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Agency Wohington. DC 2O460
&EPA Pesticide
Fact Sheet
Name of Chemical: Acephate
Reason for Issuance: issuance of a Registration Standard
Date Issued: 10/37
Fact Sheet Number: 140
1. Description of Chemical
Generic Name: 0,S-dimethyl acetylphosphoramidothioate
Common Name: Acephate
Trade Name: Orthene
EPA Shaughnessy Code: 103301
Chemical Abstracts Service (CAS) Number: 30560-19-1
Year of Initial Registration: 1974
Pesticide Type: Insecticide
Chemical Family: Organophosphate
U.S. and Foreign Producers: Chevron Chemical Co. (U.S.A.)
2. Use Patterns and Formulations
Application Sites: Agricultural crops; ornamentals (field grown,
greenhouse, and home garden); lawns and turf; pasture and rangeland;
forestry; indoor homeowner use on houseplants; and commercial appli-
cator use in residential and commercial buildings including food
processing establishments.
Types and Methods of Application: Aerial; ground; direct injection
into tree trunks; dip treatment (ornamentals); soil incorporated; and
sprinklers.
Type of Formulations: Granular, pressurized liquid, soluble
concentrates (both liquids and solids), and cartridge.
3. Science Findings
Summary Science Statement: Acephate has a relatively low acute
toxicity to laboratory animals through the oral, dermal, and inha-
lation routes of exposure. Based on the available evidence, i.e.,
findings from the mouse oncogenicity study, and the mutagenicity
assays, the Agency has classified the chemical as a category C
carcinogen (a possible human carcinogen). The mouse oncogenicity
study indicated a statistically significant increase in the propor-
tion of liver adenomas/carcinomas and hyperplastic nodules occurred
only in the high dose (1000 ppm) females and only at the time of
terminal sacrifice. The EPA Guidelines for carcinogenic
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risk assessment (FR September 24, 1986) were followed for the evalu-
ation and the classification of the oncogenic effect of acephate.
Following the guidance set forth in the EPA guidelines, the mouse
oncogenic response was considered as “limited evidence.”
The available data are not sufficient to enable the Agency to
accurately assess the potential risk to humans from this oncogenic
effect resulting fran exposure to acephate. The data gaps include
residue reduction studies, exposure studies, usage data, a dermal
penetration study, a glove permeability study, and reentry data.
The available rat reproduction study showed reproductive effects at
50.0 ppn, the lowest dose tested. A new rat reproduction study is
needed to determine the no—observable—effect level (NOEL) for the6e
effects and to enable the Agency to assess the potential risk to
humans resulting from exposure to acephate.
Methylthioacetate (MTA) occurs as an impurity in the current
registered technical material. The available data suggest that the
MTA, despite its generally low acute toxicity, may pose a hazard to
the optic tract and pituitary gland in rabbits and other mammals at
low doses. Data were not provided to demonstrate a NOEL for lesions
at these target organs. Since visual impairment is inherently
difficult to diagnose in animals, it is possible that this effect
occurred in other studies but was not detected. In addition, a
mutagenic effect was seen in the mouse lyinphana assay in the activated
system. 1 Je to the insufficiency of the submitted data to explain
the toxic and mutagenic potential of MTA, the Agency requires that
additional studies be performed.
Methamidophos, the cholinesterase—inhibiting metabolite of acephate,
is also an insecticide in its own right, and as such, was assessed
under a separate Registration Standard issued for the chemical in
September 1982. Several of the data gaps identified in that standard
have been fulfilled. It is highly toxic by both the oral and dermal
routes (Toxicity Category I). Results of two oncogenicity studies
show that methamidophos was not oncogenic in rats at dose levels of
2,6,18 and 54 ppi nor in mice at dose levels of l,5,and 25 ppTi. The
available teratogenicity studies show that it is not teratogenic to
rats or rabbits. The chemical was negative for acute delayed
neurotoxicity in the submitted study on hens. The lowest effect
level (LEL) for cholinesterase inhibition activity was determined
to be 2 pçm (0.05 mg/kg/day) in both the 1—year dog study and the
2—year rat study.
Data gaps for methaniidophos include a rat reproduction study and
mutagenicity studies.
