100-583; prepared in
cooperation with EN-CAS Laboratories and Chevron Chemical Co.,
submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:237819-F)
00015752 Kern, C.L.; Staniforth, D.; Slagowski, J.L. (1978) Metolachlor (Dualฎ 8E);
Atrazine (AAtrexฎ SOW or 4L); Paraquat (Paraquat CL): AG-A No. 5000
1,11. (Unpublished study received Mar 16, 1979 under 100-583; prepared in
cooperation with Iowa State Univ., EN-CAS Laboratories and Chevron
Chemical Co., submitted by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:237819-H)
00015768 Kincaid, L.; Slagowski, J.L. (1978) Metolachlor + Liriuron + Paraquat; Dual
8E + Lorox SOW + Paraquat 2CL: AG-A No. 4762 1,11. (Unpublished study
including letter dated May 23, 1978 from J.D. Riggleman to Robert A.
Kahrs, received Mar 16, 1979 under 100-583; prepared in cooperation with
Chevron Chemical Co. and E.I. du Pont de Nemours & Co., Inc., submitted
by Ciba-Geigy Corp., Greensboro, N.C.; CDL:237821-J)
00015769 Searcy, V.; Herman, D.; Slagowski, J.L. (1978) Metolachlor + Linuron +
Paraquat: Dual 8E + Lorox SOW + Paraquat 2CL: AG-A No. 4892 1,11.
(Unpublished study including letter dated May 23, 1978 from J.D.
Riggleman to Robert A. Kahrs, received Mar 16,1979 under 100-583;
prepared in cooperation with Chevron Chemical Co. and E.I. du Pont de
Nemours & Co., Inc., submitted by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:237821-L)
00015770 Schnappinger, M.G.; Slagowski, J.L. (1978) Metolachlor + Linuron +
Paraquat (Dual 8E + Lorox SOW + Paraquat 2CL): AG-A No. 4915 I, II.
(Unpublished study including letter dated May 23, 1978 from J.D.
Riggleman to Robert A. Kahrs, received Mar 16, 1979 under 100-583;
prepared in cooperation with Chevron Chemical Co. and E.I. du Pont de
Nemours & Co., Inc., submitted by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:237821-L)
00015771 Rose, W.; Worsham, D.; Slagowski, J.L. (1978) Metolachlor + Linuron +
Paraquat: Dualฎ 8E + Lorox SOW + Paraquat 2CL: AG-A No. 4955 1,11.
(Unpublished study including letter dated May 23, 1978 from J.D.
Riggleman to Robert A. Kahrs, received Mar 16, 1979 under 100-583;
prepared in cooperation with Rocky Mount Experiment Station, Chevron
Chemical Co. and E.I. du Pont de Nemours & Co., Inc., submitted by
Ciba-Geigy Corp., Greensboro,
159
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BIBLIOGRAPHY
MRID
CITATION
00015772 Kincaid, L.; Slagowski, J.L. (1978) Metolachlor (Dualฎ 8E); Metribuzin
(Sencor SOW); Paraquat (2C1): AG-A No. 47641,11. (Unpublished study
including letter dated May 23, 1978 from J.D. Riggleman to Robert A.
Kahrs, received Mar 16, 1979 under 100-583; prepared in cooperation with
E.I. du Pont de Nemours & Co., Inc. and Chevron Chemical Co., submitted
by Ciba-Geigy Corp., Greensboro, N.C.; CDL:237821-M)
00015773 Searcy, S.; Herman, D.; Slagowski, J.L. (1978) Metolachlor (Dualฎ 8E);
Metribuzin (Sencor SOW); Paraquat (2C1): AG-A No. 48941,11.
(Unpublished study including letter dated May 23, 1978 from J.D.
Riggleman to Robert A. Kahrs, received Mar 16, 1979 under 100-583;
prepared in cooperation with E.I. du Pont de Nemours & Co., Inc. and
Chevron Chemical Co., submitted by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:237821-O)
00015774 Schnappinger, M.G.; Slagowski, J.L. (1978) Metolachlor (Dualฎ 8E);
Metribuzin (Sencor SOW); Paraquat (2 Cl): AG-A No. 4916 I, II.
(Unpublished study including letter dated May 23, 1978 from J.D.
Riggleman to Robert A. Kahrs, received Mar 16, 1979 under 100-583;
prepared in cooperation with E.I. du Pont de Nemours & Co., Inc. and
Chevron Chemical Co., submitted by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:237821-P)
00015775 Rose, W.; Worsham, D.; Slagowski, J.L. (1978) Metolachlor (Dualฎ 8E);
Metribuzin (Sencor SOW); Paraquat (Cl): AG-A No. 49571,11.
(Unpublished study including letter dated May 23, 1978 from J.D.
Riggleman to Robert A. Kahrs, received Mar 16, 1979 under 100-583;
prepared in cooperation with E.I. du Pont de Nemours & Co., Inc. and
Chevron Chemical Co., submitted by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:237821-Q)
00015955 Luke, J.E.; Slagowski, J.L. (1978) Metolachlor (Dualฎ 8E); Atrazine
(AAtrexฎ SOW); Paraquat (Paraquat CL): AG-A No. 4964. (Unpublished
study received Mar 16, 1979 under 100-583; prepared in cooperation with
EN-CAS Laboratories and Chevron Chemical Co., submitted by Ciba-Geigy
Corp., Greensboro, N.C.; CDL:237819-G)
00016441 Thomas, J.; Herman, D.; Slagowski, J.L. (1977) Residue Report: Field Corn:
AG-A No. 4167II. (Unpublished study received Nov 10,1977 under
100-EX-59; prepared in cooperation with Chevron Chemical Co., submitted
by Ciba-Geigy Corp., Greensboro, N.C.; CDL:232192-1)
160
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BIBLIOGRAPHY
MRID
CITATION
00016442 Coan, R.M.; Karusta, G.; Slagowski, J.L. (1977) Residue Report: Field
Cora: AG-A No. 4187 II,III. (Unpublished study received Nov 10, 1977
under 100-EX-59; prepared in cooperation with Chevron Chemical Co.,
submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:232192-J)
00016444 Westmoreland, W.G.; Slagowski, J.L. (1977) Residue Report: Field Corn:
AG-A No. 4247 II,III. (Unpublished study received Nov 10, 1977 under
100-EX-59; prepared in cooperation with Chevron Chemical Co., submitted
by Ciba-Geigy Corp., Greensboro, N.C.; CDL: 232192-L)
00016445 Davidson, W.E.; Slagowski, J.L. (1977) Residue Report: Field Corn: AG-A
No. 4288 1,11. (Unpublished study received Nov 10, 1977 under
100-EX-59; prepared in cooperation with Chevron Chemical Co., submitted
by Ciba-Geigy Corp., Greensboro, N.C.; CDL: 232192-M)
00022923 Hill, E.; Heath, R.; Spann, J. (1975) U.S. Department of Interior, Fish and
Wildlife: Lethal Dietary Toxicity of Environmental Pollutants to Birds.
Patuextant Wildlife Research Center.
00023131 Leary, J.B.; Slagowski, J.L.; Marxmiller, R.L. et al. (1979) Summary of
Residue Data. (Unpublished study received Jan 10, 1980 under 201-279;
prepared in cooperation with Chevron Chemical Co. and others, submitted
by Shell Chemical Co., Washington, D.C.;CDL:241596-B)
00023329 Ross, J.A.; Tucker, B.V.; White, J.C.; et al. (1978) Residues in Sour
Cherries, Plums, Grapes, Pecans, Filberts, Lemons and Oranges Resulting
from the Application of Simazine in Tank Mixture with Paraquat: Report
No. ABR-78042. (Unpublished study received Aug 2, 1978 under 100-437;
prepared in cooperation with Chevron Chemical Co. and En-Cas
Laboratories, submitted by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:234570-A)
00023512 Houseworth, L.D.; Schnappinger, H.G.; Slagowski, J.L.; et al. (1979) Tank
Mixes of Metolachlor (6E, 8E) plus Simazine and/or Atrazine plus Paraquat
or GlyphosateCorn: Summary of Residue Data: Report No. ABR-79105.
(Unpublished study received Dec 10,1979 under 100-583; prepared in
cooperation with Chevron Chemical Co. and others, submitted by
Ciba-Geigy Corp., Greensboro,N.C.; CDL:241647-A)
00023883 Thompson, R.; Jensen, ?; Elmore, C.; et al. (1974) Crop Residue Studies
Summary for Devrinol 50-WP (4 Lbs. A.I./A) Tank Mixed with Simazine
80-WP (0.5-1 Lb.A.I./A) and/or Paraquat (1 Lb.A.I./A) in
California/Arizona. (Unpublished study received Dec 17, 1974 under
161
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BIBLIOGRAPHY
MRID
CITATION
476-2150; prepared in cooperation with Kern County Land Company and
others, submitted by Stauffer Chemical Co., Richmond, Calif.;
CDL:028423-J)
00025268 Freeman, C.R.; Dewey, M.L.; Kensler, D.L., Jr.; et al. (1975) Summary:
Residues in Soybeans after a Tank-Mix, No-Till Application of Paraquat
CL, Lasso, and Sencor. (Unpublished study received Jul 2, 1975 under
239-2186; prepared in cooperation with Morse Laboratories, Inc., submitted
by Chevron Chemical Co., Richmond, Calif.; CDL:119803-C)
00025269 Chevron Chemical Company (1974) Analysis of Paraquat Residues. Method
RM-8-6 dated Nov 5, 1974. (Unpublished study received Jul 2, 1975 under
239-2186; CDL:119803-D)
00026963 Freeman, C.R.; Dewey, M.L.; Pinkerton, G.; et al. (1975) Summary:
Residues of Paraquat and Atrazine in Grain Sorghum after a Tank-Mix,
No-Till Application. (Unpublished study received Jun 24, 1975 under
239-2186; prepared in cooperation with Morse Laboratories, Inc., submitted
by Chevron Chemical Co., Richmond,Calif.; CDL:110503-B)
00027178 Kalens, K.J.; Kirby, B.W.; Kincade, R.T.; et al. (1971) Summary Residue
Tests in Grain Sorghum Resulting from Postemergence Directed Sprays of
Paraquat Alone or a Tank-Mixture of Paraquat and Atrazine. (Unpublished
study received Jun 24,1975 under 239-2186; prepared in cooperation with
Pattison's Laboratories, Inc. and others, submitted Chevron Chemical Co.,
Richmond, Calif.; CDL:221809-B)
00027298 Thompson, J.P.; Rivers, J.B.; Reddy, K.P.; et al. (1968) Residue Data
Sheet: Test No. T-1466. (Unpublished study including test nos. T-1467,
T-1462, T-1463..., received Feb 8, 1968 under 7F0592; prepared in
cooperation with U.S. Laboratories, Inc. andPattison's Laboratories, Inc.,
submitted by Chevron Chemical Co., Richmond, Calif.; CDL:090763-A)
00027311 Imperial Chemical Industries, Limited (1965) [Residues of Gramoxone in
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Toxicology and Applied Pharmacology (22):556-561. (Alos in unpublished
submission received Oct. 26, 1977 under 1016-69; submitted by Union
Carbide Corp., Arlington VA; CDL:096397-E)
00103245 Slagowski, J. (1981) Residue Data Sheet: [Paraquat]. (Unpublished study
received Jun 4, 1982 under 239-2186; submitted by Chevron Chemical Co.,
Richmond, CA; CDL-.247643-A)
00105060 Chevron Chemical Co. (1980) Residue Chemistry Data to Support an
Amendment of the Paraquat CL Label for Potatoes to Include
Preplant-preemergence Treatment by Ground or Aerial Application.
(Unpublished study received Jun 16, 1982 under 239-2186; CDL:
247683-A)
00105061 Chevron Chemical Co. (1981) Residue Chemistry Data to Support an
Amendment of the Paraquat CL Label for Alfalfa to Add Aerial Application.
(Unpublished study received Jun 16, 1982 under 239-2186; CDL:247684-A)
00106570 Illinois (1982) Ortho Paraquat CL Special Local Need 24(C) Request:
No-till Sunflowers. (Compilation; unpublished study received Jul 12, 1982
under IL 82/11; CDL:247838-A)
00109728 Chevron Chemical Co. (1974) Summary: Residues in Soybeans after a
Tank-mix, No-till Application of Paraquat CL, Lasso, and Lorox.
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Technical (SX-1305): Project No. 162-138; S-1994. Final rept.
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00110454 Fink, R.; Beavers, J.; Joiner, G.; et al. (1982) One-generation
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Description of the Analytical Method Used. (Compilation; unpublished
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[Paraquat]. (Compilation; unpublished study received Feb 24, 1975 under
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(Compilation; unpublished study received Jun 9, 1975 under 5F1639;
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Chevron Chemical Co. (1977) Residue Chemistry Data To Support
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Chevron Chemical Co. (1977) Residue Chemistry Data To Support
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00114473 Wheeler, R. (1978) 48 Hour Acute Static Toxicity of Paraquat Dichloride
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00126671 Chevron Chemical Co. (1983) Residue Chemistry Data to Support a
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00137859 Interregional Research Project No. 4 (1977) The Results of Tests on the
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00138258 Interregional Research Project No. 4 (1976) The Results of Tests on the
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41151502 Roper, E. (1988) Paraquat: Magnitude of Residues in Fresh and Dried Figs:
Laboratory Project ID 148-88-MR-24: 148-88-MR-25. Unpublished study
prepared by ICI Americas, Inc. 47 p.
185
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41151503 Roper, E. (1989) Paraquat: Magnitude of Residues in Cucumbers, Melons
and Summer Squash: Laboratory Project ID 148-88-MR-08:
148-88-MR-09. Unpublished study prepared by ICI Americas, Inc. 77 p.
41151504 Roper, E. (1988) Paraquat: Magnitude of Residues in Green Bean Hay:
Laboratory Project ID 148-88-MR-31: Report No. TMR0018B.
Unpublished study prepared by ICI Americas, Inc. 33 p.
41151505 Roper, E. (1988) Paraquat: Magnitude of Residues in Green Pea Hay:
Laboratory Project ID 148-88-MR-07: Report No. TMR0019B.
Unpublished study prepared by ICI Americas, Inc. 37 p.
41151506 Roper, E. (1988) Paraquat: Magnitude of Residues in Sweet Corn Forage
and Ears: Laboratory Project ID 148-88-MR-13: Report No. TMR0020B.
Unpublished study prepared by ICI Americas, Inc. 50 p.
41151507 Roper, E. (1988) Paraquat: Magnitude of Residues in Fresh Market
Tomatoes (Exaggerated Rate): Laboratory Project ID 4-148-87-03: Report
No. TMR0021B. Unpublished study prepared by ICI Americas, Inc. 27 p.
41151508 Roper, E. (1989) Paraquat: Magnitude of Residues in Potatoes and
Processing Fractions: Laboratory Project ID 148-88-PR-01: Report No.
TMU0022B. Unpublished study prepared by ICI Americas, Inc. 68 p.
