SUBSTITUTE CHEMICAL PROGRAM
INITIAL SCIENTIFIC
MINIECONOMIC REVIEW
CROTOXYPHOS (CIODRIN®)
JUNE 1975
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
CRITERIA AND EVALUATION DIVISION
—V WASHINGTON, D.C. 20460
EPA-540/1-75-015
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This report has been compiled by the
Criteria and Evaluation Division,
Office of Pesticide Programs, EPA,
in conjunction with other sources listed
in the Preface. Mention of trade names
or commercial products does not
constitute endorsement or recommendation
for use.
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PREFACE
The Alternative (Substitute) Chemicals Program was initiated under
Public Law 93-135 of October 24, 1973, to "provide research and testing
of substitute chemicals." The legislative intent is to prevent using
substitutes, which in essence are more deleterious to man and his environ-
ment, than a "problem" pesticide suspected of causing "unreasonable
adverse effects to man or his environment." The major objective of the
program is to determine the suitability of potential substitute chemicals
which now or in the future may act as replacements for those uses (major
and minor) of pesticides that have been cancelled, suspended, or are in
litigation or under internal review for potential unreasonable adverse
effects on man and his environment.
The substitute chemical is reviewed for suitability considering all
applicable scientific factors such as: chemistry, toxicology, pharma-
cology and environmental fate and movement; and socio-economic factors
such as: use patterns and costs and benefits. EPA recognizes the fact
that even though a compound is registered,"it still may not be a practical
substitute for a particular use or uses of a problem pesticide. The
utilitarian value of the "substitute" must be evaluated by reviewing its
biological and economic data. The reviews of substitute chemicals are
carried out in two phases. Phase I conducts these reviews based on data
bases readily accessible at the present time. An Initial Scientific
Review and Minieconomic Review are conducted simultaneously to determine
if there is enough data to make a judgment with respect to the "safety
and efficacy" of the substitute chemical. Phase II is only performed if
the Phase I reviews identify certain questions of safety or lack of benefits.
The Phase II reviews conduct in-depth studies of these questions of safety
and cost/benefits and consider both present and projected future uses of
the substitute chemicals.
The report summarizes rather than interprets scientific- data reviewed
during the course of the studies. Data is not correlated from different
sources. Opinions are not given on contradictory findings. Where applicable,
the review also identifies areas where technical data may be lacking so that
appropriate studies may be initiated to develop desirable information.
This report contains the Phase I Initial Scientific and Minieconomic
Review of Crotoxyphos. Crotoxyphos was identified as a registered
substitute chemical for certain cancelled and suspended uses of DDT.
The review'covers all uses of crotoxyphos and is intended to be adaptable
to future needs. Should crotoxyphos be identified as a substitute for a
problem pesticide other than DDT, the review can be updated and made readily
available for use. The data contained in this report was not intended to be
iii
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complete in all areas. Data-searches ended in December, 1974. The review
was coordinated by a team of EPA scientists in the Criteria and Evaluation
Division of the Office of Pesticide Programs. The responsibility of the
team leader was to provide guidance and direction and technically review
information retrieved during the course of the study. The following EPA
scientists were members of the review team: Richard K. Tucker (Team
Leader); Merry Lou Alexander (Chemistry); 0. E. Paynter, Ph.D. (Pharmacology
and Toxicology); Richard Claggett (Fate and Significance in the Environment);
E. David Thomas, Ph.D. (Registered Uses); Jeff Conopask (Economics).
Data research, abstracting, and collection were primarily performed by
Midwest Research Institute (MRI), Kansas City, Missouri (EPA Contract
#68-01-2448) under the direction of Mr. Thomas L. Ferguson. RvR Consultants,
Shawnee Mission, Kansas, under a subcontract to MRI, assisted in data
collection. The following MRI scientists were principal contributors to
report: Chester R. Crawford, Ph.D., John Doull, Ph.D, David F. Hahlen,
William B. House, Ph.D., Alfred Meiners, Ph.D. Rosmarie von Rumker, Ph.D.
(RvR Consultants) also contributed to the report.
Draft copies of the report have been reviewed by the scientific staffs
of EPA's National Environmental Research Centers and their associated
laboratories. Comments and supplemental material provided by the following
laboratories are greatly appreciated and have been incorporated into this
report: Gulf Breeze Environmental Research Laboratory, Gulf, Gulf Breeze,
Florida and National Ecological Research Laboratory, Corvallis, Oregon.
Shell Chemical Company, a manufacturer of crotoxyphos, reviewed the draft
of this report and made certain comments and additions.
iv
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GENERAL CONTENTS
Page
List of Figures vi
List of Tables vii
Part I. Summary 1
Part II. Initial Scientific Review 11
Subpart A. Chemistry 11
Subpart B. Pharmacology and Toxicology ... 31
Subpart C. Fate and Significance in the Environment 57
Subpart D. Production and Use 71
Part III. Minieconomic Review 89
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FIGURES
No. Page
1 Analytical Scheme for Chlorinated (Nonionic and
Organophosphate Residues 19
vi
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TABLES
No. Pa8e
1 Acute Oral Toxic ity of Crotoxyphos to Rats ......... 33
2 Acute Toxicity of Crotoxyphos for Rats via
Routes Other Than Oral .................. 35
3 Acute Inhalation Toxicity of Crotoxyphos to Rats ...... 37
4 Subacute Oral Toxicity Test in Rats ............ 38
5 Subacute Toxicity of Crotoxyphos to Rats .......... 39
6 Acute Oral Toxicity of Crotoxyphos to Mice ......... 40
7 Acute Oral Toxicity of Crotoxyphos to Chicks ........ 42
8 Subacute Oral Toxicity Test in White Leghorn Cockerels ... 42
9 Subacute Oral Toxicity Test in Dogs ............ 43
10 Acute Dermal Toxicity to Rabbits .............. 44
11 Acute Dermal Toxicity of Crotoxyphos to Some
Domestic Species ..................... 45
12 Comparative Dermal Toxicity to Cattle ........... 46
13 Subacute Dermal Toxicity of Crotoxyphos to Pigs and Cattle . 48
14 Subacute Dermal Toxicity to Horses ............. 50
15 Acute and Subacute Toxicity of Technical Crotoxyphos to
Fish ........................ . . . 59
16 Crotoxyphos 21.5% Spray Concentrate Label ......... 75
17 Crotoxyphos 1% + Dichlorvos 0.23% Fly Spray Label ..... 76
18 Proportions of Crotoxyphos Consumption for Different
Livestock Uses in the U.S. in 1966 and 1971 ....... 82
19 Estimated Proportions of Crotoxyphos Consumption for
Different Livestock Uses in the U.S. By Regions, 1971 . . 84
20 Crotoxyphos Uses in California by Crops and Other Uses,
1970-1973 ........................ 85
vii
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PART I. SUMMARY
CONTENTS
Page
Production and Use 2
Toxicity and Physiological Effects . .
