United States OHioe of Pesticides and Toxic Subsumes*
Environmental Protection Office of Pesticide Programs (TS-768C)
Agency Washington. DC 20460
c/EPA Pesticide
Fact Sheet
Name of Chemical: EPN
Reason for Issuance:
_ . . Issuance of Guidance Document
Date Issued: APR 3 0 1967
Fact Sheet Number: 127
1. DESCRIPTION OF CHEMICAL
Generic Name: 0-ethyl O-p-nitrcpheryl pherylphosphonothioate
Cannon Nane: EPN
Trade and None
Other
Names
EPA Shaughnessy Code: 041801
Chemical Abstracts Service (CAS) Number: 2104-64-5
Year of Initial Registration: 1949
Pesticide Type: Insecticide
Chemical Family: Organcphosphate
U.S. and Foreign Producers: Nissan Chemical Wbrks, Ltd. of Japan
There are no U.S. producers and there
are no U.S. registrations for technical
EPN. There were 32 end use EPN products
registered in the U.S. as of April 29, 1987.
2. USE PATTERNS AND FORMULATIONS
Application Sites: Cotton, soybeans, field corn, pecans,almonds, apples,
apricots, beans (green beans, lima beans, navy beans
red kidney beans, snap beans), black-eyed peas,
cherries (sweet and sour), citrus (citron, grapefruit,
lemons, limes, oranges, tangelos, tangerines), corn
(sweet), cowpeas, grapes, kunquats, nectarines, oliuesr
peaches, pears, pecans, plums, prunes, sugar beets,
tomatoes, walnuts, and earthworm farms.
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P ypes and t oda of Application: Foliar broadcast usir aerial or ground
uiptent.
Application Pates: Recannended application rates ranga fran 0.125 to 5.0
pDunds of active in raiient per acre.
1 ’pes of Fbrinulations: Emulsifiable concentrates; granular;
ettab1e pwder.
3. SCI JCE FINDIN(
Sunnary Science Stat nent
E is a non-hala enated, arcrnatic, plcsp)oncthioate or ancphospIorus
canpound with hi i aaite toxicity. A single oral dcee of the d nica1
has been sttwn to prcxlice o ancptosphate type delayed nairotoxicity in
the dc iestic hen. EPN has been sh to be non—teratogenic. Based on
all nut enicity tests rerie ed, EPN is considered to be non-rTut enjc
although EPN tethnical as ‘eak1y nuta nic in a sirqle replicate of one
of the tests utilized. I ta gaps ecist for thronic feeiirq, onccqenicity,
ard re roduction. EPN is highly toxic to aquatic or nisns arxi birds.
Tolerances haie been established for a rurnber of ra’i & riailtwal
canntxiities, howe er aiditional data are r uired to support nany of
then. The theoretical nuximum residue contribition (D4RC) for EPN is
0.9859 mg/kg/day. A pro.risional acc table daily int ce (PADI) of
0.00001 mg/kg/day has been caloilated for EPN based on the nost sensitive
study for delayed ne othxicity, a 90—day oral dcsing study in the hen with
a NOEL of 0.01 n jkg/day for irreiersible hist at1ol ica1 thanes in the
spinal cord. This effect has been identified as the n t sensiti e indicator
of EPW toxicity. The maximt.nn permissible intŕce (MPI) for EPN is calo.ilated
as 0.0006 mg/day for a 60 kg person. Based on these figures ard actual
residte data for 5 rerresentati e crqis, the IMRC oca.ipies 120% of the
PADI (usiri the percent of the crcp treated in the calo.ilation).
Applicators, mixei/loaiers ard field workers (makirg early reentry into
treated areas) are inur ily aaitely expcsed to EPN di. ing their ort
act ivi ties. Based on wera e cposixe values fran s ra ate pesticide
studies, the Agency calculated the daily nargin of safety for applicators
to be 0.05 for cotton, 0.01 for a ybeans, ard 1.4 for field corn. r ins
of safety for field or) rs, based on dislodgeable residua dissipation data
for EPN aid no Urotective c1othir , tere calciilated to be 30 at 7 days after
application to cotton; 30 at 2 days after application to soybeans, corn, and
pecans; ard 30 at 35 days after application to citrus. Certain uses of EPN
aleD ha e sufficient exp . e to pcse a potential ha rd to certain endan red
arK1/or threatened species of rnamnal.s, birde, aquatic or ania , crustaceans,
r tiles ard insects. EPN is sli itly persistent; howe r, insufficient data
are ia ilable for the Agency to fully assess the ervi rorme ntal fate aid
transport of the canpound.