Chemical Characteristics
Physical State: Solid
Color: White
Odor: Strong, pungent, mercaptan-type
Boiling Point: N/A
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Melting Point: 82—89 °C (97% technical)
Flawriability: N/A
Solubility in Water: High solubility 65%)
Toxicology Characteristics:
ACEPHATE :
o cute Oral — Rat: 945 mg/kg (male); 866 mg/kg (female)
Toxicity Category III
o Pcute t rmal — Rabbit: > 10,000 mg/kg (male)
Toxic ity Ca tego y III
o Pc ute Inhalation — Rat: > 61.7 mg/kg (male and female)
Toxicity Category IV
o Pcute t layed t urotoxicity — Hen: gative at 785 mg/kg of
body ight
o use (Yicogenicity: Female mice fed 1000 p xn of technical
acephate (highest dose tested) had a statistically
significant higher ircider*e of hepabxellular cattin as
(15.8%) and hyperplastic nodules (19.7%) than did the
controls.
o Rat C cogenicity: Nt orcogenic to male and female rats
under the conditions of the sUx y; highest dose tested
s 700 ppn (35 mg/ kg).
o Rat throri ic Feed ing: LEL = 5 p n (0.25 mgi’ kg) based on the
inhibition of cholinesterase activity in pla&na, RBC,
and brain.
) D g Chronic Feeding: I .XJEL = 30 pixn (0.75 mg/kg) based on
the inhibition of pla na, RBC, and brain cholinesterase
activity. ? DEL = > 100 p xn (2.5 mg/kg) for systemic
toxicity.
o Rabbit ratogenicity: t fetotoxic or teratogenic at
10 mg/kg (highest dose tested).
o Rat ratogenicity: Nt teratogenic at 200 mg/kg (highest
dose tested).
o ttitageriic ity: The available stu ies irid icate that acephate
can indice gene mutations, D N A repair, and sister
chxxxnatid exchanges. Ho ver, in vivo st ies did r t
indicate that these effects and structural chranosa
aberrations are prockced at a detectable level in an
intact mam al ian system.
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o Rat Reprodution: Various reprod ctive eff ts (low
pregnarcy rate, high loss of total litters, high fetal
losses, decreased size and weight of total litters, arid
dereased n nber of live fetuses) were observed at the
lowest dose level tested, which was 50.0 ppn of tehnical
acephate (93% acephate).
ME’rHYLTH IC CEThTE ( MrA) :
o ?cute Dermal - Rabbit: 1720—2820 n f kg; Toxicity Category 11—111.
Clinical signs ircluded irreversible abserce,/di,ninution of
pupillary light reflex arid apparent blindness.
o k ute Inhalation — Rat: 3.47 mg/L; Toxicity Category III.
o Skin Irritation — Rabbit: 2.6 Primary Irritation Seore;
Toxicity Category III.
o Skin Sensitization — Guinea Pig: Nnsensitizing and
r nirritating; dose level tested was 0.3 ml (0.3 g).
o Eye Irritation — Rabbit: Toxicity Category III; dose level
tested was 0. 1 mL of 93. 5% MT .
o Mutajenic ity - Mouse Lymphana Assay: Mutajen ic to lymphana
cells in the activated system but not in the nonac tivated
system; levels tested were 1—10,000 uqjml (activated)
and 10—5000 ug/ml (r nactivated).
Physiological and B ixhemical Behavioral Characteristics :
Translcxation: The available plant metabolisn studies show
that acephate residues are readily absorbed by the roots
and trarisl ated throujbout the plant. wever, data show
that acephate does r t accunulate in carrt plants rotated
in acephate-treated soil or in fish, daphnia, or diatans.
Me hanisn of Pesticidal k tion: cephate is a contact arid
systemic insec tic ide. As an or9anophosphate, acephate
exerts its toxic action by inhibitir certain important
enzymes of the nervous system (cbolinesterase).
Metaboli&n arid Persisterce in Plants arid Animals: The netaboli n
of acephate in plants arid animals is adequately understood.
Available data s w that the residues in or on plants
resulting fran acephate use may be laz ely or wholly intact
acephate arid its netabolite, neth nidopbos. Available
animal metabolisn data show that most of the radiolabeled
material is rapidly eliminated fran the body arid that a
majority of the material is excreted in the urine.
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Methamidophos is not the major metabolite in ruminants.
About 80 pez:cent of the radiolabeled material in the urine
was ass’xiated with urchanged acephate arid less than 10
petcent with the metabol ite 0, S-d imethylphosphorothioate.
Most of the methamidophos formed is probably eliminated arid
exc re ted in the urine as 0, S—d irne thylphosphorthioate.
Environmental Characteristics :
We to its rapid leaching behavior, acephate has the ptential
for ground water contamination. Available data are insuf-
ficient t’) fully assess this potential. Pertinent data
(mobility, phot x ejradation , metabolian, arid dissipation) —
are being required under the Pcephate ReQ istration Standard
on an accelerated basis.
Available soil metabolisii studies show that acephate
dissipates rapidly with half—lives of < 3 and 6 days in
aerobic and anaerobic soils, respectively. The major meta-
bolite was CO 2 in both types of soil. The available leaching
data irclude a soil thin—layer chr iiiatography (TLC) study
arid a soil column study. Results of these studies indicate
that acephate is mobile in most soils but that aged acephate
residues (exc luci i rxj acepha te a rid its degrada te ne tham idophos)
are immobile in sandy loam soil. Apparently most of the
applied acephate arid the dejradate methamidophos degrade to
immobile ccxnpounds in 20 days.