41151509 Roper, E. (1989) Gramoxone Super: Residues of Paraquat in Clover Forage
and Hay: Laboratory Project ID 148-88-MR-20: Report No. TMR0023B.
Unpublished study prepared by ICI Americas, Inc. 38 p.
41151510 Roper, E. (1988) Paraquat: Magnitude of Residues in Whole Tomatoes and
Processing Fractions: Laboratory Project ID 148-88-PR-03: Report No,
TMR0024B. Unpublished study prepared by ICI Americas, Inc. 44 p.
41151511 Roper, E. (1989) Stability of Weathered Residues of Paraquat on Birdsfoot
Trefoil Forage and Hay in Frozen Storage: Laboratory Project ID
PRO/R/014/88: Report No. TMR0025B. Unpublished study prepared by
ICI Americas, Inc. 22 p.
41151512 Roper, E. (1989) Paraquat: Magnitude of Residues in Sunflower Forage and
Seeds: Laboratory Project IDs: 148-88-MR-28: 148-88-MR-30.
Unpublished study prepared by ICI Americas, Inc. 49-p.
186
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41151513 Roper, E. (1989) Paraquat: Magnitude of Residues in Turnip Tops:
Laboratory Project ID 148-88-MR-04: Report No. TMR0030B.
Unpublished study prepared by ICI Americas, Inc. 38 p.
41151514 Roper, E. (1989) Paraquat: Magnitude of Residues in Sugarbeet Tops and
Roots: Laboratory Project ID 148-88-MR-02: Report No. TMR0031B.
Unpublished study prepared by ICI Americas, Inc. 45 p.
41151515 Roper, E. (1989) Paraquat: Magnitude of Residues in Grass Forage and Hay
(Eastern Pastures): Laboratory Project ID 148-88-MR-18: Report No.
TMR0032B. Unpublished study prepared by ICI Americas, Inc. 50 p.
41151516 Roper, E. (1989) Paraquat: Magnitude of Residues in Grass Forage and Hay
(Western Use Rangeland): Laboratory Project ID 148-88-MR-17: Report
No. TMR0033B. Unpublished study prepared by ICI Americas, Inc. 37 p.
41151517 Roper, E. (1989) Paraquat: Magnitude of Residues in Wheat Processing
Fractions: Laboratory Project ID 148-88-PR-06: Report No. TMR0034B.
Unpublished study prepared by ICI Americas, Inc. 40 p.
41151518 Roper, E. (1988) Paraquat: Magnitude of Residues in Sugarcane and
Processing Fractions: Laboratory Project ID 148-88-PR-l 1: Report No.
TMR0035B. Unpublished study prepared by ICI Americas, Inc. 32 p.
41151519 Roper, E. (1989) Paraquat: Magnitude of Residues in Sugar Beet Processing
Fractions: Laboratory Project ID 148-88-PR-02: Report No. TMR0036B.
Unpublished study prepared by ICI Americas, Inc. 49 p.
41151520 Roper, E. (1989) Paraquat: Magnitude of Residues in Sorghum and
Processing Fractions: Laboratory Project ID 148-88-PR-05. Unpublished
study prepared by ICI Americas, Inc. 41 p.
41151521 Roper, E. (1988) Paraquat: Magnitude of Residues in Hops and Processing
Fractions: Laboratory Project ID 148-88-PR-09: Report No. TMR0038B.
Unpublished study prepared by ICI Americas, Inc. 58 p.
41151522 Roper, E. (1988) Paraquat: Magnitude of Residues in Olives and Processing
Fractions: Project ID 148-88-PR-27. Unpublished study prepared by ICI
Americas, Inc. 41 p.
187
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41151523 Roper, E. (1988) Paraquat: Magnitude of Residues in Field Corn Forage,
Silage, Kernels and Fodder: Project ID 4-148-87-14. Unpublished study
prepared by ICI Americas, Inc. 144 p.
41151524 Roper, E. (1988) Paraquat: Magnitude of Residues in Soybean Forage, Hay
and Seed, Harvest Aid Use: Project ID 148-88-MR-34 and 148-88-MR-35.
Unpublished study prepared by ICI Americas, Inc. 133 p.
41151525 Roper, E. (1988) Paraquat: Magnitude of Residues in Wheat Forage, Straw
and Gram: Project ID 4-148-87-06. Unpublished study prepared by ICI
Americas, Inc. 95 p.
41151526 Roper, E. (1989) Paraquat: Magnitude of Residues in Pasture Grass
(Western Use Pastures): Project ID 148-88-MR-16. Unpublished study
prepared by ICI Americas, Inc. 3 6 p.
41151527 Roper, E. (1989) Paraquat: Magnitude of Residues in Soybean Forage and
Hay: Project ID 148-88-MR-33: Report No. TMR0045B. Unpublished
study prepared by ICI Americas, Inc. 46 p.
41151528 Roper, E. (1989) Paraquat: Magnitude of Residues in Field Corn Grain and
Processing Fractions: Project ID 148-88-PR-04: Report No. TMR0046B.
Unpublished study prepared by ICI Americas, Inc. 48 p.
41151529 Roper, E. (1989) Paraquat: Magnitude of Residues in Coffee Beans and
Processing Fractions: Project ID 148-88-MR-22: Report No. TMR0047B.
Unpublished study prepared by ICI Americas, Inc. 45 p.
41151530 Roper, E. (1988) Paraquat: Magnitude of Residues in Soybean Forage, Hay
and Seed: Project ID 4-148-87-18: Report No. TMR0049B. Unpublished
study prepared by ICI Americas, Inc. 85 p.
41151531 Roper, E. (1988) Paraquat: Magnitude of Residues in Sorghum: Project ID
4-148-87-20: Report No. TMR0050B. Unpublished study prepared by ICI
Americas, Inc. 120 p.
41151532 Roper, E. (1988) Gramoxone Super: Residues of Paraquat in Fresh Market
and Dried Prunes: Project ID 4-148-87-05: Report No. WRC 89-120.
Unpublished study prepared by ICI Americas, Inc. 29 p.
188
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41151533 Roper, E. (1988) Paraquat: Residues of Paraquat in Pineapple and
Processing Fractions, 1988: Project ID 148-88-PR-10: Report No.
TMU3658/B. Unpublished study prepared by ICI Americas, Inc. 37 p.
41151534 Roper, E. (1988) Paraquat Residues on Pineapple Forage, 1988: Project ID
148-88-MR-14: Report No. TMU3659/B. Unpublished study prepared by
ICI Americas, Inc. 22 p.
41151535 Roper, E. (1989) Stability of Paraquat Residues in Frozen Prune Samples:
12 Months Storage: Project ID PRO/R/010/88.: Report No. WRC 89-123.
Unpublished study prepared by ICI Americas, Inc. 29 p.
41151536 Roper, E. (1989) Stability of Paraquat Residues in Frozen Potato Samples:
12 Months Storage: Project ID PRO\R\009\88: Report No. TMU3662/B.
Unpublished study prepared by ICI Americas, Inc. 28
41151537 Roper, E. (1989) Stability of Paraquat Residues in Frozen Tomato Samples:
12 Months Storage: Project ID PRO\R\009\88: Report No. WRC 89-125.
Unpublished study prepared by ICI Americas, Inc. 29 p.
41151538 Roper, E. (1989) Stability of Paraquat Residues in Frozen Corn Grain
Samples: 12 Months Storage: Project ID PRO\R\010\88: Report No.
TMU3664/B. Unpublished study prepared by ICI Americas, Inc. 27 p.
41151539 Roper, E. (1989) Stability of Paraquat Residues in Frozen Corn Fodder
Samples: 12 Months Storage: Project ID PRO\R\010\88: Report No.
TMU3665/B. Unpublished study prepared by ICI Americas, Inc. 27 p.
41151540 Roper, E. (1989) Stability of Paraquat Residues in Frozen Corn Forage
Samples: 12 Months Storage: Project ID PRO\R\009\88: Report No.
TMC3666/B. Unpublished study prepared by ICI Americas, Inc. 27 p.
41151541 Roper, E. (1989) Stability of Paraquat Residues in Frozen Corn Silage
Samples: 12 Months Storage: Project ID PRO\R\009\88: Report No.
TMU3667/B. Unpublished study prepared by ICI Americas, Inc.
41151542 Roper, E. (1988) Gramoxone Super: Residues of Paraquat in Birdsfoot
Trefoil Forage and Hay, 1988: Project ID 148-88-MR-21: Report No.
TMU3672/B. Unpublished study prepared by ICI Americas, Inc. 30 p.
189
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during 1987-89; analytical report. Unpublished study performed and
submitted by ICI Americas, Inc., Wilmington, DE.
41317401 ICI Americal, Inc. (1989) Paraquat: Oncogenic Rectification,
Toxicology Overview. Unpublished study.
41319301 Vickers, J.A., A.D. Hurt, and D.W. Bewick. 1989. Paraquat: degradation in
aerobic soil. Laboratory Project No. 88JH386/ReportNo. RJ0788B.
Unpublished study performed and submitted by ICI Americas Inc.,
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41319302 Vickers, J.A., A.D. Hurt, and D.W. Bewick. 1989. Paraquat: degradation in
anaerobic soil. Laboratory Project No. 88JH386/Report No. RJ0810B.
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41352101 Anderson, L.; Embury, G.; Hoag, R.; et al. (1989) Paraquat: Short Term
Field Soil Dissipation Under IN-use Conditions in the USA (Pullman,
Washington) during 1987-1989: Lab Project Number: PP148BD04: Report
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41352102 Anderson, L.; Embury, G.; Hoag, R. Etal. (1989) Paraquat: Short Term
Field Soil Dissipation under In-use Conditions in the USA (Clermont,
Florida) During 1987-1989: Lab Project Number: PP148BD04: Report
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41645601 Vickers, J.; Hurt, A.; Bewick, D. (1990) Paraquat: Rotational Crop Study:
Lab Project Number: 88JH074. Unpublished study prepared by ICI
Agrochemicals, Jealott's Hill Research Station. 37 p.
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Residue Chemistry Reregistration Standard Update. Unpublished study
prepared by ICI Americas Inc. 56 p.
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42217403 Kennedy, S. (1986) The Determination of Residues of Paraquat in Soil: A
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Water and Other Liquid Samples: A Spectrophotometric Method: Lab
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and Meal: Addendum to MRID 41151501: Lab Project Number: 148-88-
MR-19: TMR0014B: WRC 89-080. Unpublished study prepared by ICI
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42217407 Roper, E. (1988) Paraquat: Magnitude of Residues in Fresh and Dried Figs:
Addendum to MRID 41151502: Lab Project Number: 148-88-MR-24: 148-
88-MR-25: TMR0015B: WRC 89-81. Unpublished study prepared by ICI
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and Summer Squash: Addendum to MRID 41151503: Lab Project Number:
148-88-MR-08/09/10: TMR0017B: WRC 89-083. Unpublished study
prepared by ICI Americas, Inc. 4 p.
42217409 Roper, E. (1988) Paraquat: Magnitude of Residues in Green Bean Hay:
Addendum to MRID 41151504: Lab Project Number: 148-88-MR-31: WRC
89-084. Unpublished study prepared by ICI Americas, Inc. 4 p.
42217410 Roper, E. (1988) Paraquat: Magnitude of Residues in Green Pea Hay:
Addendum to MRID 41151505: Lab Project Number: 148-88-MR-07:
TMR0019B: WRC 89-085. Unpublished study prepared by ICI Americas,
Inc. 4 p.
42217411 Roper, E. (1988) Paraquat: Magnitude of Residues in Sweet Corn Forage
and Ears: Addendum to MRID 41151506: Lab Project Number:
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42217412 Roper, E. (198'8) Paraquat: Magnitude of Residues in Fresh Market
Tomatoes (Exaggerated Rate): Addendum to MRID 41151507: Lab Project
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prepared by ICI Americas, Inc. 4 p.
42217413 Roper, E. (1989) Paraquat: Magnitude of Residues in Potatoes and
Processing Fractions: Addendum to MRID 41151508: Lab Project Number:
148-88-PR-01: TMU0022B: WRC 89-088. Unpublished study prepared by
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42217414 Roper, E. (1989) Gramoxone Super: Residues of Paraquat in Clover Forage
and Hay: Addendum to MRID 41151509: Lab Project Number: 148-88-MR-
20: TMR0023B: WRC 89-089. Unpublished study prepared by ICI
Americas Inc. 4 p.
42217415 Roper, E. (1988) Paraquat: Magnitude of Residues in Whole Tomatoes and
Processing Fractions: Addendum to MRID 41151510: Lab Project Number:
148-88-PR-03: TMR0024B: WRC 89-90. Unpublished study prepared by
ICI Americas Inc. 4 p.
42217416 Roper, E. (1989) Paraquat: Magnitude of Residues in Sunflower Forage and
Seeds: Addendum to MRID 41151512: Lab Project Number: 148-88-MR-
28: 148-88-MR-30: TMR0029B: WRC 89-95. Unpublished study prepared
by ICI Americas Inc. 4 p.
42217417 Roper, E. (1989) Paraquat: Magnitude of Residues in Turnip Tops: Lab
Project Number: 148-88-MR-04: TMR0030B: WRC 89-96. Unpublished
study prepared by ICI Americas Inc. 4 p.
42217418 Roper, E. (1989) Paraquat: Magnitude of Residues in Sugarbeet Tops and
Roots: Lab Project Number: 148-88-MR-02: TMR0031B: WRC 89-97.
Unpublished study prepared by ICI Americas Inc. 4 p.
42217419 Roper, E. (1988) Paraquat: Magnitude of Residues in Grass Forage and Hay
(Eastern Pastures): Lab Project Number: 148-88-MR-18: TMR0032B: WRC
89-98. Unpublished study prepared by ICI Americas Inc. 5 p.
192
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42217420 Roper, E. (1989) Paraquat: Magnitude of Residues in Grass Forage and Hay
(Western Pastures): Lab Project Number: 148-88-MR-17: TMR003B: WRC
89-99. Unpublished study prepared by ICI Americas Inc. 5 p.
42217421 Roper, E. (1989) Paraquat: Magnitude of Residues in Wheat Processing
Fractions: Lab Project Number: 148-88-PR-06: TMR0034B: WRC 89-100.
Unpublished study prepared by ICI Americas Inc. 4 p.
42217422 Roper, E. (1988) Paraquat: Magnitude of Residues in Sugarcane and
Processing Fractions: Lab Project Number: 148-88-PR-l 1: TMR0035B:
WRC 89-101. Unpublished study prepared by ICI Americas Inc. 4 p.
42217423 Roper, E. (1989) Paraquat: Magnitude of Residues in Sugarbeet Processing
Fractions: Lab Project Number: 148-88-PR-02: TMR0036B: 89-102.
Unpublished study prepared by ICI Americas Inc. 4 p.