Food Tolerances and Acceptable Intake
Environmental Effects
Limitations in Available Scientific Data 8
Efficacy and Cost Effectiveness
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This section contains a summary of the "Initial Scientific and
Minieconomic Review" conducted on crotoxyphos (Ciodrin Qv , alpha-
methylbenzyl 3-hydroxycrotonate dimethyl phosphate). The section
summarizes rather than interprets scientific data reviewed.
Production and Use
Crotoxyphos is manufactured in the United States by Shell Chemicj
Company, a division of Shell Oil Company, under the tradename Ciodrin'
One process that has been reported for its manufacturer involves the
following three-step reaction sequence:
0 0
CH3-C-CH2-C-OCH3
Methyl acetoacetate
1-phenylethanol
0 0
}-C-CH2-ci-0-CH-CH3
CHOH
1-phenylethyl
acetoacetate (I)
0 0
CH3-C-CH2-C-0-CH-CH3 + S02C12
Sulfuryl
(I) fC\] chloride
00.
> CH3-C-CH-C-0-CH-CH3
S0
CHI
1-phenylethyl
aIpha-chloro-acetoacetate
(ID
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Cj
CH3-C-Cll-C-0-CH-CH3
Cl
OCH3
P-OCH
(ID
OCH3
Trimethyl
phosphite
The chemical properties of crotoxyphos are similar to those of many
other organophosphates. It readily undergoes hydrolysis. This hydrolysis
is more rapid in basic than in acidic aqueous systems; the half-life is
180 hr at pH 9, 410 hr at pH 6, and 540 hr at pH 2. In soils, the degra-
dation rate of crotoxyphos is even more rapid, i.e., about two orders of
magnitude faster than the above hydrolysis rates.
Technical crotoxyphos is a liquid of over 80% purity. The major
formulations of crotoxyphos are emulsifiable concentrates, (1 to 3.2 lb/
gal), ready-to-use solutions (1 to 3%), and dusts (3%). A 20% dust
concentrate is also available for further formulation. Crotoxyphos is
often formulated with other insecticides.
Crotoxyphos is used to control various types of flies, ticks, lice
and certain mites around livestock. About 80% of the total domestic
usage, however, is estimated to be on dairy cattle. Crotoxyphos is
also used on beef cattle, hogs and sheep. It is not used on crops.
The estimated domestic use of crotoxyphos in 1971 was 901,000 lb of
active ingredient, compared to only 141,000 lb in 1966. By geographic
region, the North Central states were estimated to use 50% of the total
1971 usage, followed (in decreasing order of use) by the Northeast,
South Central, Southwest, Southeast, and Northwest states. An assess-
ment of supply increase potential is currently not possible.
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Toxicity and Physiological Effects
Crotoxyphos is a toxic organophosphate insecticide. The toxicity
of crotoxyphos to rats is as follows:
Route of entry Measurement Value
Oral LD50 38.4-125 mg/kg
Dermal 0)50 202-375 mg/kg
Subcutaneous LD50 148.8 mg/kg
Inhalation LC50 (1 hr) 670 mg/liter
Crotoxyphos in the diet of rats up to 250 ppm caused no inhibitory
effect on brain cholinesterase. Feeding at a level of 750 ppm, however,
caused a marked depression. Microscopic examination of tissues from
animals exposed to all dose levels revealed no pathological changes due
to crotoxyphos.
The cholinesterase "no effect" level appears to be 7 ppm for rats.
Crotoxyphos fed in the diet of rats for 10 months at the level of
0.01 mg/kg caused no effects on cholinesterase activity. However, feeding
3.84, 1.92, and 0.77 mg/kg caused inhibition of cholinesterase activity,
increase in vitamin C levels in liver and kidney, and reduced rate of
hippuric acid synthesis.
Acute oral LD5Q reported for mice ranges from 39.8 to 89 mg/kg.
The acute oral LD5Q of crotoxyphos to cats is 802 mg/kg.
The LD^Q of crotoxyphos to chicks has been reported to be 111 mg/kg
and for hens, 147 mg/kg. A one-week feeding study of chicks at levels
of 50, 100, 200, and 400, and 800 ppm crotoxyphos in the diet showed
that 800 ppm caused a 50% inhibition of plasma cholinesterase.
Crotoxyphos does not appear to induce demyelination of peripheral
nerves of chicken.