Ecological Characteristics :
o Avian Oral Pcute Pxicity: 350 mg/kg (mallard) and 140 mg/kg
(pheasant)
o Avian Dietary Toxicity: > 5000 ppe (mallard) and 1280 p xn
(bobwhite)
o Fish Pcute Toxicity: > 1000 pp (rainb trout) arid > 1000 p n
(bluegill sunfish)
o Freshwater Invertebrate P ute Toxic i ty: > 1000 p n (thiror inus)
and > 100 (G ririarJs)
o Avian Repradu tion: JEL = > 5 p n but < 20 p xn for mallard arid
NCiEL = > 20 ppn but < 80 p xn for bobwhite.
o Honey Bee ute Toxicity: 1.2 ug/bee.
Based on these studies, acephate is mx1erately toxic to avian
species, practically nontoxic to freshwater fish arid freshwater
invertebrates, arid highly toxic to honey bees.
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However, acephate’s metabolite, methamidophos, has been shown to
be very toxic to birds. Therefore, additional testing (residue
monitoring studies) are being requested to complete a hazard
assessment for the multiple—application, high—use rate field
crops. Appropriate labeling for the protection of endangered
species determined to be in jeopardy from use of acephate on
forests, range and pastureland, soybeans, and cotton have been
developed by the Agency and were imposed under PR Notices 87—4
and 87—5.
Tolerance Assessment :
Refer to Attachment A for the list of currently established tolerances
for acephate as well as the tolerance changes to be initiated by the
Agency.
To achieve compatibility with the maximum residue levels of the
Codex Alimentarjus Commission, the following revisions in 40 CFR
180.108, 21 CFR 561.20, 40 CFR 180.315, 21 CFR 561 .277, and 21 CFR
193.10 are to be initiated by the Agency.
o 40 CFR 180.108 and 21 CFR 561.20
The acephate tolerances currently established under these
sections are to be expressed in terms of only acephate
se, with references to 40 CFR 180.315 and 21 CFR 561 .277
indicating that tolerance for the metabolite methamidophos
are also in effect.
o 40 CFR 180.315 and 21 CFR 561 .277
The methamidophos tolerances currently established under
these sections are to be divided into parts (a) and
(b) where (a) includes (1) tolerances reflecting uses of
methainidophos and (2) tolerances where both acephate and
methamidophos formulations are used on the same crop and
(b) includes tolerances reflecting uses of acephate formu-
lations alone, i.e., residues of methamidophos resulting
from the metabolism of acephate.
o 21 CFR 193.10
These food additive tolerances reflecting crack and crevice
treatment in food-handling facilities are to be expressed
in terms of only acephate se, i.e., based on the avail-
able data. No residues of the metabolite methamidophos are
expected to occur (< 0.001 ppn) in or on these foods.
Also, such a change in the residue definition would require deletion
of the paragraph (d)(8) of 40 CFR 180.3, which states that methamido—
phos residues may not exceed the higher of the two tolerances estab-
lished for the use of acephate or methainidophos as a pesticide.
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The tolerance for acephate residues in milk has been found likely
to be exceeded if maximum levels of spent mint hay or grass hay are
included in the dairy animal diet. Labeling restrictions prohibit-
ing the feeding of spent mint hay and grass hay to dairy animals
are being imposed under this Standard for the use of acephate on
pasture, rangeland, peppermint, and spearmint. If the registrant
elects to submit additional residue data to support a lower toler-
ance for grass and grass hay, or to support a longer pregrazing or
preharvest interval for dairy animals, the labeling restriction
for use on pasture and rangeland would be imposed as an interim
precautionary measure pending submittal and evaluation of these
data.
Available data are not sufficient to conduct a full tolerance
assessment. Data gaps exist for magnitude of residue studies,
residue storage stability studies, a dairy cattle feeding study, a
rat reproduction study, and a rat feeding study.
4. Summary of Requlatory Position Arid Required Unique Labeling
Registration of current registered uses of acephate is to be continued.
Additional data to allow the Agency to better define the dietary,
occupational, and dc nestic exposure risks frai’ the registered uses of
the chemical are being required. Once the Agency has evaluated these
data, it will determine whether the chemical should be placed in
Special Review or returned to the normal registration process.
Pending submittal and evaluation of these data, no additional
tolerances, including temporary tolerances, will be established for
acephate and no new uses will be registered, i.e., uses that would
result in an increase in the current exposure to humans or in new
exposure to humans.