42217424 Roper, E. (1989) Paraquat: Magnitude of Residues in Sorghum and
Processing Fractions: Lab Project Number: 148-88-PR-05: TMR0037B:
WRC89-103. Unpublished study prepared by ICI
42217425 Roper, E. (1989) Paraquat: Magnitude of Residues in Pasture Grass
(Western Use Pastures): Lab Project Number: 148-88-MR-16: TMR0044B:
WRC 89-110. Unpublished study prepared by ICI Americas Inc. 5 p.
42217426 Roper, E. (1989) Paraquat: Magnitude of Residues in Soybean Forage and
Hay: Lab Project Number: 148-88-MR-3: TMR0045B: WRC 89-111.
Unpublished study prepared by ICI Americas Inc. 4 p.
42217427 Roper, E. (1989) Paraquat: Magnitude of Residues in Field Corn Grain and
Processing Fractions: Lab Project Number: 148-88-PR-04: TMR0046B:
WRC 89-112. Unpublished study prepared by ICI Americas Inc. 4 p.
42217428 Roper, E. (1989) Paraquat: Magnitude of Residues in Coffee Beans and
Processing Fractions: Lab Project Number: 148-88-MR-22: TMR0047B:
WRC 89-113. Unpublished study prepared by ICI Americas Inc. 4 p.
42217429 Roper, E. (1989) Paraquat: Magnitude of Residues in Soybean Forage, Hay
and Seed: Lab Project Number: 4-148-87-18: TMR0049B: WRC 89-115.
Unpublished study prepared by ICI Americas Inc. 4 p.
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42217430 Roper, E. (1989) Paraquat: Magnitude of Residues in Sorghum: Lab Project
Number: 4-148-87-20: 4-148-87-21: TMR0050B. Unpublished study
prepared by ICI Americas Inc. 5 p.
42217431 Roper, E. (1989) Gramoxone Super: Residues of Paraquat in Fresh Market
and Dried Prunes: Lab Project Number: 4-148-87-05: TMU3657/B: WRC
89-120. Unpublished study prepared by ICI Americas Inc. 4 p.
42217432 Roper, E. (1988) Paraquat: Residues of Paraquat in Pineapple and
Processing Fractions: Lab Project Number: 1488-88-PR-10: TMU3658/B:
WRC 89-121. Unpublished study prepared by ICI
42217433 Roper, E. (1988) Paraquat Residues on Pineapple Forage, 1988: Lab Project
Number: 148-88-MR-14: TMU3659/B: WRC 89-122. Unpublished study
prepared by ICI Americas Inc. 4 p.
42217434 Roper, E. (1988) Gramoxone Super: Residues of Paraquat in Birdsfoot
Trefoil Forage and Hay, 1988: Lab Project Number: 148-88-MR-21:
TMU3672/B: WRC 89-130. Unpublished study prepared by ICI Americas
Inc. 4 p.
42217435 Roper, E. (1988) Paraquat: Magnitude of Residues in Hops and Processing
Fractions: Lab Project Number: 148-88-PR-09: TMR0038B: WRC 89-104.
Unpublished study prepared by ICI
42217436 Roper, E. (1988) Paraquat: Residues of Paraquat from Fortified Samples of
Olives and Processed Fractions: Lab Project Number: 148-88-PR-27:
TMR0039B: WRC 89-105. Unpublished study prepared by ICI Americas
Inc. 4 p.
42217437 Roper, E. (1988) Paraquat: Magnitude of Residues in Field Corn, Forage,
Silage Kernels and Fodder: Lab Project Number: 4-148-87-14:148-88-MR-
11: TMR0040B. Unpublished study prepared by ICI Americas Inc. 5 p.
42217438 Roper, E. (1989) Paraquat: Magnitude of Residues in Soybean Forage, Hay
and Seed Harvest Aid Use: Lab Project Number: 148-88-MR-34: 148-88-
MR-35: TMR0041B. Unpublished study prepared by ICI Americas Inc. 5 p.
194
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42217439 Roper, E. (1988) Paraquat: Magnitude of Residues in Wheat Forage, Straw
and Grain: Lab Project Number: 4-148-87-06: 4-148-8722: 4-148-87-23.
Unpublished study prepared by ICI Americas Inc. 5 p.
42217440 Roper, E. (1991) Stability of Paraquat Residues in Frozen Prune Samples:
25 Months Storage: Lab Project Number: PRO\R\010\88; TMR 0228B;
WRC-90-464. Unpublished study prepared by ICI Americas Inc. 38 p.
42217441 Roper, E. (1991) Stability of Paraquat Residues in Frozen Tomato Samples:
26 Months Storage: Lab Project Number: PRO\R\009\88: TMR0226B:
WRC-90-462. Unpublished study prepared by ICI Americas Inc. 36 p.
42217442 Roper, E. (1991) Stability of Paraquat Residues in Frozen Potato Samples:
26 Months Storage: Lab Project Number: PRO\R\009\88: TMR0227B:
WRC 90-463. Unpublished study prepared by ICI Americas Inc. 36 p.
42217443 Roper, E. (1991) Stability of Weathered Residues of Paraquat on Birdsfoot
Trefoil Forage and Hay in Frozen Storage: Lab Project Number:
PRO\R\014\88: TMR0267B: WRC-90-549. Unpublished study prepared by
ICI Americas Inc. 27 p.
42217444 Roper, E. (1991) Stability of Paraquat Residues in Frozen Corn Forage
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TMR0234B: WRC 90-476. Unpublished study prepared by ICI Americas
Inc. 35 p.
42217445 Roper, E. (1991) Stability of Paraquat Residues in Frozen Corn Fodder
Samples: 26 Months Storage: Lab Project Number: PRO\R\009\88:
TMR0232B: WRC-90-474. Unpublished study prepared by ICI Americas
Inc. 35 p.
42217446 Roper, E. (1991) Stability of Paraquat Residues in Frozen Corn Silage
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TMR0233B: WRC-90-475. Unpublished study prepared by ICI Americas
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42217447 Roper, E. (1991) Stability of Paraquat Residues in Frozen Corn Grain
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42217448 Anderson, L.; Boseley, A.; Earl, M. (1991) Paraquat: Storage Stability of
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RJO908B. Unpublished study prepared by ICI Americas Inc. 17 p.
42217449 Anderson, L.; Boseley, A.; Earl, M. (1991) Paraquat: Storage Stability of
Residues in Frozen Eggs: Lab Project Number: 88JH109: RJO912B.
Unpublished study prepared by ICI Americas Inc. 17 p.
42217450 Earl, M.; Boseley, A.; Muir, G. et al. (1991) Paraquat: Storage Stability of
the Residue in Frozen Carrot, Cabbage and Wheat Grain at <-18 Degrees
Centigrade (Interim): Lab Project Number: PP148BCO1: RJO729B.
Unpublished study prepared by ICI Americas Inc. 26 p.
42297601 Robson, C; Nelson, N.; J.; et al. (1992) Product Chemistry Registration
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P551-207. Unpublished study prepared by ICI Americas, Inc. 77 p.
42324301 Leahy, J. (1992) Overview and Summary of Paraquat Dichloride: Nature of
Residue in Plants. Unpublished study prepared by ICI Americas, Inc. 46 p.
42324302 Leahy, J. (1992) Overview and Summary of Paraquat Dichloride: Nature of
Residue in Livestock.Unpublished study prepared by ICI Americas, Inc. 8p.
42588201 Robson, C.; Nelson, N.; Rhodes, M. (1992) Supplement to MRID
40479001, 42297601, and 40624701: Product Chemistry Registration Data
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26 p.
42601001 Canning, L.; White, J. (1992) Paraquat: A Glasshouse Study to Evaluate
the Effects on Vegetative Vigor of a 300 g ai litre-1 (2.5 Ib ai US gal-1)
Soluble Concentrate Formulation on Terrestrial Non-Target Plants: Lab
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Agrochemicals. 73 p.
42601002 Smyth, D.; Sankey, S.; Penwell, A. (1992) Paraquat Dichloride: Toxicity to
the Green Alga Selenastrum capricornutum: Lab Project Number:
BL4578/B: T168/G (FT11/92). Unpublished study prepared by Imperial
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42601003 Smyth, D.; Sankey, S.; Cornish, S.; et al (1992) Paraquat Dichloride:
Toxicity to the Duckweed Lemna Gibba: Lab Project Number: BL4493/B:
T168/E (FT10/92). Unpublished study prepared by Imperial Chemical
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42601004 Smyth, D.; Sankey, S.; Penwell, A. (1992) Paraquat Dichloride: Toxicity to
the Marine Alga Skeletonema costatum: Lab Project Number: BL4580/B:
T168/C (FT08/92). Unpublished study prepared by Imperial Chemical
Industries PLC. 22 p.
42601005 Smyth, D.; Sankey, S.; Cornish, S. (1992) Paraquat Dichloride: Toxicity to
the Blue-green Alga Anabaena flos-aquae: Lab Project Number: BL4579/B:
T168/B (FT07/92). Unpublished study prepared by Imperial Chemical
Industries PLC. 26 p.
42601006 Smyth, D.; Sankey, S.; Cornish, S. (1992) Paraquat Dichloride: Toxicity to
the Freshwater diatom Navicula pelliculosa: Lab Project Number:
BL4464/B: T168/D (FT09/92). Unpublished study prepared by Imperial
Chemical Industries PLC. 22 p.
42639601 Canning, L.; White, J. (1992) Paraquat: A Glasshouse Study to Evaluate
the Effects on Seedling Emergence of a 300 g ai litre-1 (2.5 Ib ai US gal-1)
Soluble Concentrate Formulation on Terrestrial Non-Target Plants: Lab
Project Number: 92JH089: RJ1280B. Unpublished study prepared by ICI
Agrochemicals. 56 p.
42670801 White, J.; Rhodes, M. (1993) Paraquat: Response to Residue Chemistry
Review of Tolerance Petition No. 5F3188. Unpublished study prepared by
Zeneca Inc. 236 p.
42684101 Rhodes, M. (1993) Paraquat: Response to Residue Chemistry Review of
Pesticide Petition No. 5F1625 and Food Additive Petition No. 5H5088.
Unpublished study prepared by Zeneca Inc. lip.
42738701 Anderson, L, R.E. Hoag, C.W. Anders, and M. Earl. 1992. Paraquat: field
soil dissipation under in-use conditions in the USA during 1987-91 (Visalia,
California). Laboratory Report No. PP148BD05/Report No. RJ1191B.
Unpublished study performed by ICI Agrochemicals, Berkshire, UK, and
submitted by ICI Americas, Inc., Wilmington, DE.
197
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BIBLIOGRAPHY
MRTO
CITATION
42738702 Anderson, L, R.E. Hoag, C.W. Anders, and M. Earl. 1992. Paraquat: field
soil dissipation under in-use conditions in the USA during 1987-89 (Leland,
Mississippi). Laboratory Report No. PP148BD05/Report No. RJ1206B.
Unpublished study performed by ICI Agrochemicals, Berkshire, UK, and
submitted by ICI Americas, Inc., Wilmington, DE.
42738703 Earl, M., G.T. Emburey, J.C. Scholey and L. Anderson. 1992. Paraquat:
Storage stability of the residue in frozen soil. Laboratory Report No.
RJ1152B/ProjectNo. PP148BC01. Unpublished study performed by ICI
Agrochemicals, Berkshire, UK, and submitted by ICI Americas, Inc.,
Wilmington, DE.
42802101 Anderson, L, R.E. Hoag, J. Safford, C.W. Anders, and M. Earl. 1992.
Paraquat: field soil dissipation under in-use conditions in the USA during
1987-91 (Champaign, Illinois). Laboratory Report Np. PP148BD05/Report
No. RJ1187B. Unpublished study performed by ICI Agrochemicals,
Berkshire, UK, and submitted by ICI Americas, Inc., Wilmington, DE.
42802102 Anderson, L, R.E. Hoag, C.W. Anders, and M. Earl. 1992. Paraquat: field
soil dissipation under in-use conditions in the USA during 1987-89
(Goldsboro, North Carolina). Laboratory Report No. PP148BD05/Report
No. RJ1146B. Unpublished study performed by ICI Agrochemicals,
Berkshire, UK, and submitted by ICI Americas, Inc., Wilmington, DE.
42961401 Rhodes, M. (1993) Response to Paraquat Dichloride Residue Chemistry
Review of ZENECA's Response to the Task 4: Reregistration Standard
Update (CBRS Nos. 9032 and 9509): Lab Project Number. Unpublished
study prepared by Zeneca Inc. 45 p.
43099701 Robson, C.; Nelson, N.; Rhodes, M. (1993) Product Chemistry Registration
Data Summary and Overview: Zeneca's Response to Agency Review
Comments Provided March 19 and November 16, 199^3: Supplement to
MRED 40479001, 42297601, 40624701, and 42588201. Unpublished Study.
31 p.
43226901 Rhodes, M. (1994) Addendum to MRID 42961401: Response to Paraquat
Dichloride Residue Chemistry Review of Zeneca's Response to the Task 4:
Reregistration Standard Update (CBRS Nos. 9032 and 9509). Unpublished
study prepared by Zeneca Inc. 6 p.
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BIBLIOGRAPHY
MRID
CITATION
43226902
43226903
43226904
43429001
43492601
43492602
43492603
43618201
Anderson, L. (1994) PARAQUAT: Validation of a Residue Analytical
Method for the Determination of Paraquat in Animal Products: Lab Project
Number: 94JH221: RJ1600B. Unpublished study prepared by Jealotts Hill
Research Station, Zeneca Agrochemicals. 56 p.
Coombe, N. (1994) Paraquat: Animal Tissue Method Validation-ZENECA
Agrochemicals SOP RAM/004/03: Lab Project Number: CEMS-299:
CTR-299: CEMR-299. Unpublished study prepared by Jealotts Hill
Research Station, Zeneca Agrochemicals. 88 p.
Roper, E. (1993) GRAMQXONE EXTRA: Residues of Paraquat in Soybean
Grain Dust Following Harvest Aid Application: Lab Project Number:
PARA-92-PR-01: RR 93-081B. Unpublished study prepared by Zeneca Ag
Products. 45 p.
Nelson, N.; Li, R.; Robson, C.; et al. (1994) Supplement to MRID
40479001, 42297601, 40624701, 42588201, and 43099701: Product
Chemistry Registration Data Summary and Overview: (Paraquat
Dichloride): Project Nos. WRC-94-060; TMR0565A; PAM 658/3.
Unpublished study prepared by Zeneca, Inc. 42 p
Rhodes, M. (1994) 30-Day Response to Paraquat Dichloride Residue
Chemistry Reviews Dated May 23, 1994 and August 1, 1994 Lab Project
Number: RAM 004/05. Unpublished study prepared by Zeneca, Inc. 77 p.
Grout, S. (1994) Paraquat: Quantification and Characterization of
Radioactive Residues in Root and Leafy Crop after Preplant Soil Treatment:
Lab Project Number: 93JH105. Unpublished study prepared by Zeneca
Agrochemicals (Zeneca Ltd). 39 p.