Feeding crotoxyphos in the diet of dogs for 12 weeks at levels of
5, 15, and 45 ppm caused no effect on growth or organ weights at any
level of exposure. However, 15 and 45 ppm caused a depression of plasma
and RBC cholinesterase activity. Feeding 135 ppm for 2 weeks did not
affect brain cholinesterase. Microscopic examination of tissues at all
dose levels in the 12 week study revealed no pathological changes that
could be attributed to crotoxyphos. The cholinesterase "no effect"
level in dogs appears to be 5 ppm.
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Numerous studies have been undertaken to determine the safety of
crotoxyphos to a variety of domestic animals. Sheep and goats were
dipped in 1% emulsion of crotoxyphos. Swine and young dairy calves
were sprayed with 0.5 and 2% emulsions. The only signs of toxicity
were diarrhea and muscular weakness in some dairy calves when sprayed
with the 2% emulsion.
Yearling cattle, adult cattle, horses, and pigs have also been
exposed to various concentrations of dips and sprays, for varying
lengths of time. Pigs, horses and adult cattle exhibited cholinesterase
depression during treatment or post-treatment period.
The metabolism of crotoxyphos can be summarized as follows:
1. Crotoxyphos is absorbed from the gastro-intestinal tract and
from intact skin in mammals.
2. The deesterified carboxylic acid of crotoxyphos is a minor
metabolite with weak cholinesterase-inhibiting activity.
3. The major metabolites of crotoxyphos are dimethylphosphoric
acid, acetoacetic acid and hydroxyethylbenzene.
Crotoxyphos feed to pregnant cattle failed to produce abortions.
Crotoxyphos failed to induce reverse mutation in Escherichia coli
W?2 on solid medium.
Crotoxyphos did not cause any teratogenic effects in embryos when
eggs were injected on day 4 or day 5 of incubation.
No data was found on oncogenic effects of crotoxyphos or effects
on humans.
Food Tolerances and Acceptable Intake
In the United States, tolerances for crotoxyphos have been estab-
lished for meat, fat and meat by-products of cattle, goats, hogs and
sheep, and for milk. All tolerances are 0.02 ppm. An acceptable
daily intake (ADI) has not been established for crotoxyphos. Crotoxyphos
has not been reported as a significant residue in any class of food.
However, analytical systems routinely used by Food and Drug Administration
laboratories to monitor pesticide residues in food and feedstuffs do
not detect crotoxyphos. Thus, absence of crotoxyphos residue data does
not necessarily mean that it is not present.
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Environmental Effects
An evaluation of crotoxyphos toxicity to fish and other aquatic species
is summarized as follows:
Species
Exposure
Time Toxicity
(hr) Calculation
Toxicity Measure
(ppb)
Sheepshead
(Cyprinodon variegatus)
Bluegill
(Lepomis macrochirus)
Channel catfish
(Ictalurus punctatus)
Cutthroat trout
(Salmo clarki)
Rainbow trout
(Salmo gairdneri)
Fathead minnow
(Pimephales promelas)
Largemouth bass
(Micropterus salmoides)
Brown shrimp
(Penaeus aztecus)
Eastern oyster
(Crassostrea virginica)
Scud
(Gammarus lacustris)
Stonef ly
(Pteronarcys sp_. )
24
48
24
96
24
96
24
96
24
96
24
96
24
96
24
48
96
24
48
96
24
96
EC50
EC50
LC50
LC50
LC50
^50
LC50
LC5Q
LC
^50
LC50
' LC50
%
EC50
EC50
no adverse
LC50
^50
LC5Q
LC50
LC50
>1,000
>1,000
390
152
3,700
2,600
92
51
101
72.4
15,500
11,900
1,800
1,100
220
32
affect at 1,000
49
29
15
1.0-10
1.0-10
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The only data found on the effects of crotoxyphos on wildlife was
acute oral LD^Q of 790 rag/kg for young mallard drakes (Anas platy-
rynchos).
Commercial labels of insecticides that contain crotoxyphos as the
active ingredient contain the warning: "This product is toxic to fish
and wildlife."
Crotoxyphos has been shown to be "moderately toxic" to the honeybee
(Apis mellifera). The LD5Q value, based on contact effect, was 2.26 ug/bee
for 48 hr exposure at 80°F and 65% relative humidity.
No data was found on the effect of crotoxyphos on lower terrestrial
organisms.
The degradation of crotoxyphos has been evaluated in nonsterilized
and sterilized samples of three different soils, Poygan silty clay loam
(33.6% clay; 10.0% organic matter; pH 7.2); Kewaunee clay (48.7% clay;
3.8% organic matter; pH 6.4); and Ella loamy sand (5.2% clay; 1.6%
organic matter; pH 3.8). The half-lives (in hr) of crotoxyphos in these
soils were as follows:
Poygan Kewaunee Ella loamy
silty clay loam clay sand
Nonsterilized 2.00 5.50 71.0
Sterilized 3.75 6.00 77.0
Studies concerning the pathways of chemical breakdown of crotoxyphos
indicated that dimethylphosphoric acid, cis-hydroxycrotonic acid, and
1-phenylethanol are the final degradation products in soils.
Half-lives of crotoxyphos in aqueous systems (temperature not
specified) are reported as: 540 hr at pH 2; 410 hr at pH 6; and 180 hr
at pH 9. At 100°F, the half-life is 35 hr at pH 9 and 87 hr at pH 1.
No data was found on crotoxyphos residues in water, air, or non-
target plants or on its bioaccumulation, biomagnification, or environ-
mental transport.
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Limitations in Available Scientific Data
The review of scientific literature was based on available sources
given limitations of time and resources.
Data was not found in a number of pertinent areas:
1. Acute toxicity of both technical and formulated crotoxyphos
(eye irritation to rabit, primary skin irritation to rabbit, and inhalation
LCcQ for at least two species in a dynamic flow system ).
2. Subacute inhalation to rats. (If cattle are to be sprayed in
confined areas, a subacute inhalation test should be carried out.)