As interim measures to reduce exposure pending submittal and
evaluation of the additional studies specified above, the following
restrictions are being imposed or, in the case of the last restriction
concerning danestic use, continued: A reentry interval of 24 hours
for fieldworkers; the use of protective clothing, including
chemical—resistant gloves, long—sleeved shirts and long—legged
trousers, shoes and socks by mixer/loaders, applicators, and early
reentry workers who may be exposed to treated plant surfaces within
24 hours of acephate application; dairy animal feeding restrictions
as described above under Tolerance Assessment ; and, for dciiiestic
use, the restriction not to allow children or pets on treated
surfaces until sprays have dried.
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The 24-t ur reentry interval is being iirip sed for the use of acephate
on aricultural crops, cuui etcially grown orrtamentals, in c tr ercial
or governmental forestry seed production, and in greenhoises.
As described above under Ecological Characteristics , the Agercy
has impsed labeling restrie tions for the protection of endangered
species determined to be in jeopardy froi use of acephate.
5. Sumary ot Major Data Gap
Toxicology Date Due
- Acephate
Rat Repr s tion 39 Months
21—Day Inhalation 6 Months (Pr t col)
Rat Feeding Study 6 Months (Protocol)
— Methylthioacetate (M )
Acute Oral (Rat and Rabbit) 9 Months
Acute Dermal ( Final Report — Rabbit) 9 Months
Acute Inhalation 9 Months
90-Day Dermal (Rabbit) 15 Months
Mutagenicity 12 Months
Envirori 1erital Safety
Avian Residue Monitoring 6 Months (Protocol)
Environmental Fate
Soil Ph )tx egradation 9 Months
Anaerobic Aquatic Metabolisn 27 Months
MsrptioiVDesorptiofl 12 Months
Soil Dissipation - Field 27 Months
Irrigated Crop 39 Months
Confined Rotational Crop 39 Months
Spray Drift 6 Months
Exposure
Applicator (Outd r and Indxr) 6 Months (Protocol)
Indoor Inhabitants 6 Months (Protocol)
Glove Permeability 6 Months (Protocol)
Residue Ch istry
Storage Stability 24 Months
Magnitude of Residues 24 Months
Dairy Cattle Feeding 18 Months
Tobacco Residue 24 Months
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Benefits
Usage 6 Months
Use-Related Exjxsure 6 Months
6. Contact Person at EPA
Wil1i H. Miller (RI 16)
Insecticide—RodentiCide Brar h (TS—767C)
401 M Street S .
Washington, 1X 20460.
DISCLA]JIER: The infoz ation presented in this Chemical Infotniation Fact
Sheet is for informational putpses only and may r t be used to fulfill
data requirements for pestic ide registration and reregistration.
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Attach
Tolerance Changes Reflecting the Recc . led Change in Residue Definition
Acephate* Methainidophos
Established Recommended Established Recommended
Commodity Toleranpe (ppm)a Tolerance (ppm)b Tolerance (ppm)C Tolerance (ppm)C
:;eans (succulent
and dry forms) 3(1) 3 1.
‘ russe1s sprouts 3(0.5) 3 1 1
•auliflower 2(0.5) 2 1 1
elery 10(1) 10 1 1
.ottonseed 2 2 0.1 0.5
:ranberries 0.5(0.1) 0.5 0.1
0.1 0.1 0.01
? f, meat, and
meat byproducts’ 0.1 0.1 0.01
;rass (pasture and
range) 15 15 3
Grass hay 15 15 3
ettuce (head) 10(1) 10 le 1
Iilk 0.1 0.1 0.05
lint hay 15(1) 15 1
eanuts 0.2 0.2 0.1
:‘eanuts hulls 5 5 —— 1.5
‘eppers 4(1) 4 l 1
.oybeans 1 1 0.2
ottonseed hulls 4 4 0.1
ottonseed meals 8 8 2.5
3oybean meals 4 4 2
‘rocessed foodsh 0.02 0.02
Expressed in terms of combined residues of acephate and methamidophos. If specified, limits of methamidophos are
given parenthetically.
Expressed in terms of acephate se only.
Expressed in terms of only methamidophos r se.
‘ Included are cattle, goats, hogs, horses, poultry, and sheep.
The methamidophos tolerance covers all types of lettuce (head and leaf).
The methamidophos tolerance covers all types of peppers.
g Feed additive tolerances in 21 CFR 561.20 (acephate) and recommendations for inclusion under 21 CFR 561.277
(methamidophos).
Food additive tolerance reflecting spot and crack and crevice treatment of food areas of food handling
establishments (21 CFR 193.10). There is no expectation of methamidophos residues in such foods
(residues were nondetectable, < 0.001 pp , in all cases).
* This table does not include the tolerance of acephate in/on macadamia nuts (.05 ppn), which was established
subsequent to completion of the evaluation needed for this Document. Acephate is not currently registered
for use on macadamia nuts.
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