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chemical Characteristics of the Technical Material
Physical State: Oily liquid (tedinical); c stalline rEwder (pure).
Color: Peddish—yell (tedinical); li t— ellc , (pure).
Odor: Arcm3 tic odor.
Moleoilar weight arri formula: 323.3 — C 14 Hj 4 t E jP 5 .
Meltiri Point: 34.5°C.
Varx:)r Pressure: 0.03 mnt!g at 100°C (tedmical).
Specific Gravity: 1.27 at 20°C.
So]iibility in variais zlvents: Miscible with berzerie, toluene
xylene, acetone, isc cpyl a1cot l,
an nethanol; slightly ]j.ible in
in ater.
Toxicoloqy Characteristics
Acute Oral: High acute oral toxicity to nemrtals with toxicity values
of ap rc dmately 52.8 mg/kg/body eiqht in nale rats an
13.2 maJkg/body eight in f ale rats.
Toxicity Cat ry I.
Acute De mal: 354 mg/kg/body iqht in iiale rabbits ard
500 rnaJkg/body ight in fanale rabbits.
Toxicity Category II.
Primary Deiinal Irritation: Ičd nica1 EPN does nct çrodice dexxnal irritation.
Toxicity Category IV.
Primary Eye Irritation: Ted -inical N does nct gzodice e 2 ’e irritation
Toxicity Category IV
Skin Ser iti tion: t ta gap.
Acute Inhalation: Extrenely aaite inhalation toxicity with values f
0.076 mcJL in nale rats ard 0.024 mg/L in fenale rats
Toxicity Category I
Major roites ± cposure: mal cposure, with sine inhalation
expcsure, to applicators.
1 1ayed ne. rotoxicity: N causes or ancp sphate-type delayed nairotoxic
effects in test aninals. Histcpat logica1 cthan s
re seen at 0.1 majkg/day; clinical effects (at cia)
were seen at 2.5 ma/kg/day.
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coganicity: Data gap.
Chronic Feedirr Data gap.
Metabolian: Partial data gap. Data resenUy available to the Agancy
show the e dstence Cf se eral pcssible rtetabolites, howe r,
these iretabolites re not identified. FUrther wo must be
perforned to identify the netabolites of FPN.
Teratogenicity: N is not teratogenic.
Re oduct ion: Data Gap.
tita enicity: EPN is not corsidered to be mut enic based on all cf the
nutagenicity tests revie d, alth gh EPN technical s eakly
nuit enic in a single r licate Cf one cf the tests utilized.
Physiological and Biochemical Characteristics
Methanisn cf Pesticidal Action: Cholinesterase inhibition following
contact with, or ingestion of, EPN
treated s f aces.
Metaboli n and Persistence in Plants and Aninels: A ilable data indicate
that EPN is Si igh tly persistent, hcweve r,
these data are irsufficient to fully assess
the ranspDrt Cf EPN. Altftlzgh the netabolisn
of N in plants is not adequately understood,
detailed characterization Cf residues in
wtole, lO— ’eek old cotton plants has re’ ealed
the pesence Cf EPN and b o netabolites,
0-ethyl pheny1phcEp cnic acid and phenyl—
pFosptonic acid. This stuiy also re.realed
that ‘ 4 C—residues of [ 1k] EPN are absorbed
into plant tissues following foliar apDlication.
Su1 nitted data pertaining to the rretabolisn Cf
N in anina]s indicate that EPN residues will
tranefer to tissues Cf pultty, but othei wise
are inad&iuate to show the nat e Cf thcse
residues in pultLy or other animals.
Envj ronrrental Characteristics
Available data are irsufficient to fully assess the ervironnental
fate and trarsprt of EPN and the çxtential expceixe Cf hunans and
nonta et ou anisns to EPN. Data gaps ist for nearly all plicable
studies. Howe r, a .eilable relimina infornetion indicate general
trer Cf EPN behavior in the ervirorment. N is slightly persistent
and degrades in aerobic sandy loam soil, with a half—life of 4 to 8 ed s.
Pheryl p osç*onic acid, 0-ethyl pheryl ptcspfcnic acid, and 0-ethyl
phcsptonothioic acid are expected to be the nain degradates under aerobic
corxlitiorE. Data airrently available are insufficient to characterize EPN’s
leaching çxtential for contamination of gronnd ter. Data to characterize
the ptential Cf EPN to contaninate groindwater are being required. Treated
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areas sP i1d not be re-entered for at least 7 days for corn or cotton crqs,
35 days for citrus, and 2 days for all other cr s, unless trotecthe clothing
is crn
Ecolc ical Characteristics
Avian aoite toxicity: LE ij values cf 7.09 to 27 mg/kq for n 1 lard
duck; 53.4 mg/kg for rirg—neded pheasants, and
5.25 mg/kg for cctixnix.