3. Data on the environment effects of crotoxyphos, including effects
on fish, lower aquatic organisms, wildlife, cattle metabolism, beneficial
arthropods, and lower terrestrial organisms.
4. Data on the presence, fate, and persistence of crotoxyphos
residues in water, sediment, and other elements of aquatic ecosystems.
5. Data on the presence, fate, and persistence of crotoxyphos
residues in air.
6. Data on bioaccumulation, biomagniflcation, or environmental
transport mechanisms.
Efficacy and Cost Effectiveness
Crotoxyphos is an organophosphate insecticide that is used primarily
for control of biting flies, ticks, and lice on cattle. Its effectiveness
depends upon the method of application, number of applications, concen-
tration, and point of application on the animal.
Good control of horn flies on cattle was achieved with a variety of
application devices. One application every 3 to 5 days provided good
control when applied with a low volume sprayer. Dust bags containing 3%
crotoxyphos gave good control when they were frequently contacted by the
cattle. Back rubbers also provide good control of horn flies'. Stable
flies on cattle are effectively controlled with crotoxyphos. However,
crotoxyphos does not appear to give any residual control and must be
applied daily.
Face fly control of up to 85% can be achieved on cattle with back
rubbers or dust bags containing crotoxyphos. Frequent contact by the
animal is necessary for control. Economic benefits from the control of
flies on beef cattle range from a loss of 2.3c/day/head to a gain of
25.0£/day/head. -For dairy cows, the economic benefits range from a loss
of 34.4
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Crotoxyphos gives 99 to 100% control of cattle ticks and gives good
residual control for 3 weeks. Control of the lone star tick for up to
1 week can also be achieved with crotoxyphos. Complete control of winter
ticks on cattle and horses has been achieved with crotoxyphos. Similar
results were experienced with horse ticks. A 2% crotoxyphos oil reduced
cattle grubs on cattle by 74 to 96%. Chorioptic mange mites and several
biting lice were completely controlled by crotoxyphos for up to 6 weeks.
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PART II. INITIAL SCIENTIFIC REVIEW
SUBPART A. CHEMISTRY
CONTENTS
Page
Synthesis and Production Technology 12
Physical Properties 15
Analytical Methods 17
Multi-Residue Methods 17
Residue Analysis Principles 20
Formulation Analysis Principles 22
Composition and Formulation 23
Chemical Properties, Degradation Reactions and Decomposition
Processes 23
Hydrolysis 23
Other Chemical Reactions 25
Occurrence of Crotoxyphos in Food and Feed Commodities 26
Acceptable Daily Intake 26
Tolerances 26
References 27
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This section contains a detailed review of available data on the
chemistry and presence of crotoxyphos in foods. Eight subject areas have
been examined*. Synthesis and Production Technology; Physical Properties of
Crotoxyphos; Analytical Methods; Composition and Formulation, Chemical
Properties, Degredation Reactions and Decomposition Processes; Occurrence
of Residue in Food and Feed Commodities; Acceptable Daily Intake and
Tolerances. The section summarizes rather than interprets data reviewed.
Synthesis and Production Technology
Crotoxyphos is manufactured in the United States by the Shell
Chemical Company. According to Porter (1967)-' crotoxyphos is prepared
by the following reaction sequence:
0 0 . \ CH3
CH3-C-CH2-C-OCH3 + /Q\—CH-OH
Methyl acetoacetate > ' 1-phenylethanol
v v
CH3-(!-CH2-C-0-CH-CH3 + CH3OH
1-phenylethyl
acetoacetate (1)
0,
0
CH3-C-CH2-C-0-CH-CH3
Sulfuryl
(I) JVVl chloride
o 9
CH3-C-CH-C-0-CH-CH3 + S02 t HC1
l
Cl
1-phenylethyl alpha-
chloroacetoacetate (II)
I/ Porter, P. E., "Ciodrin® Insecticide," Analytical Methods for Pesti-
cides, Plant Growth Regulators, and Food Additives, Vol. V, Additional
Principles and Methods of Analysis. Chap. 11, Academic Presa>Inc.,
New York (1967).
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OCH3
CH3-C-CJS-C-0-CH-CH3 + P-OCH3
Cl /-^ \
(II) fOl OCH3
Trimethyl phosphite
Crotoxyphos
The preceding procedure represents the most likely production
method, but no production details are available. The Shell Oil Company
owns patents on the compound (as a composition of matter) and has patents
on methods for its production. (Whetston and Barman, 1960; Whetstone
and Stiles, 1961; Tieman and Stiles, 1962; Whetstone and Harman, 1963) .il
The patented production method is essentially as has been described.
I/ Whetstone, R., and D. Harman, "Insecticidally Active Esters of Phosphorus
Acids and Preparation of the Same," U.S. Patent No. 2,956,073 (to
Shell Oil Company, 11 October 1960).
2_/ Whetstone, R., and A. R. Stiles, "Arylphosphate Compounds," U.S. Patent
No. 2,982,686 (to Shell Oil Company, 2 May 1961).
3/ Tieman, C. H., and A. R. Stiles, "Preparation of Vinyl Esters of Phos-
phorus Acids Useful as Insecticides," U.S. Patent No. 3,068,268
(to Shell Oil Company, 11 December 1962).
4/ Whetstone, R., and D. Harman, "Organo-Phosphorus Insecticide," U.S.
Patent No. 3,116,201 (to Shell Oil Company, 31 December 1963).
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U.S. Patent 3,068,268 (Tieman and Stiles, 1962) outlines an Improved
process for preparing crotoxyphos. Essentially, this process involves the
toxification step (3) for the purpose of increasing the yield of the more
active (E) isoner of crotoxyphos.