Grout, S. (1994) Paraquat: Quantification and Characterization of
Radioactive Residues in Root and Oilseed Crop after Desiccant Treatment of
Foliage: Lab Project Number: 92JH243. Unpublished study prepared by
Zeneca Agrochemicals (Zeneca Limited).76p.
Rhodes, M; White J. (1995) Paraquat Dichloride; Overview of the Worker
Exposure Study during Reentry into Parqaut-Treated Cotton Fields: Lab
Project number: RRA/MER/95/0418. Unpublished study prepeared by
Zeneca Ag Products. 8 p.
199
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BIBLIOGRAPHY
MRID
CITATION
43618202 Iwata, T; Findlay, M. (1995) Worker Exposure During Re-Entry into
Paraquat Treated Cotton Fields; Biological Monitoring in Georgia in 1994:
Lab project number: PARA/94/RP/01: RR/95/010B. Unpublished study
prepared by Zeneca Ag Products; Zeneca Agrochemicals, 59 p.
43644202 Meier, D. (1995) Paraquat: Worker Exposure During Mixing, Loading, and
Application of Gramoxone Extra to Pecans Using Vehicle Mounted, Ground
Boom Equipment: Lab project number: PALRA-94-AE-01: RR-019B:
CTL/P/4588. Unpublished study prepared by Zeneca Ag Products; Zeneca
Agrochemicals, 104 p.
43685001 Duerden, L. (1994) Paraquat Dichloride Technical Concentrate: Acute Oral
Toxicity to the Rat. Zeneca Central Toxicology Laboratory, UK; Report No.
CTL/P/4424.
43685002 Duerden, L. (1994) Paraquat Dichloride Ltechnical Concentrate: Acute
Dermal Toxicity to the Rat: Lab Project Number: CTL/P/4412: CR3130.
Unpublished study prepared by Zeneca Central Toxicology Lab. 45p.
43685003 Bugg, L. (1994) Paraquat Dichloride Technical Concentrate: Eye Irritation
to the Rabbit: Lab Project Number: CTL/P/4566: FB5012. Unpublished
study prepared by Zeneca Central Toxicology Lab. 35p.
43685004 Duerden, L. (1994) Paraquat Dichloride Technical Concentrate: Skin
Irritation to the Rabbit. Zeneca Central Toxicology Laboratory, UK; Report
No.CTL/P/4411.
43685005 Duerden, L. (1994) Paraquat Dichloride Technical Concentrate: Skin
Sensitization to the Guinea Pig. Zeneca Central Toxicology Laboratory,
UK; Report No.CTL/P/4460.
43954002 Grout, S. (1996) Representative Spectra from the Radiovalidation Study:
(Paraquat Dichloride): Lab Project Number: RAM/001/02. Unpublished
study prepared by Zeneca Agrochemicals. 15p.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
GENERIC AND PRODUCT SPECIFIC
DATA CALL-IN NOTICE
CERTIFIED MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the active
ingredient identified in Attachment A of this Notice, the Data Call-In Chemical Status Sheet.
to submit certain data as noted herein to the U.S. Environmental Protection Agency (EPA, the
Agency). These data are necessary to maintain the continued registration of your product(s)
containing this active ingredient. Within 90 days after you receive this Notice you must
respond as set forth in Section III below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its Attachments
1 through 7; or
2. Why you believe you are exempt from the requirements listed in this Notice and in
Attachment 3 (for both generic and product specific data), the Requirements Status and
Registrant's Response Form, (see section III-B); or
3. Why you believe EPA should not require your submission of data in the manner
specified by this Notice (see section III-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply with
its requirements or should be exempt or excused from doing so, then the registration of your
product(s) subject to this Notice will be subject to suspension. We have provided a list of all
of your products subject to this Notice in Attachment 2. All products are listed on both the
generic and product specific Data Call-In Response Forms. Also included is a list of all
registrants who were sent this Notice (Attachment 5).
The authority for this Notice is section 3(c)(2)(B) of the Federal Insecticide, Fungicide and
Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
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information is authorized under the Paperwork Reduction Act by OMB Approval No.
2070-0107 and 2070-0057 (expiration date 3-31-99).
This Notice is divided into six sections and seven Attachments. The Notice itself contains
information and instructions applicable to all Data Call-In Notices. The Attachments contain
specific chemical information and instructions. The six sections of the Notice are:
Section I - Why You are Receiving this Notice
Section II - Data Required by this Notice
Section III - Compliance with Requirements of this Notice
Section IV - Consequences of Failure to Comply with this Notice
Section V - Registrants' Obligation to Report Possible Unreasonable Adverse Effects
Section VI - Inquiries and Responses to this Notice
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet
2 - Generic Data Call-In and Product Specific Data Call-In Response Forms with
Instructions (Form A)
3- Generic Data Call-In and Product Specific Data Call-In Requirements Status and
Registrant's Response Forms with Instructions (Form B)
4- EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5- List of Registrants Receiving This Notice
6- Cost Share and Data Compensation Forms
SECTION!. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient(s) and reevaluated the
data needed to support continued registration of the subject active ingredient(s). This
reevaluation identified additional data necessary to assess the health and safety of the
continued use of products containing this active ingredient(s). You have been sent this Notice
because you have product(s) containing the subject active ingredients.
SECTION H. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
The data required by this Notice are specified in the Requirements Status and Registrant's
Response Forms: Attachment 3 (for both generic and product specific data requirements).
Depending on the results of the studies required in this Notice, additional studies/testing may
be required.
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II-B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements specified in
the Requirements Status and Registrant's Response Forms (Attachment 3) within the
timeframes provided.
II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test standards
outlined in the Pesticide Assessment Guidelines for those studies for which guidelines have
been established.
These EPA Guidelines are available from the National Technical Information Service
(NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (Telephone number:
703-487-4650).
Protocols approved by the Organization for Economic Cooperation and Development
(OECD) are also acceptable if the OECD recommended test standards conform to those
specified in the Pesticide Data Requirements regulation (40 CFR ง 158.70). When using the
OECD protocols, they should be modified as appropriate so that the data generated by the
study will satisfy the requirements of 40 CFR ง 158. Normally, the Agency will not extend
deadlines for complying with data requirements when the studies were not conducted in
accordance with acceptable standards. The OECD protocols are available from OECD, 2001
L Street, N.W., Washington, D.C. 20036 (Telephone number 202-785-6323; Fax telephone
number 202-785-0350).
All new studies and proposed protocols submitted in response to this Data Call-in Notice
must be in accordance with Good Laboratory Practices [40 CFR Part 160].
H-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3fcฅ21fB1 NOTICES ISSUED
BY THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in any way supersede or change
the requirements of any previous Data Call-In(sX or any other agreements entered into with
the Agency pertaining to such prior Notice. Registrants must comply with the requirements of
all Notices to avoid issuance of a Notice of Intent to Suspend their affected products.
SECTION HI. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
You must use the correct forms and instructions when completing your response to this
Notice. The type of Data Call-In you must comply with (Generic or Product Specific) is
specified in item number 3 on the four Data Call-In forms (Attachments 2 and 3).
III-A. SCHEDULE FOR RESPONDING TO THE AGENCY
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The appropriate responses initially required by this Notice for generic and product specific
data must be submitted to the Agency within 90 days after your receipt of this Notice. Failure
to adequately respond to this Notice within 90 days of your receipt will be a basis for issuing
a Notice of Intent to Suspend (NOIS) affecting your products. This and other bases for
issuance of NOIS due to failure to comply with this Notice are presented in Section IV-A and
IV-B.
III-B. OPTIONS FOR RESPONDING TO THE AGENCY
1. Generic Data Requirements
The options for responding to this Notice for generic data requirements are: (a) voluntary
cancellation, (b) delete use(s), (c) claim generic data exemption, (d) agree to satisfy the
generic data requirements imposed by this Notice or (e) request a data waiver(s).
A discussion of how to respond if you choose the Voluntary Cancellation option, the
Delete Use(s) option or the Generic Data Exemption option is presented below. A discussion
of the various options available for satisfying the generic data requirements of this Notice is
contained in Section III-C. A discussion of options relating to requests for data waivers is
contained in Section III-D.
Two forms apply to generic data requirements, one or both of which must be used in
responding to the Agency, depending upon your response. These two forms are the
Data-Call-in Response Form, and the Requirements Status and Registrant's Response Form.
(contained in Attachments 2 and 3, respectively).
The Data Call-In Response Forms must be submitted as part of every response to this
Notice. The Requirements Status and Registrant's Response Forms also must be submitted if
you do not qualify for a Generic Data Exemption or are not requesting voluntary cancellation
of your registration(s). Please note that the company's authorized representative is required to
sign the first page of both Data Call-In Response Forms and the Requirements Status and
Registrant's Response Forms (if this form is required) and initial any subsequent pages. The
forms contain separate detailed instructions on the response options. Do not alter the printed
material. If you have questions or need assistance in preparing your response, call or write the
contact person(s) identified in Attachment 1.
a. Voluntary Cancellation -
You may avoid the requirements of this Notice by requesting voluntary cancellation of
your produces) containing the active ingredient that is the subject of this Notice. If you wish
to voluntarily cancel your product, you must submit completed Generic and Product Specific
Data Call-in Response Forms (Attachment 2), indicating your election of this option.
Voluntary cancellation is item number 5 on both Data Call-In Response Form(s). If you
choose this option, these are the only forms that you are required to complete.
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If you chose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice, which are contained in Section IV-C.
b. Use Deletion -
You may avoid the requirements of this Notice by eliminating the uses of your product to
which the requirements apply. If you wish to amend your registration to delete uses, you must
submit the Requirements Status and Registrant's Response Form (Attachment 3), a completed
application for amendment, a copy of your proposed amended labeling, and all other
information required for processing the application. Use deletion is option number 7 under
item 9 in the instructions for the Requirements Status and Registrant's Response Forms. You
must also complete a Data Call-In Response Form by signing the certification, item number 8.
Application forms for amending registrations may be obtained from the Registration Support
Branch, Registration Division, Office of Pesticide Programs, EPA, by calling (703) 308-8358.
If you choose to delete the use(s) subject to this Notice or uses subject to specific data
requirements, further sale, distribution, or use of your product after one. year from the due date
of your 90 day response, is allowed only if the product bears an amended label.
c. Generic Data Exemption -
Under section 3(c)(2)(D) of FIFRA, an applicant for registration of a product is exempt
from the requirement to submit or cite generic data concerning an active ingredient if the
active ingredient in the product is derived exclusively from purchased, registered pesticide
products containing the active ingredient. EPA has concluded, as an exercise of its discretion,
that it normally will not suspend the registration of a product which would qualify and
continue to qualify for the generic data exemption in section 3(c)(2)(D) of FIFRA. To qualify,
all of the following requirements must be met:
(i). The active ingredient in your registered product must be present solely because of
incorporation of another registered product which contains the subject active ingredient
and is purchased from a source not connected with you;
(ii). Every registrant who is the ultimate source of the active ingredient in your product
subject to this DCI must be in compliance with the requirements of this Notice and must
remain in compliance; and
(iii). You must have provided to EPA an accurate and current "Confidential Statement of
Formula" for each of your products to which this Notice applies.
To apply for the Generic Data Exemption you must submit a completed Data Call-In
Response Form. Attachment 2 and all supporting documentation. The Generic Data
Exemption is item number 6a on the Data Call-In Response Form. If you claim a generic data
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exemption you are not required to complete the Requirements Status and Registrant's
Response Form. Generic Data Exemption cannot be selected as an option for responding to
product specific data requirements.
If you are granted a Generic Data Exemption, you rely on the efforts of other persons to
provide the Agency with the required data. If the registrant(s) who have committed to
generate and submit the required data fail to take appropriate steps to meet requirements or
are no longer in compliance with this Data Call-In Notice, the Agency will consider that both
they and you are not compliance and will normally initiate proceedings to suspend the
registrations of both your and their product(s), unless you commit to submit and do submit the
required data within the specified time. In such cases the Agency generally will not grant a
time extension for submitting the data.
d. Satisfying the Generic Data Requirements of this Notice
There are various options available to satisfy the generic data requirements of this Notice.
These options are discussed in Section III-C.l. of this Notice and comprise options 1 through
6 of item 9 in the instructions for the Requirements Status and Registrant's Response Form
and item 6b on the Data Call-In Response Form. If you choose item 6b (agree to satisfy the
generic data requirements), you must submit the Data Call-in Response Form and the
Requirements Status and Registrant's Response Form as well as any other information/data
pertaining to the option chosen to address the data requirement. Your response must be on
the forms marked "GENERIC" in item number 3.
e. Request for Generic Data Waivers.
Waivers for generic data are discussed in Section III-D.l. of this Notice and are covered by
options 8 and 9 of item 9 in the instructions for the Requirements Status and Registrant's
Response Form. If you choose one of these options, you must submit both forms as well as
any other information/data pertaining to the option chosen to address the data requirement.
2. Product Specific Data Requirements
The options for responding to this Notice for product specific data ar,e: (a) voluntary
cancellation, (b) agree to satisfy the product specific data requirements imposed by this
Notice or (c) request a data waiver(s).
A discussion of how to respond if you choose the Voluntary Cancellation option is
presented below. A discussion of the various options available for satisfying the product
specific data requirements of this Notice is contained in Section III-C.2. A discussion of
options relating to requests for data waivers is contained in Section III-D.2.
Two forms apply to the product specific data requirements one or both of which must be
used in responding to the Agency, depending upon your response. These forms are the
Data-Call-in Response Form, and the Requirements Status and Registrant's Response Form.
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for product specific data (contained in Attachments 2 and 3, respectively). The Data Call-In
Response Form must be submitted as part of every response to this Notice. In addition, one
copy of the Requirements Status and Registrant's Response Form also must be submitted for
each product listed on the Data Call-In Response Form unless the voluntary cancellation
option is selected. Please note that the company's authorized representative is required to sign
the first page of the Data Call-in Response Form and Requirements Status and Registrant's
Response Form (if this form is required) and initial any subsequent pages. The forms contain
separate detailed instructions on the response options. Do not alter the printed material. If you
have questions or need assistance in preparing your response, call or write the contact
person(s) identified in Attachment 1.
a. Voluntary Cancellation
You may avoid the requirements of this Notice by requesting voluntary cancellation of
your product(s) containing the active ingredient that is the subject of this Notice. If you wish
to voluntarily cancel your product, you must submit a completed Data Call-In Response
Form< indicating your election of this option. Voluntary cancellation is item number 5 on both
the Generic and Product Specific Data Call-in Response Forms. If you choose this
option, you must complete both Data Call-in response forms. These are the only forms that
you are required to complete.
If you choose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice which are contained in Section IV-C.
b- Satisfying the Product Specific Data Requirements of this Notice..
There are various options available to satisfy the product specific data requirements of this
Notice. These options are discussed in Section III-C.2. of this Notice and comprise options 1
through 6 of item 9 in the instructions for the product specific Requirements Status and
Registrant's Response Form and item numbers 7a and 7b (agree to satisfy the product specific
data requirements for an MUP or EUP as applicable) on the product specific Data Call-in
Response Form. Note that the options available for addressing product specific data
requirements differ slightly from those options for fulfilling generic data requirements.