Avian dieta toxicity: 8—day Dietary LC 5 O values of 168 ppm in
mallard dick and 349 ppm in botwhite quail.
Fresh ater fish acite toxicity: 96—hour r.c 50 values ranged fran
80 /L for rainboQ trait to
190 t /L for bluegill.
N rine fish acite toxicity: 96—hour LC 5 O values ranged from
37 u /L for Spot to 140 u/L for
1eq)shead.
Fres water irvertebrate toxicity: 48-hour LC 50 values rarqed fran
0.32 i. /L for I phnia m na to
36.0 /L for Gar marus lacustris .
rine invertebrate toxicity: 96—hour LC 5 O values ranged fran
4.6 i. /L for Penaeus Stylirostris to
13.0 u /L for Mysid sis bahia.
TOLERANCE REASSESSMENT
Tolerances hate been established for residues cC EPN in a variety of ra
ricult x al cannodities (40 CFR 180.119). The Agency has evaluated the
residue and to cicolcx y data supprtirq these tolerances and has detemtined
that a full tolerance reassessnent for EPN cannot be nede at this tine
because of exterEive residue ctheni stry and toxicolcx y data geps. Because
of these exters he data gep s, no s iqii f icant n e i uses, inc ludi ng gr 0.1 p
tolerances, will be granted until the Agency has received data sufficient
to tlorcughly evaluate the dietary exp e to EPN. (The Agency has actual
residue data for five cr s: soybearE, drybearE, ta toes, corn and cotton.
Taking the percent of crcp treated into acca t, the Agency believes that
i t is unlikely that EPN residues on crq s wi 11 be esent at the tolerance
levels listed.
The çresent United States tolerances and Mexican tolerances are listed
bela ,. No Canadian tolerances or Codex MRLs have been established for EPN.
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Sunu ry of Present EPN Tolerances
Cce dity
Apples
Act iccts
Bears
Beets
Beet greers
Blackberries
Bcysert ,erries
C.berries
Citxus fruits
Car n
De ,berries
Grapes
Lettu e
Logenberries
Nectarirss
Oli s
Pea:*ies
Bears
Pine ples
Pluns (fresh pr .nes)
Quinces
Ras çlJerries
Rut aa S
Ritabages tcps
Spinath
Strawberries
Sugarbeet tcps
Tm toes
Turnips
Turnip greens
Yc irr berries
Alno ri
Ccttonseed
Pecans
lmts
Sc,ybears
r its
Tolerance (p n)
United States Mexico
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0 3.0
3.0 3.0
3.0
3.0 3.0
3.0 3.0
3.0 ——
3.0
3.0
3.0 3.0
3.0 3.0
3.0 3.0
3.0 ——
3.0
3.0
3.0
3.0 ——
3.0 3.0
3.0 3.0
3.0
3.0 3.0
3.0 ——
3.0
3.0
0.5
0.5 0.5
0.5
0.5
0.05 0.05
0.5
The data for EPN residues in or on bears (dried), cottonseed, ta a toes, a rEi
corn are adeiuate to supg)rt the respect he established tolerances. Howe’ er,
the Agency rauires that the tolerance for residues in or on corn be d arqed
to t o tolerances, eacth at 3 ppn, for residues in or on field corn grain and
s et corn (Ice rnels plus cob with husks renoved) ar that the tolerance for
residues in or on beans be thanged to three tolerances for residues in or on
dried bears at 3 ppi , ard lirna ard sn bears for which a3ditional data are
r uired.
3.0
3.0
(sit not sugar
beet tcps)
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Data are nct edequate to su rt the established tolerance for residues in or
on airronds, apples, apricots, beans (snap and lina only), cherries, citrus,
grapes, lettce, nectarines, olives, peaches, pears, pecane, plurr , scybearis,
su r beets (witha.it tcps), and lruts.
There are air rently no re i stered use for the follc ii r crcps for which
tolerances are established: beets and beet greens, blackberries, bcysen—
berries, dewberries, 1 — nberries, pineapples, quinces, r as berries, rutabaga s,
spinach, strawberries, turnips and turnip greens, and yc*ingberries. The
Agency will re,de the air rently established tolerances for these ra
agricultural caniTodities, tnless the registrant s Amits usage rc xsals
and the required data to supprt the tolerance.