According to Beynon et al. (1973)17, the terms E and Z are used to avoid
confusion with the terms cis and trans based on other conventions. In order
to determine the configuration of a double bond, it is necessary to determine
which two groups attached to the double bond have the higher priority. The
determination of the priority of the groups according to sequence rules is
straightforward for crotoxyphos. One need only consider the atomic numbers
of the atoms attached directly to the carbon atoms of the double bond. For
crotoxyphos, one must consider the atomic numbers of the four atoms in
parentheses.
(8) (1)
-0
(6) (6)
E-isomer of crotoxyphos
The sequence rules are based on the atomic numbers of the atoms; the
atoms of higher atomic number have higher priority. The oxygen atom
has the highest priority on the one carbon atom of the double bond and
the carbon atom has the highest priority on the other. Thus, for such
a structure, the configuration is described in terms of the oxygen and
carbon atoms. The structure with these atoms on the same side of the
double bond is called Z ("Zusammen," together) and that with them on the
opposite side is called E ("Entgegen," opposite). The more-active
isomer of crotoxyphos has the E configuration.
7 /
Melnlkov (1971)±./ also reports the above reaction sequence, but states
that another method can be used for the production of crotoxyphos:
0
CH3C=CHC02 (CH30)2POC=CHC02CHC6H5 + NaCl
0«a CH3 CH3 CH3
sodium enolate of dimethylchloro- crotoxyphos
phenylethyl phosphate
acetoacetate
I/ Beynon, K. I., D. H. Hut son, and A. N. Wright, "The Metabolism and Degrada
tion of Vinyl Phosphate Insecticides," Residue Rev., 47:55-142 (1973).
2/ Melnikov, N. N., Chemistry of Pesticides, Vol. 36 of Residue Rev..
Springer-Verlag, New York (1971).
14
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Physical Properties
Common Name; Crotoxyphos
Trade Name; Ciodrii$>
Chemical Name; Crotoxyphos has acquired many chemical names in the
dozen years of its commercial use. The following is
a list of them:
Caswell et al. (1972).I/ Martin (1971),!/ [U.S. designation] and
Shell (1962)1/ [alternate]
Dimethyl phosphate of alpha-methylbenzyl 3—hydroxy-cis-crotonate
Caswell et al. (1972) and Fukuto and Sims (1971)j/
Alpha-methylbenzyl 3-hydroxycrotonate dimethyl phosphate
Metcalf (1971)1/
0,0-Dimethyl 0-[l-methyl-2-(l-methyl-2-(l-Phenylcarbethoxy) vinyl]phosphate
Merck Index (1968)j/
3-Hydroxycrotonic acid, oHaethylbenzyl ester dimethyl phosphate
Shell (1962) and Beynon et al. (1973) [alternate]
Alpha-methylbenzyl 3—(dimethoxyphosphinyloxy)-cis_-crotonate
Chemical Abstract Service
(1971 and earlier) crotonic acid, 3-hydroxy-o/-methylbenzyl ester
dimethyl phosphate
(1972 and later) 2-butenoic acid, 3-[dimethoxyphosphinyloxy]-l-
phenylethyl ester (E)
Bevnon et al. (1973)
(IDPAC) dimethyl 2-(ok-methylbenzyloxycarbonyl)-l-methylvinyl
phosphate (alternate) l-methylbenzyloxy-l-propen-2-yl dimethyl
phosphate
I/ Caswell, R. L., D. E. Johnson, and C. Fleck, Acceptable Common Names
and Chemical Names for the Ingredient Statement on Pesticide Labels
(2nd ed.), Environmental Protection Agency, Washington, D.C. (June 1972).
2J Martin, H. , Pesticide Manual, British Crop Protection Council, 2nd ed.
fa
3/ Shell Chemical Company, "Summary of Basic Data for Technical Ciodrin®
Insecticide," Technical Bulletin, San Ramon, Calif. (1962).
4/ Fukuto, T. T., and J. J. Sims, "Metabolism of Insecticides and Fungicides,"
In: R. White Stevens (ed.): Pesticides in the Environment. Marcel
Dekker, Inc., New York (1971).
51 Metcalf, R. L., "Chemistry and Biology of Pesticides," In: R. White Stevens
(ed.): Pesticides in the Environment. Marcel Dekker, Inc., New York
(1971).
6/ Merck Index, The, P. G. Strecher (ed.), 8th ed., Merck and Co., Kahway, N.J.
(1968) .
15
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Pesticide Class; Insecticide; organophosphate
Structural Formula:
0
A ?fl
CH30 0-C=C-C-0-C
CH3 H
Empirical Formula;
Molecular Weight: 314.28
Analysis: C - 53.50%; H - 6.09%; 0 - 30.55%; P - 30.55%
Data below is for Technical Grade Ciodrin®, approximately
85% pure.
Physical State; light straw colored liquid with mild
ester odor
Specific Gravity: 1.2 at 60°F
Density; 10 Ib/gal at 68 °F
Boiling Point; 135°C at 0.03 mm Hg
Vapor Pressure; (mm Hg) Temperature (°C)
1.4 x 10'5 20
3.9 x 10-5 30
9.8 x 10~5 40
Refractive Index: njj5 =1.50
Pour Point: Below 0°F
Flash Point: Over 175 °F (tag open cup)
Flammability; Nonflammable
Solubility: Slightly soluble in water (0.1% at 25°C). Slightly
soluble in kerosene and saturated hydrocarbons.
Soluble in acetone, ethanol, isopropanol, chloroform
and other highly chlorinated hydrocarbons. Miscible
with xylene. Partition coefficient, hexane: water < O.OSc
16
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Corrosive Action: Slightly corrosive to mild steel and bare metals;
noncorrosive to stainless steel 316, raonel and
aluminum 3003. Will not attack rigid PVC, fiber-
glass, reinforced polyester, or most organic
linings.