Deletion of a use(s) and the low volume/minor use option are not valid options for fulfilling
product specific data requirements. It is important to ensure that you are using the correct
forms and instructions when completing your response to the Reregistration Eligibility
Decision document.
c. Request for Product Specific Data Waivers.
Waivers for product specific data are discussed in Section III-D.2. of this Notice and are
covered by option 7 of item 9 in the instructions for the Requirements Status and Registrant's
Response Form. If you choose this option, you must submit the Data Call-in Response Form
and the Requirements Status and Registrant's Response Form as well as any other
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information/data pertaining to the option chosen to address the data requirement. Your
response must be on the forms marked "PRODUCT SPECIFIC" in item number 3.
III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
1. Generic Data
If you acknowledge on the Generic Data Call-In Response Form that you agree to satisfy
the generic data requirements (i.e. you select item number 6b), then you must select one of the
six options on the Generic Requirements Status and Registrant's Response Form related to
data production for each data requirement. Your option selection should be entered under
item number 9, "Registrant Response." The six options related to data production are the first
six options discussed under item 9 in the instructions for completing the Requirements Status
and Registrant's Response Form. These six options are listed
immediately below with information in parentheses to guide you to additional instructions
provided hi this Section. The options are:
(1) I will generate and submit data within the specified timeframe '(Developing Data)
(2) I have entered into an agreement with one or more registrants to develop data jointly
(Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing
study that has been submitted but not reviewed by the Agency (Citing an Existing
Study)
Option 1. Developing Data
If you choose to develop the required data it must be in conformance with Agency
deadlines and with other Agency requirements as referenced herein and in the attachments.
All data generated and submitted must comply with the Good Laboratory Practice (GLP) rule
(40 CFR Part 160), be conducted according to the Pesticide Assessment Guidelines (PAG)
and be in conformance with the requirements of PR Notice 86-5. In addition, certain studies
require Agency approval of test protocols in advance of study initiation. Those studies for
which a protocol must be submitted have been identified in the Requirements Status and
Registrant's Response Form and/or footnotes to the form. If you wish to use a protocol which
differs from the options discussed in Section II-C of this Notice, you must submit a detailed
description of the proposed protocol and your reason for wishing to use it. The Agency may
choose to reject a protocol not specified in Section II-C. If the Agency rejects your protocol
you will be notified in writing, however, you should be aware that rejection of a proposed
protocol will not be a basis for extending the deadline for submission of data.
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A progress report must be submitted for each study within 90 days from the date you are
required to commit to generate or undertake some other means to address that study
requirement, such as making an offer to cost share or agreeing to share in the cost of
developing that study. This 90-day progress report must include the date the study was or
will be initiated and, for studies to be started within 12 months of commitment, the name and
address of the laboratory(ies) or individuals who are or will be conducting the study.
In addition, if the time frame for submission of a final report is more than 1 year, interim
reports must be submitted at 12 month intervals from the date you are required to commit to
generate or otherwise address the requirement for the study. In addition to the other
information specified in the preceding paragraph, at a minimum, a brief description of current
activity on and the status of the study must be included as well as a full
description of any problems encountered since the last progress report.
The time frames in the Requirements Status and Registrant's Response Form are the time
frames that the Agency is allowing for the submission of completed study reports or
protocols. The noted deadlines run from the date of the receipt of this Notice by the registrant.
If the data are not submitted by the deadline, each registrant is subject to receipt of a Notice of
Intent to Suspend the affected registration(s).
If you cannot submit the data/reports to the Agency in the time required by this Notice and
intend to seek additional time to meet the requirements(s), you must submit a request to the
Agency which includes: (1) a detailed description of the expected difficulty and (2) a
proposed schedule including alternative dates for meeting such requirements on a step-by-step
basis. You must explain any technical or laboratory difficulties and provide documentation
from the laboratory performing the testing. While EPA is considering your request, the
original deadline remains. The Agency will respond to your request in writing. If EPA does
not grant your request, the original deadline remains. Normally, extensions can be requested
only in cases of extraordinary testing problems beyond the expectation or control of the
registrant. Extensions will not be given in submitting the 90-day responses. Extensions will
not be considered if the request for extension is not made in a timely fashion; in no event shall
an extension request be considered if it is submitted at or after the lapse of the subject
deadline.
Option 2. Agreement to Share in Cost to Develop Data
If you choose to enter into an agreement to share in the cost of producing the required data
but will not be submitting the data yourself, you must provide the name of the registrant who
will be submitting the data. You must also provide EPA with documentary evidence that an
agreement has been formed. Such evidence may be your letter offering to join in an
agreement and the other registrant's acceptance of your offer, or a written statement by the
parties that an agreement exists. The agreement to produce the data need not specify all of the
terms of the final arrangement between the parties or the mechanism to resolve the terms.
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Section 3(c)(2)(B) provides that if the parties cannot resolve the terms of the agreement they
may resolve their differences through binding arbitration.
Option 3. Offer to Share in the Cost of Data Development
If you have made an offer to pay in an attempt to enter into an agreement or amend an
existing agreement to meet the requirements of this Notice and have been unsuccessful, you
may request EPA (by selecting this option) to exercise its discretion not to suspend your
registration(s), although you do not comply with the data submission requirements of this
Notice. EPA has determined that as a general policy, absent other relevant considerations, it
will not suspend the registration of a product of a registrant who has in good faith sought and
continues to seek to enter into a joint data development/cost sharing program, but the other
registrant(s) developing the data has refused to accept the offer. To qualify for this option,
you must submit documentation to the Agency proving that you have made an offer to
another registrant (who has an obligation to submit data) to share in the burden of developing
that data. You must also submit to the Agency a completed EPA Form 8570-32, Certification
of Offer to Cost Share hi the Development of Data, Attachment 7. In addition, you must
demonstrate that the other registrant to whom the offer was made has not accepted your offer
to enter into a cost-sharing agreement by including a copy of your offer and proof of the other
registrant's receipt of that offer (such as a certified mail receipt). Your offer must, in addition
to anything else, offer to share in the burden of producing the data upon terms to be agreed to
or, failing agreement, to be bound by binding arbitration as provided by FIFRA section
3(c)(2)(B)(iii) and must not qualify this offer. The other registrant must also inform EPA of its
election of an option to develop and submit the data required by this Notice by submitting a
Data Call-In Response Form and a Requirements Status and Registrant's Response Form
committing to develop and submit the data required by this Notice.
In order for you to avoid suspension under this option, you may not withdraw your offer to
share in the burden of developing the data. In addition, the other registrant must fulfill its
commitment to develop and submit the data as required by this Notice. If the other registrant
fails to develop the data or for some other reason is subject to suspension, your registration as
well as that of the other registrant normally will be subject to initiation of suspension
proceedings, unless you commit to submit, and do submit, the required data in the specified
tune frame. In such cases, the Agency generally will not grant a time extension for submitting
the data.
Option 4. Submitting an Existing Study
If you choose to submit an existing study in response to this Notice, you must determine
that the study satisfies the requirements imposed by this Notice. You may only submit a study
that has not been previously submitted to the Agency or previously cited by anyone. Existing
studies are studies which predate issuance of this Notice. Do not use this option if you are
submitting data to upgrade a study. (See Option 5).
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You should be aware that if the Agency determines that the study is not acceptable, the
Agency will require you to comply with this Notice, normally without an extension of the
required date of submission. The Agency may determine at any time that a study is not valid
and needs to be repeated.
To meet the requirements of the DCI Notice for submitting an existing study, all of the
following three criteria must be clearly Met:
a. You must certify at the time that the existing study is submitted that the raw data and
specimens from the study are available for audit and review and you must identify
where they are available. This must be done in accordance with the requirements of the
Good Laboratory Practice (GLP) regulation, 40 CFR Part 160. As stated in 40 CFR
160.3 'Raw data' means any laboratory worksheets, records, memoranda, notes, or exact
copies thereof, that are the result of original observations and activities of a study and
are necessary for the reconstruction and evaluation of the report of that study. In the
event that exact transcripts of raw data have been prepared (e.g., tapes which have been
transcribed verbatim, dated, and verified accurate by signature), the exact copy or exact
transcript may be substituted for the original source as raw data. 'Raw data' may include
photographs, microfilm or microfiche copies, computer printouts, magnetic media,
including dictated observations, and recorded data from automated instruments." The
term "specimens", according to 40 CFR 160.3, means "any material derived from a test
system for examination or analysis."
b. Health and safety studies completed after May 1984 also must also contain all
GLP-required quality assurance and quality control information, pursuant to the
requirements of 40 CFR Part 160. Registrants also must certify at'the time of submitting
the existing study that such GLP information is available for post May 1984 studies by
including an appropriate statement on or attached to the study signed by an authorized
official or representative of the registrant.
c. You must certify that each study fulfills the acceptance criteria for the Guideline
relevant to the study provided in the FIFRA Accelerated Reregistration Phase 3
Technical Guidance and that the study has been conducted according to the Pesticide
Assessment Guidelines (PAG) or meets the purpose of the PAG (both available from
NTIS). A study not conducted according to the PAG may be submitted to the Agency
for consideration if the registrant believes that the study clearly meets the purpose of the
PAG. The registrant is referred to 40 CFR 158.70 which states the Agency's policy
regarding acceptable protocols. If you wish to submit the study, you must, in addition to
certifying that the purposes of the PAG are met by the study, clearly articulate the
rationale why you believe the study meets the purpose of the PAG, including copies of
any supporting information or data. It has been the Agency's experience that studies
completed prior to January 1970 rarely satisfied the purpose of the PAG and that
necessary raw data usually are not available for such studies.
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If you submit an existing study, you must certify that the study meets all requirements of
the criteria outlined above.
If EPA has previously reviewed a protocol for a study you are submitting, you must
identify any action taken by the Agency on the protocol and must indicate, as part of your
certification, the manner in which all Agency comments, concerns, or issues were addressed
in the final protocol and study.
If you know of a study pertaining to any requirement in this Notice which does not meet
the criteria outlined above but does contain factual information regarding unreasonable
adverse effects, you must notify the Agency of such a study. If such study is in the Agency's
files, you need only cite it along with the notification. If not in the Agency's files, you must
submit a summary and copies as required by PR Notice 86-5.
Option 5. Upgrading a Study
If a study has been classified as partially acceptable and upgradeable, you may submit data
to upgrade that study. The Agency will review the data submitted and determine if the
requirement is satisfied. If the Agency decides the requirement is not satisfied, you may still
be required to submit new data normally without any time extension. Deficient, but
upgradeable studies will normally be classified as supplemental. However, it is important to
note that not all studies classified as supplemental are upgradeable. If you have questions
regarding the classification of a study or whether a study may be upgraded, call or write the
contact person listed in Attachment 1. If you submit data to upgrade an existing study you
must satisfy or supply information to correct ajl deficiencies in the study identified by EPA.
You must provide a clearly articulated rationale of how the deficiencies have been remedied
or corrected and why the study should be rated as acceptable to EPA. Your submission must
also specify the MRID number(s) of the study which you are attempting to upgrade and must
be in conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study classified as
unacceptable and determined by the Agency as not capable of being upgraded.
This option also should be used to cite data that has been previously submitted to upgrade
a study, but has not yet been reviewed by the Agency. You must provide the MRID number
of the data submission as well as the MRID number of the study being upgraded.
The criteria for submitting an existing study, as specified in Option 4 above, apply to all
data submissions intended to upgrade studies. Additionally, your submission of data intended
to upgrade studies must be accompanied by a certification that you comply with each of those
criteria, as well as a certification regarding protocol compliance with Agency
requirements.
Option 6. Citing Existing Studies
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If you choose to cite a study that has been previously submitted to EPA, that study must
have been previously classified by EPA as acceptable, or it must be a study which has not yet
been reviewed by the Agency. Acceptable toxicology studies generally will have been
classified as "core-guideline" or "core-minimum." For ecological effects studies, the
classification generally would be a rating of "core." For all other disciplines the classification
would be "acceptable." With respect to any studies for which you wish to select this option,
you must provide the. MRID number of the study you are citing and, if the study has been
reviewed by the Agency, you must provide the Agency's classification of the study.
If you are citing a study of which you are not the original data submitter, you must submit
a completed copy of EPA Form 8570-31, Certification with Respect to Data Compensation
Requirements.
2. Product Specific Data
If you acknowledge on the product specific Data Call-In Response Form that you agree to
satisfy the product specific data requirements (i.e. you select option 7a or 7b), then you must
select one of the six options on the Requirements Status and Registrant's Response Form
related to data production for each data requirement. Your option selection should be entered
under item number 9, "Registrant Response." The six options related to data production are
the first six options discussed under item 9 hi the instructions for completing the
Requirements Status and Registrant's Response Form. These six options are listed
immediately below with information in parentheses to guide registrants to additional
instructions provided in this Section. The options are:
(1) I will generate and submit data within the specified time-frame (Developing Data)
(2) I have entered into an agreement with one or more registrants to develop data jointly
(Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing
study that has been
submitted but not reviewed by the Agency (Citing an Existing Study)
Option 1. Developing Data The requirements for developing product specific data are the
same as those described for generic data (see Section III.C.l, Option 1) except that normally
no protocols or progress reports are required.
Option 2. Agree to Share in Cost to Develop Data If you enter into an agreement to cost
share, the same requirements apply to product specific data as to generic data (see Section
III.C.l, Option 2). However, registrants may only choose this option for acute toxicity data
and certain efficacy data and only if EPA has indicated in the attached data tables that your
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product and at least one other product are similar for purposes of depending on
the same data. If this is the case, data may be generated for just one of the products in the
group. The registration number of the product for which data will be submitted must be noted
in the agreement to cost share by the registrant selecting this option.
Option 3. Offer to Share in the Cost of Data Development The same requirements for
generic data (Section IILC.I., Option 3) apply to this option. This option only applies to acute
toxicity and certain efficacy data as described in option 2 above.
Option 4. Submitting an Existing Study The same requirements described for generic data
(see Section in.C.l., Option 4) apply to this option for product specific data.
Option 5. Upgrading a Study -- The same requirements described for generic data (see
Section IILC.I., Option 5) apply to this option for product specific data.
Option 6. Citing Existing Studies The same requirements described for generic data (see
Section IILC.I., Option 6) apply to this option for product specific data".
Registrants who select one of the above 6 options must meet all of the requirements
described in the instructions for completing the Data Call-In Response Form and the
Requirements Status and Registrant's Response Form, and in the generic data requirements
section (in.C.l.). as appropriate.
III-D REQUESTS FOR DATA WAIVERS
1. Generic Data
There are two types of data waiver responses to this Notice. The first is a request for a low
volume/minor use waiver and the second is a waiver request based on your belief that the data
requirements) are not appropriate for your product.
a. Low Volume/Minor Use Waiver
Option 8 under item 9 on the Requirements Status and Registrant's Response Form.