The Agency will also nove to revo} the tolerance for residues of EPN in or
on i:utabaga tcps since tutabaga tps are nc resently corsidered a ra.
agricultural ccmnt)ditity cf itaba s and no registered use of EPN on
utabagas exists,
The theoretical JTaximum residue contri ition ( IMRC) for EPN is 0.9859 mg/kg!
day. Apraiisional acceptable daily int ce (PADI) of 0.00001 mo/kg! day has
been calculated for EPN based on the rrc t sersiti .e study for delayed neuro-
toxicity, a 90—day oral dosing study in the hen with an LEL of 0.1 mg/kg/day
for hist attological evidence Cf toxicity in the spinal cord, a NOEL of 0.01
mg/kg/day ard a safety factor or tn certainty factor Cf 1000. HistcpatlDlcçical
changes in the spinal cord have been identified as the n t sersitive indicator
of EPN toxicity. The n ximum pe intl ss thle int e (MPI) for EPN is cal o.il a ted
as 0.0006 mg/day for a 60 kg irdividual. Based on these figures the IMRC is
equivalent to 164,000% Cf the P?DI. However, the Agency believes that this
figure is actually much lower. For five crqs for which the Aqenoj has actual
field residue data, the ‘IMRC oco.ipies 120% Cf the RADI, assuming the ap opriate
percent Cf crrp treated for each crcp.
4. Required Unique Labeling and Regulatory Position Sunuary
The Ageno/ is initiating a Special Revie i for all registered uses Cf EPN
based on the results Cf the delayed neurotoxicity studies, and the risks
to the pthlic fran corsuiption Cf food camrodities containing EPN residues
and risks to orkers involved with EPN application and working in fields
treated with EPN. The use 1 EPN neelror ecceeis the criteria for
edverse effects (40 CFR 154.7 (a)(2)).
The Agency greiioisly reiie ed EPN in the special reiiei ocess in
1979 when a N ice of Reb.ittable PresulTption Ageinst Registration
was issued (44 FR 54384) based upn studies sFo’iing that EPN caused
delayed neurotoxic effects In test anin 1s, and as aoitely toxic
to aguatic o1 iganisis. The Agency concluded’ that special re. ie i
with pWlication Cf its final nc*ice of determination in the
Federal Register on August 31, 1983 (48 FR 39494) anno.incing:
o the cancellation Cf the nEsquito larvicide use of EPN;
o the çvththition Cf the use Cf hui n flagers durirg
aerial application of N uiless the flajgers were
in totally enclosed vehicles;
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the re uirenent for standardized labeling state ents
for the use Cf gzotective c1 hing;
o the reluirenent for labeling statenents re rding
drift Cf EPN fran treated areas; and
o the re uirenent for labeling statenents rarnirq of
the h ard cI EPN application to crcps visited
by bees.
The e iais special rwi i of EPN relied primarily on the NOEL of
0.1 mg/kg/day for EPN-inijced depression cf plaai a and red blood
cell c*oinesterase levels in hunBrs as the NOEL for delayed
ne.irotoxicity. ( that basis, the Agency cala.ilated diet&y and
applicator risks pcsed by continued uses of N. The Agency
concluded at that tine that adequate ma rgi re Cf safety existed
for hunan dietaiy expcs e and for applicators with the cception
of flaggers.
Infoiinatjon received since that tine on veriois diolinesterase—jnhibiting
canpounda indicates an effect on blood c olinesterase is nct the rr t
sereitive indicator Cf toxicity for oz anq osphates. Ne infoimation on
recovel:y after a single large dcee of EPN in hens indicates that the spinal
histcpatFolcqica]. thanges are a itore sensitive indicator Cf toxicity and
that these d anges are irreversible. This finding has led the Agency to
conclude that the nost apçrcpriate NOEL to use for risk assessnent pirposes
and the n t sensitive indicator Cf xtential human toxicity for this
histcpatl-ological. effect is 0.01 mg/kg/day fran a 90-day stbdiornic
feeding stuc ’ in hens.
No significant nei uses, including gro.ip tolerances, will be granted
ix t ii the Agency has rece ived data sufficient to tPorcughly evaluate the
dietary expos e to EPN.
The Agency is continiing the restricted use classification Cf all liquid
fornulatiore and ary formulation greater than 4 % EPN. pplicat ion nust be
made by, or u der the direct supervision Cf, Certified Applicators. Direct
supervision for EPN oducts is defined as the Certified Applicator being
physically esent during ntxing, loaiing, equipient r air, and e uip ent
cleaning. Applicators nust eret.te that all per ns involved in these act ivities
under their direct supervision are infoLrned Cf the ecaitionaty statenents.
The Agency is requiring a label statenent concerning the histc atFological
changes in the spinal cord to be used in conjunction with the restricted use
statenent.