Stability; Stable when stored in glass, polyethylene, or certain
lined containers; stable in presence of hydrocarbon
solvents. Formulations are unstable on most solid
carriers. See Chemical Properties section for action
in water, acids and bases.
Analytical Methods
This subsection reviews analytical methods for crotoxyphos. The
review describes multi-residue methods, residue analysis principles, and
formulation analysis principles. Information on the sensitivity and
selectivity of these methods is also presented.
Multi-Residue Methods - The Association of Official Analytical Chemists
methods manual!' does not contain multi-residue methods for detecting
crotoxyphos. Limited data is available in the Pesticide Analytical Manual,
Volume I, (PAM, 1971).U
The multi-residue analytical system used by FDA laboratories (in
Kansas City, Missouri) does not detect crotoxyphos since special techniques
are required for its detection. Ordinarily, if the FDA does not expect
to find a particular pesticide, they do not perform the specific method-
ology necessary to detect it. However, some multi-residue methods for
crotoxyphos have been investigated.
\J Association of Official Analytical Chemists, Official Methods of
Analysis of the Association of Official Analytical Chemists, llth ed.,
Washington, D.C. (1970).~~
2J U.S. Department of Health, Education, and Welfare, Food and Drug
Administration, Pesticide Analytical Manual. Vol. I (1971).
17
-------
The general PAM multi-residue methods analytical scheme for organo-
phosphate residues is illustrated in Figure 1. According to the manual,
no data is available concerning the recovery of crotoxyphos from fatty
foods when the Florisil column clean up procedure is used (See Figure 1).
The PAM also states that crotoxyphos is not recovered from nonfatty foods;
recovery is not achieved by elution of the Florisil column with 6%, 15%
or 50% ethyl ether - petroleum ether. However, Beckman and Barber (1969)!/
report an 86% recovery of crotoxyphos from Florisil using acetone as an
elutant material.
Watts and Storherr (1969)Z./ have provided retention times and
response data for over 60 organophosphorus pesticides on three gas
chromatograph columns. (This data is cited by Zwieg and Sherma,3/
and by the Pesticide Analytical Manual.) The data is summarized
below:
Column Retention time Sensitivity
packing relative to parathion/ (ng for 1/2
107. DC-200 1.36 12
or 10% DC-200,
15% QF-1 (1:1 w/w)*
10% DC-200, 15% 1.38 35
QF-1*
2% DECS (stabilized), 1.81 10
column temperature 210°C
* At 200°C, nitrogen flowrate 120 ml/min
/ Potassium Chloride thermionic detector
f FSD = Full scale deflection
I/ Beckman, H., and D. Garber, "Recovery of 65 Organophosphorus Pesticides
from Florisil with a New Solvent Elution System," J. Assoc. Off.
Anal. Chem.. 52(2):286-293 (1969).
21 Watts, R. R., and R. W. Storherr, "Gas Chromatography of Organophosphorus
Pesticides; Retention and Response Data on Three Columns," J. Assoc.
Off. Anal. Chem.. 52(3):513-521 (1969).
3_/ Zweig, G. and J. Sherraa, Analytical Methods for Pesticides and Plant
Growth Regulators, Vol. VI: Gas Chromatographic Analysis, p. 218,
Academic Press, Inc., New York (1972).
18
-------
1
Fatty Food*
211 231
1
Extraction of Fat
211.13
1
Acetonilrile
Partitioning
211.14
1
1
1
-J
J 2nd Florisil
1 Column ...
} 211.16a ***•*
T
1 * '
{ Acid-Cclite
i Column- ^0
\ 211.16 b ~-'~~
i & 2nd Florisil
! Column
•
Chlorinated (Noiuonic) 210*
Orgaitophonuhatcs 230
1
Proximate Percentage Water
and Fat in Food* and Feeds 202
1
1
Non Fatty Foods
212 232
Extraction and
Partitioning
212.13
1
Florisil Column
211.15
1 _j
1 IMfcFl
1 * Mualc
1
5 2™t florin il
Gas Chroma t.^raphy | Column
Electron Capture and 1 Thermionic — , ""*" 1 211.16 a
j MfO-Celne
, Cos Chromatography \^,--~~~~l Column
•\ Electron Capture Detector | | 211 16 c
! 3n Jv L ", -.
J *» I
•» ^_ _ _ - - J. ...
%% Alkaline
\l Hydrolysis
211.16 d
& UgO-Celitc
I Column
|
1
Thin Layer Chromatography
Chlorinated 410
Organophosphatea 430
i
i
i
•
i
•
•
•
i
i
j
j
* The numbers, refer to the decimal numbering system of PAM. The
primary analytical scheme is in bold type. Additional cleanup
and/or quantitation schemes are in italics. (Source: PAM, 1971)
Figure 1
ANALYTICAL SCHEME FOR CHLORINATED (NONIONIC AND ORGANOPHOSPHATE RESIDUES)
19
-------
Bowman and Beroza (1970)-i/ have provided retention times for
crotoxyphos and 137 other pesticides and metabolites. Crotoxyphos
data is presented as follows:
Relative retention time
Liquid (parathion = 1.00)
phase Isothermal Temperature programmed
OV-101 1.27 1.14
OV-17 1.44 1.16
OV-210 1.33 1.14
OV-225 1.23 1.07
This data was obtained using a gas chromatograph equipped
with a flame photometric detector. Glass columns were packed with 5%
w/w of the liquid phases on 80 to 100 mesh Gas Chrom Q and conditioned
overnight at 320°C. Nitrogen (carrier) gas flow rate was 160 ml/min.