Section 3(c)(2)(A) of FIFRA requires EPA to consider the appropriateness of requiring
data for low volume, minor use pesticides. In implementing this provision, EPA considers
low volume pesticides to be only those active ingredients whose total
production volume for all pesticide registrants is small. In determining whether to grant a low
volume, minor use waiver, the Agency will consider the extent, pattern and volume of use, the
economic incentive to conduct the testing, the importance of the pesticide, and the exposure
and risk from use of the pesticide. If an active ingredient is used for both high volume and
low volume uses, a low volume exemption will not be approved. If all uses of an active
ingredient are low volume and the combined volumes for all uses are also low, then an
exemption may be granted, depending on review of other information outlined below. An
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exemption will not be granted if any registrant of the active ingredient elects to conduct the
testing. Any registrant receiving a low volume minor use waiver must remain within the sales
figures in their forecast supporting the waiver request in order to remain qualified for such
waiver. If granted a waiver, a registrant will be required, as a condition of the waiver, to
submit annual sales reports. The Agency will respond to requests for waivers in writing.
To apply for a low volume, minor use waiver, you must submit the following
information, as applicable to your product(s), as part of your 90-day response to this
Notice:
(i). Total company sales (pounds and dollars) of all registered product(s) containing the
active ingredient. If applicable to the active ingredient, include foreign sales for those
products that are not registered in this country but are applied to sugar (cane or beet),
coffee, bananas, cocoa, and other such crops. Present the above information by year for
each of the past five years.
(ii) Provide an estimate of the sales (pounds and dollars) of the active ingredient for
each major use site. Present the above information by year for each of the past five years.
(iii) Total direct production cost of product(s) containing the active ingredient by year
for the past five years. Include information on raw material cost, direct labor cost,
advertising, sales and marketing, and any other significant costs listed separately.
(iv) Total indirect production cost (e.g. plant overhead, amortized plant and equipment)
charged to product(s) containing the active ingredient by year for the past five years.
Exclude all non-recurring costs that were directly related to the active ingredient, such as
costs of initial registration and any data development.
(v) A list of each data requirement for which you seek a waiver. Indicate the type of
waiver sought and the estimated cost to you (listed separately for each data requirement
and associated test) of conducting the testing needed to fulfill each of these data
requirements.
(vi) A list of each data requirement for which you are not seeking any waiver and the
estimated cost to you (listed separately for each data requirement and associated test) of
conducting the testing needed to fulfill each of these data requirements.
(vii) For each of the next ten years, a year-by-year forecast of company sales (pounds
and dollars) of the active ingredient, direct production costs of product(s) containing the
active ingredient (following the parameters in item 2 above), indirect production costs of
produces) containing the active ingredient (following the parameters in item 3 above), and
costs of data development pertaining to the active ingredient.
(viii) A description of the importance and unique benefits of the active ingredient to
users. Discuss the use patterns and the effectiveness of the active ingredient relative to
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registered alternative chemicals and non-chemical control strategies. Focus on benefits
unique to the active ingredient, providing information that is as quantitative as possible. If
you do not have quantitative data upon which to base your estimates, then present the
reasoning used to derive your estimates. To assist the Agency in determining the degree of
importance of the active ingredient in terms of its benefits, you should provide information
on any of the following factors, as applicable to your produces): (a) documentation of the
usefulness of the active ingredient in Integrated Pest Management, (b) description of the
beneficial impacts on the environment of use of the active ingredient, as opposed to its
registered alternatives, (c) information on the breakdown of the active ingredient after use
and on its persistence in the environment, and (d) description of its usefulness against a
pest(s) of public health significance.
Failure to submit sufficient information for the Agency to make a determination
regarding a request for a low volume/minor use waiver will result in denial of the request
for a waiver.
b. Request for Waiver of Data
Option 9, under Item 9, on the Requirements Status and Registrant's Response Form.
This option may be used if you believe that a particular data requirement should not apply
because the requirement is inappropriate. You must submit a rationale explaining why you
believe the data requirements should not apply. You also must submit the current label(s)
of your product(s) and, if a current copy of your Confidential Statement of Formula is not
already on file you must submit a current copy.
You will be informed of the Agency's decision in writing. If the Agency determines that
the data requirements of this Notice are not appropriate to your product(s), you will not be
required to supply the data pursuant to section 3(c)(2)(B). If EPA determines that the data
are required for vour productfsX you must choose a method of meeting the requirements of
this Notice within the time frame provided by this Notice. Within 30 days of your receipt
of the Agency's written decision, you must submit a revised Requirements Status and
Registrant's Response Form indicating the option chosen.
2. Product Specific Data
If you request a waiver for product specific data because you believe it is inappropriate,
you must attach a complete justification for the request including technical reasons, data
and references to relevant EPA regulations, guidelines or policies. (Note: any supplemental
data must be submitted in the format required by PR Notice 86-5). This will be the only
opportunity to state the reasons or provide information in support of your request. If the
Agency approves your waiver request, you will not be required to supply the data pursuant
to section 3(c)(2)(B) of FIFRA. If the Agency denies your waiver request, you must choose
an option for meeting the data requirements of this Notice within 30 days of the receipt of
the Agency's decision. You must indicate and submit the option chosen on the product
specific Requirements Status and Registrant's Response Form. Product specific data
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requirements for product chemistry, acute toxicity and efficacy (where appropriate) are
required for all products and the Agency would grant a waiver only under extraordinary
circumstances. You should also be aware that submitting a waiver request will not
automatically extend the due date for the study in question. Waiver requests submitted
without adequate supporting rationale will be denied and the original due date will remain
in force.
SECTION IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE
IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice due to
failure by a registrant to comply with the requirements of this Data Call-In Notice, pursuant to
FIFRA section 3(c)(2)(B). Events which may be the basis for issuance of a Notice of Intent to
Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt of this
Notice.
2. Failure to submit on the required schedule an acceptable proposed or final protocol
when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on a study as
required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by this Notice.
5. Failure to take a required action or submit adequate information pertaining to any option
chosen to address the data requirements (e.g., any required action or information
pertaining to submission or citation of existing studies or offers, arrangements, or
arbitration on the sharing of costs or the formation of Task Forces, failure to comply
with the terms of an agreement or arbitration concerning joint data development or
failure to comply with any terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of submitted studies, as
required by Section III-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
8. Failure of the registrant to whom you have tendered an offer to share in the cost of
developing data and provided proof of the registrant's receipt of such offer or failure of
a registrant on whom you rely for a generic data exemption either to:
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i. Inform EPA of intent to develop and submit the data required by this Notice on a
Data Call-In Response Form and a Requirements Status and Registrant's Response
Form.
ii. Fulfill the commitment to develop and submit the data as required by this Notice; or
iii. Otherwise take appropriate steps to meet the requirements stated in this Notice,
unless you commit to submit and do submit the required data in the specified time
frame.
9. Failure to take any required or appropriate steps, not mentioned above, at any time
following the issuance of this Notice.
IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS
UNACCEPTABLE
The Agency may determine that a study (even if submitted within the required time) is
unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The
grounds for suspension include, but are not limited to, failure to meet any of the following:
1) EPA requirements specified in the Data Call-In Notice or other documents incorporated
by reference (including, as applicable, EPA Pesticide Assessment Guidelines, Data
Reporting Guidelines, and GeneTox Health Effects Test Guidelines) regarding the design,
conduct, and reporting of required studies. Such requirements include, but are not limited
to, those relating to test material, test procedures, selection of species, number of animals,
sex and distribution of animals, dose and effect levels to be tested or attained, duration of
test, and, as applicable, Good Laboratory Practices.
2) EPA requirements regarding the submission of protocols, including the incorporation of
any changes required by the Agency following review.
3) EPA requirements regarding the reporting of data, including the manner of reporting,
the completeness of results, and the adequacy of any required supporting (or raw) data,
including, but not limited to, requirements referenced or included in this Notice or
contained in PR 86-5. All studies must be submitted in the form of a final report; a
preliminary report will not be considered to fulfill the submission requirement.
IV-C EXISTING STOCKS OF SUSPENDED OR CANCELLED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing stocks
of a pesticide product which has been suspended or cancelled if doing so would be consistent
with the purposes of the Act.
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The Agency has determined that such disposition by registrants of existing stocks for a
suspended registration when a section 3(c)(2)(B) data request is outstanding generally would
not be consistent with the Act's purposes. Accordingly, the Agency anticipates granting
registrants permission to sell, distribute, or use existing stocks of suspended product(s) only in
exceptional circumstances. If you believe such disposition of existing stocks of your
product(s) which may be suspended for failure to comply with this Notice should be
permitted, you have the burden of clearly demonstrating to EPA that granting such permission
would be consistent with the Act. You also must explain why an "existing stocks" provision is
necessary, including a statement of the quantity of existing stocks and your estimate of the
time required for their sale, distribution, and use. Unless you meet this burden, the Agency
will not consider any request pertaining to the continued sale, distribution, or use of your
existing stocks after suspension.
If you request a voluntary cancellation of your product(s) as a response to this Notice and
your product is in full compliance with all Agency requirements, you will have, under most
circumstances, one year from the date your 90 day response to this Notice is due, to sell,
distribute, or use existing stocks. Normally, the Agency will allow persons other than the
registrant such as independent distributors, retailers and end users to sell, distribute or use
such existing stocks until the stocks are exhausted. Any sale, distribution or use of stocks of
voluntarily cancelled products containing an active ingredient for which the Agency has
particular risk concerns will be determined on a case-by-case basis.
Requests for voluntary cancellation received after the 90 day response period required by
this Notice will not result in the agency granting any additional time to sell, distribute, or use
existing stocks beyond a year from the date the 90 day response was due, unless you
demonstrate to the Agency that you are in full compliance with all Agency requirements,
including the requirements of this Notice. For example, if you decide to voluntarily cancel
your registration six months before a 3-year study is scheduled to be submitted, all progress
reports and other information necessary to establish that you have been conducting the study
in an acceptable and good faith manner must have been submitted to the Agency, before EPA
will consider granting an existing stocks provision.
SECTION V.
REGISTRANTS' OBLIGATION TO REPORT POSSIBLE
UNREASONABLE ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states that if at any time after a
pesticide is registered a registrant has additional factual information regarding unreasonable
adverse effects on the environment by the pesticide, the registrant shall submit the
information to the Agency. Registrants must notify the Agency of any factual information
they have, from whatever source, including but not limited to interim or preliminary results of
studies, regarding unreasonable adverse effects on man or the environment. This requirement
continues as long as the products are registered by the Agency.
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SECTION VI. PTOUERIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by this
Notice, call the contact person(s) listed in Attachment 1, the Data Call-In Chemical Status
Sheet.
All responses to this Notice must include completed Data Call-In Response Forms
(Attachment 2)and completed Requirements Status and Registrant's Response Forms
(Attachment 3), for both (generic and product specific data) and any other documents
required by this Notice, and should be submitted to the contact person(s) identified in
Attachment 1. If the voluntary cancellation or generic data exemption option is chosen, only
the Generic and Product Specific Data Call-in Response Forms need be submitted.
The Office of Compliance (OC) of the Office of Enforcement and Compliance Assurance
(OECA), EPA, will be monitoring the data being generated hi response to this Notice.
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregistration Division
Attachments
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet
2 - Generic Data Call-In and Product Specific Data Call-In Response Forms with
Instructions
3- Generic Data Call-In and Product Specific Data Call-In Requirements Status and
Registrant's Response Forms with Instructions
4- EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5- List of Registrants Receiving This Notice
6- Confidential Statement of Formula. Cost Share and Data Compensation Forms
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PARAQUAT BICHLORIDE DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have product(s)
containing Paraquat Dichloride.
This Product Specific Data Call-In Chemical Status Sheet, contains an overview of data
required by this notice, and point of contact for inquiries pertaining to the reregistration of 0262.
This attachment is to be used in conjunction with (1) the Product Specific Data Call-In Notice,
(2) the Product Specific Data Call-In Response Form (Attachment 2), (3) the Requirements Status
and Registrant's Form (Attachment 3), (4) EPA's Grouping of End-Use Products for Meeting
Acute Toxicology Data Requirement (Attachment 4), (5) the EPA Acceptance Criteria
(Attachment 5), (6) a list of registrants receiving this DCI (Attachment 6) and (7) the Cost Share
and Data Compensation Forms in replying to this 0262 Product Specific Data Call-In
(Attachment 7). Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for Paraquat Dichloride are
contained in the Requirements Status and Registrant's Response. Attachment 3. The Agency has
concluded that additional data on Paraquat Dichloride are needed for specific products. These
data are required to be submitted to the Agency within the time frame listed. These data are
needed to fully complete the reregistration of all eligible Paraquat Dichloride products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding this product specific data requirements and procedures
established by this Notice, please contact Venus Eagle at (703) 308-8045.
All responses to this Notice for the Product Specific data requirements should be submitted
to:
Venus Eagle
Chemical Review Manager Team 81
Product Reregistration Branch
Special Review and Reregistration Branch 7508W
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: PARAQUAT DICHLORIDE
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PARAQUAT BICHLORIDE DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Generic Data Call-In Notice because you have product(s) containing
Paraquat Dichloride.
This Generic Data Call-In Chemical Status Sheet, contains an overview of data required by
this notice, and point of contact for inquiries pertaining to the reregistration of Paraquat
Dichloride. This attachment is to be used in conjunction with (1) the Generic Data Call-in
Notice, (2) the Generic Data Call-In Response Form (Attachment 2), (3) the Requirements Status
and Registrant's Form (Attachment 2), (4) a list of registrants receiving this DCI (Attachment 4),
(5) the EPA Acceptance Criteria (Attachment 5), and (6) the Cost Share and Data Compensation
Forms in replying to this Paraquat Dichloride Generic Data Call In (Attachment F). Instructions
and guidance accompany each form..
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the generic database for Paraquat
Dichloride are contained in the Requirements Status and Registrant's Response. Attachment C.
The Agency has concluded that additional product chemistry data on Paraquat Dichloride are
needed. These data are needed to fully complete the reregistration of all eligible Paraquat
Dichloride products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic data requirements and procedures established
by this Notice, please contact Ruby Whiters at (703) 308-8079.
All responses to this Notice for the generic data requirements should be submitted to:
Ruby Whiters, Chemical Review Manager
Reregistration Branch
Special Review and Registration Division (H7508W)
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: PARAQUAT DICHLORIDE
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Instructions For Completing The "Data Call-in Response Forms" For The Generic And
Product Specific Data Call-In
INTRODUCTION
These instructions apply to the Generic and Product Specific "Data Call-In Response Forms"
and are to be used by registrants to respond to generic and product specific Data Call-Ins as
part of EPA's Reregistration Program under the Federal Insecticide, Fungicide, and
Rodenticide Act. If you are an end-use product registrant only and have been sent this DCI
letter as part of a RED document you have been sent just the product specific "Data Call-in
Response Forms." Only registrants responsible for generic data have been sent the generic
data response form. The type of Data Call-in (generic or product specific) is indicated in
item number 3 ("Date and Type of DCI") on each form.