Endangered species labeling will be required at a later date for certain
use patterns of EPN. Specific labeling requirenents will be impcsed thr:u h
a Pesticide Regi strat ion (W) Not ice.
Preliminary evaluation Cf recently stbmitted toxicity and dissipation data
indicate that the 24—hair reentry interval established in 1974 for EPN
under 40 CFR 170.3 (b) (2) does nc ix ovide adequate x ect ion for field—
workers. Therefore, uttil the Agency receives aoite delayed neirctoxicity
data on t4iith to base the risk asses snent to determine the nxst effective
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reentry interval for EPN, the Agencj is requiring the following reentry
intervals: 7 days for corn ard cotton; 35 days for citrus; ard 2 days for
all other crcps.
rk safety rules, çzecautionaLy statenents, ard protective clothing
statenents for mixer/loa iers ard applicators are re uirei to be inc]uded
on the label of EPN çrod ts.
All EPN erd—use a tct labeling is re uirsi to contain wo safety rules,
pecautionary stater ents, and otecti’ e clothing statenents.
The Agency is r uiring pro ssing data for the bllo irq ra ariailtural
coTutod ties: sugar beets, soybeans, to ’iatoes, citrus, pr .nes, grapes,
apples, cot torn eed, corn, a rd olives.
The Agency is requiring the aidition cf the telep one nuirber cf the
National Pesticide Teleconminicatiors Netwo]J to all erd-use EPN prodicts.
Sthile data gaps are being filled, c zrently registered narufactiring use
prcthcts ard erxi use L cthcts containg EPN nay be sDld, distribited,
formulated, and used, s b ct to the terrts ard conditiorn specified
in the Registration Stardard for EPN. Pegistrants must rrcwide or
ee to de lgD aiditional data in order to naintain existing
regi stratiors.
5. Sunuary of Major Data Gaps
Tox icolo y
Acute delayed nairotoxicity - single dcse NOEL
t rmal sersiti tion
Chronic toxicity ( o species - rodent ard non-rodent)
Oncogenicity study (t o species — rat ard moise eferred)
Reprodact ive study
1 taboli sn
Env irorrnental Fate
Hydrolysis
Photod raiatlon, ‘ater
Photodegrathtinn, sil
Aerobic net ,olisn
Anaerobic netaboli sn
Leaching ard aisorptiorVdesorption
Soil dissipetion
Long—term soil dissipetion
Rotational cr (confined)
Rotational crq (field)
Fish accumulation
Drcplet size spectrum
Sp-ay drift field evaluation
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Ec1o ica1 Effects
Avian r rcx1iction stuiy
Fish early life—sta study
Aquatic irwertebrate life—cycle stady
A uatic mDnitorir or nesDcosm study
Residue Chanistry
Sthrac stability study
Plant n tabolisn stixly
Aninal netabolism study
Residue data for alnorth, apples, apricots, beans (snap ard lima), cherries,
citrus, grapes, lettice, nectarines, olives, peadies, pears, pecans, plums,
soybeans, si.qar beets (wittnit tcps), ard wairuts.
Resid .e data and usa propcsal for beets ard beet greens, blackberries,
bcysenberries, dewberries, lo nberries, pineapples, quinces, ras erries,
i utaba s, spinach, strawberries, t nips ard t -nip greens, and ycxir berries.
(tolarances for these it ns will be re,d(ed if residue data ard us e trcposal
are not subrrd.tted)
Proces si rg data for residues cf EPN in si.qa r beets, soybeans, tana toes, c i tru s,
pr nes, grapes, apples, cottonseed, corn, ard 01 i S.
Residue data ard tolerance grcposals for bean vines ard haj, stz ar beet tc s.
Special Processinq Studies to xovide:
Residue data for coded (micro avirg ard boilirq) s et corn.
Pes idt data on fresh un eshed tonatoes
A shin stuiy to prcvide residue data on lettace
7 • ca rrAcr PERSON AT EPA
Dennis Edwar
Actin Product t n er (12)
Insecticide-Rodenticide Brandi
Registration Division (TS—767C)
Office Pesticide Prcx ra! s
Environnental Pr ection A ncy
401 M Street, S. W.
% shington, D . C. 20460
Office location ard telepFone ruinber:
lbcin 202, Crystal Mall #2
1921 Jefferson Davis Highway
Arlington, VA 22202
(703) 557—2386
DISaAIMER: The information presented in this Chanical Infotination Fact
eet is for infornational purpcees only ard may not be used
to fulfill data re uirenents for pesticide registration aid
reregistration.
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