Injection port temperature was 225°C, detector 280°C, column 200°C
(isothermal) or programmed to start at 150°C, increase at 10°C/min
for 15 min, and then held at 300°C until the last peak emerged.
Residue Analysis Principles - PAM (Vol. II, 1971)—' does not contain a
specific residue analysis method for crotoxyphos.
Zweig and Sherma (1972) have recommended a gas chromatographic
method of residue analysis for crotoxyphos. This is the same method
used by Shell.I/ The method is suitable for residues in animal
tissues and milk. The residue is extracted from tissue with acetone
or from milk with acetone and sodium sulfate. The extract is con-
centrated, partitioned into ethyl ether, further concentrated, and
then exchanged into ethyl acetate. This solution is analyzed by
gas chromatography using a flame photometric or alkali flame ionization
detector system. Concentrations as low as 0.03 ppm can be determined,
but the accuracy is not stated in the method.
I/ Bowman, M.C., and M. Beroza, "GLC Retention Times of Pesticides and
Metabolites Containing Phosphorus and Sulfur on Four Thermally
Stable Columns," J. Assoc. Off. Anal. Chem., 53(3):499-508 (1970)
21 U.S. Department of Health, Education, and Welfare, Food and Drug
Administration, Pesticide Analytical Manual, Vol. II (1971).
3_/ Shell Development Company, Biological Sciences Research Center,
Modesto, Calif., MMS-R-268-1 (April 1971).
20
-------
The recommended method of Porter (1967) Is a cholinesterase-
Inhibltion method, and is the same method used by Shell (1964).!/
This method has only been tested for the determination of crotoxyphos
in animal tissue or animal products. The residue is first extracted
with a solvent suitable to the animal product, partitioned into ace-
tonitrile, and then into hexane. A portion is washed to remove water-
soluble interferences and then analyzed by a cholinesterase method.
The accuracy of the method is not stated.
Porter (1967) commented on three other methods. He reports that
experience with gas chromatographic analysis of crotoxyphos has been poor
owing to its low volatility and relatively rapid degradation. Another
method, thin-layer chromatography, has been used for semiquantitative
determination of crotoxyphos. A third satisfactory method has been
insect bioassay.
Oehler and Claborn (1970)2/ have described a gas chromatographic
method in the Journal of the AOAC. This method may be used for body
tissue or milk. Extraction procedures varied slightly depending upon
material, but usually involved hexane or hexane and acetone. The residue
was then partitioned into acetonitrile. The gas chromatograph had a
flame photometric detector. Recoveries varied from 80 to 98%. Residues
as low as 0.003 ppm were detectable.
Another method was described by Westlake et al. (1969a, 1969b).LA/-
The two articles give different ways of making the final determination,
but both used acid hydrolysis followed by oxidation to convert cro-
toxyphos to acetophenone. The acetophenone is microdisttiled, then
extracted into carbon tetrachloride. For the final determination,
Westlake et al. (1969a) used a spectrophotometer and measured the carbonyl
peak at 1,690 cm"1. Recoveries ranged from 82 to 1317. and the lower
limit of determination was 20 ug of crotoxyphos.
T7Shell Development Company, Agricultural Research Division, Analytical
Methods MMS-38/64 (July 1964).
2/ Oehler, D. D., and H. V. Claborn, "Determination of Crotoxyphos in
Milk and in the Body Tissues of Cattle and Pigs," J. Assoc. Off.
Anal. Chem., 53(5):1045-1047 (1970).
3_/ Westlake, A., F. A. Gunther, and W. E. Westlake, "Conversion of the
Insecticide Ciodrin to Acetophenone for Microdetermination," J^
Agr. Food Chem.. 17(6):1157-1159 (1969a).
4/ Westlake, A., F. E. Hearth, F. A. Gunther, and W. E. Westlake,
"Determination of Ciodrin from Fortified Animal Tissues by
Oscillopolarography of Its Conversion Product Acetophenone," J.
Agr. Food Chem.. 17(6):1160-1163 (1969b).
21
-------
In a variation of this method, Westlake et al. (1969b) made the final
determination using oscillopolarography. In this test they began with
animal tissue, milk or eggs containing crotoxyphos as a residue. Re-
coveries ranged from 40 to 1097., but were more consistent in a specific
product category. Polarography cannot be used on residues in liver
because of interferring compounds.
Formulation Analysis Principles - Porter (1967) states that the recommended
method for formulation analysis employs infrared spectrophotometry. Liquid
formulations, such as emulsiftable concentrates or technical grade crotoxy-
phos, are simply dissolved in carbon disulfide and the absorbance is measured
at a characteristic band of 11 jim. Solid formulations are first extracted
with chloroform, and the crotoxyphos is then taken into carbon disulfide.
The accuracy of the method is not given, but it depends upon the absence
of materials which absorb radiation near 11 urn. This method is similar
to the method of Czech (1964)*!/
Porter (1967) also mentions three other possible methods. The
first, which consists of an analysis for total phosphorus, is often
used in formulation production. Phosphorus in crotoxyphos is separated
from that in degradation products by partitioning between water and
chloroform; the quantity of phosphorus in the chloroform phase is then
determined. A second method employs gas chromatography with detection
by thermal conductivity. A third method consists of measuring cholines-
terase inhibition. This method is generally unattractive for macro-
analysis because of the high dilutions required and because poor pre-
cision is achieved.
Zweig and Sherma (1972) present details of a gas chromatographic
method. Emulsifiable concentrates are diluted with chloroform and
dust formulations are extracted with chloroform. Any suitable gas
chromatograph with a flame ionization or thermal conductivity detector
may be used. The precision of the method is estimated to be ± 4% of
the mean.