Although the form is the same for both generic and product specific data, instructions for
completing these forms are different. Please read these instructions carefully before filling
out the forms.
EPA has developed these forms individually for each registrant, and has preprinted these
forms with a number of items. DO NOT use these forms for any other active ingredient.
Items 1 through 4 have been preprinted on the form. Items 5 through 7 must be completed by
the registrant as appropriate. Items 8 through 11 must be completed by the registrant before
submitting a response to the Agency.
The public reporting burden for this collection of information is estimated to average 15
minutes per response, including time for reviewing instructions, searching existing data
sources, gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding the burden estimate or any other aspect
of this collection of information, including suggestions for reducing this burden, to Chief,
Information Policy Branch, Mail Code 2136, U.S. Environmental Protection Agency, 401 M
St., S.W., Washington, D.C. 20460; and to the Office of Management and Budget, Paperwork
Reduction Project 2070-0107, Washington, D.C. 20503.
223
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
Generic and Product Specific Data Call-In
Item 1. ON BOTH FORMS: This item identifies your company name, number and address.
Item 2. ON BOTH FORMS: This item identifies the case number, case name, EPA
chemical number and chemical name.
ItemS. ON BOTH FORMS: This item identifies the type of Data Call-In. The date of
issuance is date stamped.
Item 4. ON BOTH FORMS: This item identifies the EPA product registrations relevant to
the data call-in. Please note that you are also responsible for informing the Agency
of your response regarding any product that you believe may be covered by this Data
Call-in but that is not listed by the Agency in Item 4. You must bring any such
apparent omission to the Agency's attention within the period required for submission
of this response form.
Item 5. ON BOTH FORMS: Check this item for each product registration you wish to
cancel voluntarily. If a registration number is listed for a product for which you
previously requested voluntary cancellation, indicate in Item 5 the date of that
request. Since this Data Call-In requires both generic and product specific data, you
must complete item 5 on both Data Call-In response forms. You do not need to
complete any item on the Requirements Status and Registrant's Response Forms.
Item 6a. ON THE GENERIC DATA FORM: Check this Item if the Data Call-In is for
generic data as indicated in Item 3 and you are eligible for a Generic Data
Exemption for the chemical listed in Item 2 and used in the subject product. By
electing this exemption, you agree to the terms and conditions of a Generic Data
Exemption as explained in the Data Call-In Notice.
If you are eligible for or claim a Generic Data Exemption, enter the EPA registration
Number of each registered source of that active ingredient that you use in your product.
Typically, if you purchase an EPA-registered product from one or more other producers
(who, with respect to the incorporated product, are in compliance with this and any
other outstanding Data Call-In Notice), and incorporate that product into all your
products, you may complete this item for all products listed on this form. If, however,
you produce the active ingredient yourself, or use any unregistered product (regardless
of the fact that some of your sources are registered), you may not claim a Generic Data
Exemption and you may not select this item.
224
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
Generic and Product Specific Data Call-in
Item 6b. ON THE GENERIC DATA FORM: Check this Item if the Data Call-In is for
generic data as indicated in Item 3 and if you are agreeing to satisfy the generic
data requirements of this Data Call-in. Attach the Requirements Status and
Registrant's Response Form that indicates how you will satisfy those
requirements.
NOTE: Item 6a and 6b are not applicable for Product Specific Data.
Item 7a. ON THE PRODUCT SPECD7IC DATA FORM: For each manufacturing use
product (MUP) for which you wish to maintain registration, you must agree to
satisfy the data requirements by responding "yes."
Item 7b. For each end use product (EUP) for which you wish to maintain registration, you
must agree to satisfy the data requirements by responding "yes."
FOR BOTH MUP and EUP products
You should also respond "yes" to this item (7a for MUP's and 7b for EUP's) if your
product is identical to another product and you qualify for a data exemption. You must
provide the EPA registration numbers of your source(s); do not complete the
Requirements Status and Registrant's Response form. Examples of such products
include repackaged products and Special Local Needs (Section 24c) products which are
identical to federally registered products.
If you are requesting a data waiver, answer "yes" here; in addition, on the
"Requirements Status and Registrant's Response" form under Item 9, you must respond
with option 7 (Waiver Request) for each study for which you are requesting a waiver.
NOTE: Item 7a and 7b are not applicable for Generic Data.
225
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
Generic and Product Specific Data Call-In
Item 8. ON BOTH FORMS: This certification statement must be signed by an authorized
representative of your company and the person signing must include his/her title.
Additional pages used in your response must be initialled and dated in the space
provided for the certification.
Item 9. ON BOTH FORMS: Enter the date of signature.
Item 10. ON BOTH FORMS: Enter the name of the person EPA should contact with
questions regarding your response.
Item 11. ON BOTH FORMS: Enter the phone number of your company contact.
Note: You may provide additional information that does not fit on this form in a signed letter that accompanies your response. For example, you may
wish to report that your product has already been transferred to another company or that you have already voluntarily cancelled this product. For
these cases, please supply all relevant details so that EPA can ensure that its records are correct
226
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Instructions For Completing The "Requirements Status and Registrant's Response
Forms" For The Generic and Product Specific Data Call-in
INTRODUCTION
These instructions apply to the Generic and Product Specific "Requirements Status and
Registrant's Response Forms" and are to be used by registrants to respond to generic and
product specific Data Call-in's as part of EPA's reregistration program under the Federal
Insecticide, Fungicide, and Rodenticide Act. If you are an end-use product registrant only
and have been sent this DCI letter as part of a RED document you have been sent just the
product specific "Requirements Status and Registrant's Response Forms." Only registrants
responsible for generic data have been sent the generic data response forms. The type of
Data Call-in (generic or product specific) is indicated in item number 3 ("Date and
Type of DCI") on each form.
Although the form is the same for both product specific and generic data, instructions for
completing the forms differ slightly. Specifically, options for satisfying product specific data
requirements do not include (1) deletion of uses or (2) request for a low volume/minor use
waiver. Please read these instructions carefully before filling out the forms.
EPA has developed these forms individually for each registrant, and has preprinted these
forms to include certain information unique to this chemical. DO NOT use these forms for
any other active ingredient.
Items 1 through 8 have been preprinted on the form. Item 9 must be completed by the
registrant as appropriate. Items 10 through 13 must be completed by the registrant before
submitting a response to the Agency.
The public reporting burden for this collection of information is estimated to average 30
minutes per response, including time for reviewing instructions, searching existing data
sources, gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding the burden estimate or any other aspect
of this collection of information, including suggestions for reducing this burden, to Chief,
Information Policy Branch, Mail Code 2136, U.S. Environmental Protection Agency, 401 M
St., S.W., Washington, D.C. 20460; and to the Office of Management and Budget, Paperwork
Reduction Project 2070-0107, Washington, D.C. 20503.
228
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS"
Generic and Product Specific Data Call-In
Item 1. ON BOTH FORMS: This item identifies your company name, number and address.
Item 2. ON THE GENERIC DATA FORM: This item identifies the case number, case
name, EPA chemical number and chemical name.
ON THE PRODUCT SPECIFIC DATA FORM: This item identifies the case
number, case name, and the EPA Registration Number of the product for which the
Agency is requesting product specific data.
ItemS. ON THE GENERIC DATA FORM: This item identifies the type of Data Call-In.
The date of issuance is date stamped.
ON THE PRODUCT SPECIFIC DATA FORM: This item identifies the type of Data
Call-in. The date of issuance is also date stamped. Note the unique identifier number
(ID#) assigned by the Agency. This ID number must be used in the transmittal
document for any data submissions in response to this Data Call-In Notice.
Item 4. ON BOTH FORMS: This item identifies the guideline reference number of studies
required. These guidelines, in addition to the requirements specified in the Data
Call-in Notice, govern the conduct of the required studies. Note that series 61 and 62
in product chemistry are now listed under 40 CFR 158.155 through 158.180, Subpart
c.
Item 5. ON BOTH FORMS: This item identifies the study title associated with the
guideline reference number and whether protocols and 1,2, or 3-year progress
reports are required to be submitted in connection with the study. As noted in
Section III of the Data Call-in Notice, 90-day progress reports are required for all
studies.
If an asterisk appears in Item 5, EPA has attached information relevant to this guideline
reference number to the Requirements Status and Registrant's Response Form.
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INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORMS"
Generic and Product Specific Data Call-In
Item 6. ON BOTH FORMS: this item identifies the code associated with the use pattern of
the pesticide. In the case of efficacy data (product specific
requirement), the required study only pertains to products which have the use sites
and/or pests indicated. A brief description of each code follows:
A Terrestrial food
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic-non-food residential
H Greenhouse food
I Greenhouse non-food crop
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
O Indoor residential
Item 7. ON BOTH FORMS: This item identifies the code assigned to the substance that
must be used for testing. A brief description of each code follows:
EUP End-Use Product
MP Manufacturing-Use Product
MP/TGAI Manufacturing-Use Product and Technical Grade Active Ingredient
PAI Pure Active Ingredient
PAI/M Pure Active Ingredient and Metabolites
PAI/PAIRA Pure Active Indredient or Pute Active Ingredient Radiolabelled
PAIRA Pure Active Ingredient Radiolabelled
PAIRA/M Pure Active Ingredient Radiolabelled and Metabolites
PAIRA/PM Pure Active Ingredient Radiolabelled and Plant Metabolites
TEP Typical End-Use Product
TEP % Typical End-Use Product, Percent Active Ingredient Specified
TEP/MET Typical End-Use Product and Metabolites
TEP/PAI/M Typical End-Use Product or Pure Active Ingredient and Metabolites
TGAI Technical Grade Active Ingredient
TGAI/PAI Technical Grade Active Ingredient or Pure Active Ingredient
230
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TGAI/PAIRA Technical Grade Active Ingredient or Pure Active Ingredient
Radiolabelled
TGAI/TEP Technical Grade Active Ingredient or Typical End-Use Product
MET Metabolites
IMP Impurities
DEGR Degradates
* See: guideline comment
Item 8. This item completed by the Agency identifies the time frame allowed for submission
of the study or protocol identified in item 5.
ON THE GENERIC DATA FORM: The time frame runs from the date of your
receipt of the Data Call-In notice.
ON THE PRODUCT SPECIFIC DATA FORM: The due date for submission of
product specific studies begins from the date stamped on the letter transmitting the
Reregistration Eligibility Decision document, and not from the date of receipt.
However, your response to the Data Call-In itself is due 90 days from the date of
receipt
Item 9. ON BOTH FORMS: Enter the appropriate Response Code or Codes to show how
you intend to comply with each data requirement. Brief descriptions of each code
follow. The Data Call-In Notice contains a fuller description of each of these options.
Option 1. ON BOTH FORMS: rDeveloping Data) I will conduct a new study and
submit it within the time frames specified in item 8 above. By indicating that
I have chosen this option, I certify that I will comply with all the
requirements pertaining to the conditions for submittal of this study as
outlined in the Data Call-In Notice and that I will provide the protocols and
progress reports required in item 5 above.
Option 2. ON BOTH FORMS: fAgreement to Cost Share1) I have entered into an
agreement with one or more registrants to develop data jointly. By indicating
that I have chosen this option, I certify that I will comply with all the
requirements pertaining to sharing in the cost of developing data as outlined
in the Data Call-in Notice.
However, for Product Specific Data, I understand that this option is available for
acute toxicity or certain efficacy data ONLY if the Agency indicates in an
attachment to this notice that my product is similar enough to another product to
qualify for this option. I certify that another party in the agreement is committing to
submit or provide the required data; if the required study is not submitted on time,
my product may be subject to suspension.
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Option 3. ON BOTH FORMS: (Offer to Cost Shared I have made an offer to enter
into an agreement with one or more registrants to develop data jointly. I am
also submitting a completed "Certification of offer to Cost Share in the
Development of Data" form. I am submitting evidence that I have made an
offer to another registrant (who has an obligation to submit data) to share in
the cost of that data. I am including a copy of my offer and proof of the
other registrant's receipt of that offer. I am identifying the party which is
committing to submit or provide the required data; if the required study is
not submitted on time, my product may be subject to suspension. I
understand that other terms under Option 3 in the Data Call-in Notice apply
as well.
However, for Product Specific Data, I understand that this option is available
only for acute toxicity or certain efficacy data and only if the Agency indicates in an
attachment to this Data Call-In Notice that my product is similar enough to another
product to qualify for this option.
Option 4. ON BOTH FORMS: (Submitting Existing Data^ I will submit an existing
study by the specified due date that has never before been submitted to EPA.
By indicating that I have chosen this option, I certify that this study meets all
the requirements pertaining to the conditions for submittal of existing data
outlined in the Data Call-In Notice and I have attached the needed
supporting information along with this response.
Options. ON BOTH FORMS: (Upgrading a Study-> I will submit by the specified
due date, or will cite data to upgrade a study that EPA has classified as
partially acceptable and potentially upgradeable. By indicating that I have
chosen this option, I certify that I have met all the requirements pertaining to
the conditions for submitting or citing existing data to upgrade a study
described in the Data Call-in Notice. I am indicating on attached
correspondence the Master Record Identification Number (MRID) that EPA
has assigned to the data that I am citing as well as the MRID of the study I
am attempting to upgrade.
Option 6. ON BOTH FORMS: (Citing a Studvt I am citing an existing study that
has been previously classified by EPA as acceptable, core, core minimum,
or a study that has not yet been reviewed by the Agency. If reviewed, I am
providing the Agency's classification of the study.
However, for Product Specific Data, I am citing another registrant's study. I
understand that this option is available ONLY for acute toxicity or certain efficacy
data and ONLY if the cited study was conducted on my product, an identical product
or a product which the Agency has "grouped" with one or more other products for
purposes of depending on the same data. I may also choose this option if I am citing
my own data. In either case, I will provide the MRID or Accession number (s). If I
232
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cite another registrant's data, I will submit a completed "Certification With Respect
To Data Compensation Requirements" form.
FOR THE GENERIC DATA FORM ONLY; The following three options (Numbers
7,8, and 9) are responses that apply only to the "Requirements Status and
Registrant's Response Form" for generic data.
Option 7. (Deleting Uses) I am attaching an application for amendment to my
registration deleting the uses for which the data are required.
Option 8. (Low Volume/Minor Use Waiver Request) I have read the statements
concerning low volume-minor use data waivers in the Data Call-In Notice
and I request a low-volume minor use waiver of the data requirement. I am
attaching a detailed justification to support this waiver request including,
among other things, all information required to support the request. I
understand that, unless modified by the Agency in writing, the data
requirement as stated in the Notice governs.
Option 9. (Request for Waiver of Data) I have read the statements concerning data
waivers other than lowvolume minor-use data waivers in the Data Call-In
Notice and I request a waiver of the data requirement. I am attaching a
rationale explaining why I believe the data requirements do not apply. I am
also submitting a copy of my current labels. (You must also submit a copy
of your Confidential Statement of Formula if not already on file with EPA).
I understand that, unless modified by the Agency in writing, the data
requirement as stated in the Notice governs.
FOR PRODUCT SPECIFIC DATA; The following option (number 7) is a response
that applies to the "Requirements Status and Registrant's Response Form" for
product specific data.
Option 7. (Waiver Request) I request a waiver for this study because it is
inappropriate for my product. I am attaching a complete justification for this
request, including technical reasons, data and references to relevant EPA
regulations, .guidelines or policies. [Note: any supplemental data must be
submitted in the format required by P.R. Notice 86-5]. I understand that this
is my only opportunity to state the reasons or provide information in support
of my request. If the Agency approves my waiver request, I will not be
required to supply the data pursuant to Section 3(c) (2) (B) of FIFRA. If the
Agency denies my waiver request, I must choose a method of meeting the
data requirements of this Notice by the due date stated by this Notice. In this
case, I must, within 30 days-of my receipt of the Agency's written decision,
submit a revised "Requirements Status" form specifying the option chosen. I
also understand that the deadline for submission of data as specified by the
original Data Call-In notice will not change.
233
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Item 10.
Item 11.
Item 12.
ON BOTH FORMS: This item must be signed by an authorized representative of
your company. The person signing must include his/her title, and must initial and
date all other pages of this form.
ON BOTH FORMS: Enter the date of signature.
ON BOTH FORMS: Enter the name of the person EPA should contact with
questions regarding your response.
Item 13. ON BOTH FORMS: Enter the phone number of your company contact.
Yon may provide additional information that does not fit on this form in a signed letter that accompanies this your response. For example you
may wish to report that your product has already been transferred to another company or that you have already voluntarily cancelled this '
234
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EPA'S BATCHING OF PARAQUAT DICHLORIDE PRODUCTS FOR MEETING ACUTE
TOXICITY DATA REQUIREMENTS FOR REREGISTRATION
In an effort to reduce the time, resources and number of animals needed to fulfill the acute
toxicity data requirements for reregistration of products containing paraquat dichloride as the
active ingredient, the Agency has batched products which can be considered similar for
purposes of acute toxicity. Factors considered in the sorting process include each product's
active and inert ingredients (identity, percent composition and biological activity), type of
formulation (e.g., emulsifiable concentrate, aerosol, wettable powder, granular, etc.), and
labeling (e.g., signal word, use classification, precautionary labeling, etc.). Note that the
Agency is not describing batched products as "substantially similar" since some products
within a batch may not be considered chemically similar or have identical use patterns.
Using available information, batching has been accomplished by the process described in
the preceding paragraph. Notwithstanding the batching process, the Agency reserves the
right to require, at any time, acute toxicity data for an individual product should the need
arise.
Registrants of products within a batch may choose to cooperatively generate, submit or cite
a single battery of six acute toxicological studies to represent all the products within that
batch. It is the registrants' option to participate in the process with all other registrants, only
some of the other registrants, or only their own products within a batch, or to generate all the
required acute toxicological studies for each of their own products. If a registrant chooses to
generate the data for a batch, he/she must use one of the products within the batch as the test
material. If a registrant chooses to rely upon previously submitted acute toxicity data, he/she
may do so provided that the data base is complete and valid by today's standards (see
acceptance criteria attached), the formulation tested is considered by EPA to be similar for
acute toxicity, and the formulation has not been significantly altered since submission and
acceptance of the acute toxicity data. Regardless of whether new data is generated or existing
data is referenced, registrants must clearly identify the test material by EPA Registration
Number. If more than one confidential statement of formula (CSF) exists for a product, the
registrant must indicate the formulation actually tested by identifying the corresponding CSF.
In deciding how to meet the product specific data requirements, registrants must follow the
directions given in the Data Call-In Notice and its attachments appended to the RED. The DCI
Notice contains two response forms which are to be completed and submitted to the Agency
within 90 days of receipt. The first form, "Data Call-In Response," asks whether the
registrant will meet the data requirements for each product. The second form, "Requirements
Status and Registrant's Response," lists the product specific data required for each product,
including the standard six acute toxicity tests. A registrant who wishes to participate in a
batch must decide whether he/she will provide the data or depend on someone else to do so.
If a registrant supplies the data to support a batch of products, he/she must select one of the
following options: Developing Data (Option 1), Submitting an Existing Study (Option 4),
Upgrading an Existing Study (Option 5) or Citing an Existing Study (Option 6). If a registrant
235
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depends on another's data, he/she must choose among: Cost Sharing (Option 2), Offers to
Cost Share (Option 3) or Citing an Existing Study (Option 6). If a registrant does not want to
participate in a batch, the choices are Options 1, 4, 5 or 6. However, a registrant should know
that choosing not to participate in a batch does not preclude other registrants in the batch from
citing his/her studies and offering to cost share (Option 3) those studies.
Eight products were found which contain paraquat dichloride as an active ingredient. In
addition, a number of Special Local Need (SLN) registrations based on these products were
found. The products have been placed into three batches and a "no batch" category in
accordance with the active and inert ingredients, type of formulation and current labeling.
Table 1 identifies the batched products. Table 2 lists the products which have been placed in
the "no batch" category.
Table 1
Batch
1
2
EPA Reg. No.
10182-115
10182-362
10182-372
NM95000300
OK95000400
TX95001000
48273-6
10182-111
NC82001000
NM94000300
OK94000400
SC82001100
TX81003202
TX93001400
TX94001100
TX96000500
10182-280
% Active Ingredient
43.5
43.5
43.5
43.5
43.5
43.5
43.5
30.3
29.1
30.3
30.3
29.1
29.1
29.1
30.3
30.3
37.0
Formulation Type
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
236
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Batch
EPA Reg. No.
AL94000500
AR95000200
CA91002100
CA9 1002200
CA9 1002300
CA9 1002400
CA91003100
CA9 1003600
CA92000600
CT90000100
CT9 1000400
DE94000200
DE96000200
FL90000900
FL9 1000300
FL91000600
FL96000900
GA94000600
GA95000800
HI9 1000 100
HI91001000
HI92000800
ID92001000
ID92001100
ID93000600
ID95000800
% Active Ingredient
37.05
37.0
37.05
37.05
37.05
37.05
37.05
37.05
37.05
37.05
37.05
37.0
37.0
37.05
37.05
37.05
37.0
37.05
37.0
37.05
37.05
37.05
37.05
37.05
37.0
37.0
Formulation Type I
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
237
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Batch
EPA Reg. No.
KY95000100
LA94000700
LA95000300
MD95000100 '
ME95000700
MI9 1000900
MN90000400
MN94000600
MO95000300
MS95000500
MT94000500
NC95000300
NC95000600
NH90000100
NH92000100
NJ90000500
NC9 1000200
NV91000300
NV93000500
NV93000501
OH90000600
OH91000100
OR91002300
OR93000900
OR93001900
PA90000100
% Active Ingredient
37.0
37.0
37.0
37.0
37.0
37.05
37.05
37.05
37.0
37.0
37.05
37.0
37.0
37.05
37.05
37.05
37.05
37.05
37.05
37.05
37.0
37.05
37.05
37.05
37.05
37.05
Formulation Type
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquit
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
238
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Batch
3
EPA Reg. No.
PA96000400
SC95000700
SD94000500
TN94000300
TN94000800
TN95000200
TX90000900
VA93000600
VA94001200
VA96000500
WA9 1004400
WA9 1004500
WA9 1004800
WA9 1004900
WA93001400
WA94003700
WA95000700
WI90000400
WY95000200
10182-103
AR95000900
LA95001500
MS95001400
OH88000200
PA87000200
TN94000700
% Active Ingredient
37.0
37.0
37.0
37.05
37.0
37.0
37.0
37.05
37.0
37.0
37.05
37.0
37.05
37.05
37.05
37.05
37.0
37.05
37.0
23.2
23.2
23.2
23.2
23.2
20.4
23.2
Formulation Type
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
239
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The following table lists a product that was considered not to be similar and was not placed
in any batch. The registrant of this product is responsible for meeting the acute toxicity data
requirements separately.
Table 2 (No Batch}
EPA Reg. No.
10182-120
% Active Ingredient
29.42 paraquat dichloride
10.66 diuron
Formulation
Type
Liquid
Products in Batch 1 may be supported by the data cited in the RED on the 45.6% technical
concentrate. Data on crystalline paraquat dichloride may be bridged to support Batch I.
Products in Batch 2 and Batch 3 may also bridge data from Batch 1 or from the RED for
support.
240
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Instructions for Completing the Confidential Statement of Formula
The Confidential Statement of Formula (CSF) Form 8570-4 must be used. Two legible,
signed copies of the form are required. Following are basic instructions:
a. All the blocks on the form must be filled in and answered completely.
b. If any block is not applicable, mark it N/A.
c. The CSF must be signed, dated and the telephone number of the responsible party
must be provided.
d. All applicable information which is on the product specific data submission must also
be reported on the CSF.
e. All weights reported under item 7 must be in pounds per gallon for liquids and
pounds per cubic feet for solids.
f.
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Flashpoint must be in degrees Fahrenheit and flame extension in inches.
For all active ingredients, the EPA Registration Numbers for the currently registered
source products must be reported under column 12.
h. The Chemical Abstracts Service (CAS) Numbers for all actives and inerts and all
common names for the trade names must be reported.
i. For the active ingredients, the percent purity of the source products must be reported
under column 10 and must be exactly the same as on the source product's label.
j. All the weights in columns 13.a. and 13.b. must be in pounds, kilograms, or grams.
In no case will volumes be accepted. Do not mix English and metric system units
(i.e., pounds and kilograms).
All the items under column 13.b. must total 100 percent.
All items under columns 14.a. and 14.b. for the active ingredients must represent
pure active form.
m. The upper and lower certified limits for ail active and inert ingredients must follow
the 40 CFR 158.175 instructions. An explanation must be provided if the proposed
limits are different than standard certified limits.
n. When new CSFs are submitted and approved, all previously submitted CSFs become
obsolete for that specific formulation.
243
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ง ฃฑ \ United States Environmental Protection Agency
1 ^W^ 1 Washington, D.C. 20460
V^'^y Certification of Offer to Cost
^PRCrtt Share in the Development of Data
Form Approved
OMB No. 2070-01 06,
2070-0057
Approval Expires
3-31-99
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including
time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and
completing and reviewing the collection of information. Send comments regarding the burden estimate or any other
aspect of this collection of information, including suggestions for reducing this burden to, Chief Information Policy
Branch, PM-233, U.S. Environmental Protection Agency, 401 M St., S.W., Washington, DC 20460; and to the Office of
Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Please fill in blanks below:
Company Name
Product Name
Company Number
EPA Reg. No.
I Certify that:
My company is willing to develop and submit the data required by EPA under the authority of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA), if necessary. However my company would prefer to
enter into an agreement with, one or more registrants to develop jointly or share in the cost of developing
data.
My firm has offered in writing to enter into such an agreement That offer was irrevocable and included an
an offer to be bound by arbitration decision under section 3(c)(2)(B)(iii) of FIFRA if final agreement on all
terms could not be reached otherwise. This offer was made to the following firms on the following date(s):
Name of Firm(s)
Certification:
Date of Offer
1 certify that 1 am duly authorized to represent the company named above, and that the statements that 1 have made on
this form and all attachments therein are true, accurate, and complete. 1 acknowledge that any knowingly false or
misleading statement may be punishable by fine or imprisonment or both under applicable law.
Signature of Company's Authorized Representative
Date
Name and Title (Please Type or Print)
EPA Form 8570-32 (5/91) Replaces EPA form 8580 which is obselete
-------
-------
United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
Form Approved
OMB No. 2070-0107,
2070-0057
Approval Expires
3-31-99
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including time for
reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding the burden estimate or any other aspect of this collection of information,
including suggestions for reducing this burden to, Chief Information Policy Branch, PM-233, U.S. Environmental Protection
Agency, 401 M St., S.W., Washington, DC 20460; and to the Office of Management and Budget, Paperwork Reduction Project
(2070-0106), Washington, DC 20503.
Please fill in blanks below.
Company Name
Product Name
Company Number
EPA Reg. No.
I Certify that:
1. For each study cited in support of registration or reregistratiion under the Federal Insecticide, Fungicide and Rodenticide Act
(FIFRA) that is an exclusive use study, I am the original data submitter, or I have obtained the written permission of the original
data submitter to cite that study.
2. That for each study cited in support of registration or reregistration under FIFRA that is NOT an exclusive use study, I am the
original data submitter, or I have obtained the written permission of the original data submitter, or I have notified in writing the
company(ies) that submitted data I have cited and have offered to: (a) Pay compensation for those data in accordance with sections
3(C)("')(F) and 3(c)(2)(D) of FIFRA; and (b) Commence negotiation to determine which data are subject to the compensation
requirement of FIFRA and the amount of compensation due, if any. The companies I have notified are. (check one)
[ ] The companies who have submitted the studies listed on the back of this form or attached sheets, or indicated on the attached
"Requirements Status and Registrants' Response Form,"
3. That I have previously complied with section 3(c)(1)(F) of FIFRA for the studies I have cited in support of registration or
reregistration under FIFRA.
Signature
Date
Name and Title (Please Type or Print)
GENERAL OFFER TO PAY: I hereby offer and agree to pay compensation to other persons, with regard to the registration or
reregistration of my products, to the extent required by FIFRA section 3(c)(1)(F) and 3(c)(2)(D).
Signature
Date
Name and Title (Please Type or Print)
bPA horm 8570-31 (4-96)
249
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The following is a list of available documents for Paraquat Bichloride that my further assist
you in responding to this Reregistration Eligibility Decision document. These documents may
be obtained by the following methods:
Electronic
File format:
2.
Portable Document Format (.PDF) Requires Adobeฎ Acrobat or compatible
reader. Electronic copies can be downloaded from the Pesticide Special Review
and Reregistration Information System at 703-308-7224. They also are available
on the Internet on EPA's gopher server, GOPHER.EPA.GOV, or using ftp on
FTP.EPA.GOV, or using WWW (World Wide Web) on WWW.EPA.GOV., or
contact Venus Eagle at (703)-308-8045.
Appendix A.
PR Notice 86-5.
3. PR Notice 91-2 (pertains to the Label Ingredient Statement).
4. A full copy of this RED document.
5. A copy of the fact sheet for Paraquat Dichloride.
The following documents are part of the Administrative Record for Paraquat Dichloride and
may included in the EPA's Office of Pesticide Programs Public Docket. Copies of these
documents are not available electronically, but may be obtained by contacting the person listed
on the Chemical Status Sheet.
1. Health and Environmental Effects Science Chapters.
2. Detailed Label Usage Information System (LUIS) Report.
The following Agency reference documents are not available electronically, but may be
obtained by contacting the person listed on the Chemical Status Sheet of this RED document.
1. The Label Review Manual.
2. EPA Acceptance Criteria
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