The Shell Development Company (1971)2./ describes a gas chromato-
graphic method for the determination of crotoxyphos in dusts and resin
concentrates. It differs from the Porter (1967) method. In the
Shell method, the sample is extracted with chloroform, and is sub-
jected to gas chromatographic analysis under conditions which sufficiently
separate the E and Z isomers. Crotoxyphos, the E isomer, can then be
determined. The accuracy of the method is not stated.
T7Czech, F. P., "Analysis of Insecticides in Aqueous Emulsions Used in
Livestock Dips and Sprays: General Infrared Method,-11 J. Assoc. Off.
Agr. Chem., 47(5):829-837 (1964).
2/ Shell Development Company, Biological Sciences Research Center,
Modesto, Calif., MMS-C-298-1 (November 1971).
22
-------
Composition and Formulation
Technical CiodrinQjy according to its only domestic manufacturer is
over 80% crotoxyphos (Shell, 1962). The remaining percentage is not
identified. The concentrations of the more active and less active
isomers are also not disclosed.
Crotoxyphos is available in a variety of formulations and strengths.
Among those listed by the manufacturer are: 1) emulsifiable concentrates,
1.1, 2.0 and 3.2 Ib/gal; 2) solutions, ready-to-use; 1 and 2%; 3) dusts,
3%,ready-to-use; 20% for further formulation.
Technical crotoxyphos is also formulated and used with other insec-
ticides. .A "dairy and livestock" spray contains 10% crotoxyphos and 2.3%
dichlorvos; no information was available concerning synergistic effects.
According to Porter (1967) the stability of crotoxyphos is poor
on most solid carriers and care must be exercised in preparing solid
formulations.
No information is available concerning the nature of the degradation
products. The manufacturer did not provide the nature of the carriers
employed in the various formulations.
Chemical Properties, Degradation Reactions and Decomposition Processes
Crotoxyphos is an ester of phosphoric acid, contains a vinyl phos-
phate structure and is also an ester of crotonic acid. Its known chemical
reactions could be predicted for a compound of this structure.
Most of the available information concerning the chemical reactions
of crotoxyphos deals with hydrolysis; no information was found concerning
oxidation or photolysis.
Hydrolysis - Like other organophosphate compounds, crotoxyphos readily
undergoes hydrolysis. Hydrolysis occurs in acidic or basic solution, ,
but is much more rapid in basic solution. Konrad and Chesters (1969)—
determined the following half-lives for hydrolysis at various values of
pH. The initial pH was adjusted using HC1 or NaOH and the solution was
not buffered. The temperature was unspecified.
p_H Half-life (hr)
2.0 540
6.0 410
9.0 180
I/ Konrad, J. G., and G. Chesters, "Degradation in Soils of Ciodrin and
Organophosphorus Insecticide." J. Agr. Food Chem.. 17(2):226-230
(March-April 1969).
23
-------
The data of Konrad and Chesters (1969) shows a linear relationship between
PR's indT ? Cr°<;0xyPh°s remaining and-time progression for each of the
pH s indicating that hydrolysis follows first-order kinetics.
Porter (1967) reported the following half-lives in water at 38°C:
EM. Half-life (hr)
1
9
87
35
Konrad and Chesters (1969) listed the hydrolysis products for
degradation in soil or water. In their study, no ^C-labeled methanol
T ^et^6d am°ng the soil-free hydrolysis products. Thus, cleavage
£5. * P:°~CH3 bonds d°es not appear to be environmentally significant.
This finding is supported by a study (Chamberlain, 1964)!/ using 32P-
crotoxyphos in which dimethyl phosphate was detected as the major metabo-
lite. These products and the apparent pathway to them are shown in the
following diagram:
0
(CII30) 2POC=CHC02CHC6H5 hydrolysis^
CH-.
in soil or
water
0
(CH30)2POC=CHC02H
CH3
3-(raethoxyphos-
phinyloxy)-
crotonic acid
(CH30)2POH + HOC=CHC02H
dimethyl-
phosphoric
acid
CH3
1-phenyl-
ethanol
cis-hydroxvcrotonic
acid
If Chamberlain, W. F., "The Metabolism of 32p_Labeled Shell SD-4294 in
a Lactating Ewe," J. Econ. Entomol., 57:119 (1964).
24
-------
Porter (1967) states that hydrolysis produces all of the products
which can be formed from the cleavage of the P-O-C bonds and the C-O-C
bonds of the crotoxyphos molecule. Under alkaline conditions, Porter
states that dimethyl phosphate and 1-phenylethyl acetoacetates predominate:
0
n
(CH30)2POC=9HC02CHC6H5
CH3 CH3
crotoxyphos
Alkaline
Hydrolysis
0
^ (CH30)2PONa
dimethyl
phosphate
CH3CCH2C02CHC6H5
CH3
1-phenylethyl
acetoacetate
The hyrdolysis of crotoxyphos in aqueous solution is fairly rapid.
However, Konrad and Chesters (1969) observed that in soil systems, at
pH values near neutrality, the rates of degradation are approximately
two orders of magnitude greater than in soil-free, aqueous systems at
pH 6.0. (The degradation of crotoxyphos in soils is discussed in the
Fate and Significance Section of this report.)
Other Chemical Reactions - Porter (1967) stated that crotoxyphos will
undergo the following chemical reactions:
1. Sodium iodide in acetone solution fairly selectively cleaves
the P-0-methyl bonds to form the desmethyl derivative:
crotoxyphos
(1) Nal, acetone
(2) H20
2CH3I + (HO)2POCHCH2C02CHC6H5
CH,
OL,
2. The double bond is reactive and will easily add bromine or
hydrogen:
crotoxyphos
L — ^-*
9
CH,
CH.
crotoxyphos
(CH30)2POCBrCHBrC02CHC6H5
CH3 CH3
3. The benzene ring can be nitrated without destroying the molecule
using concentrated nitric acid-concentrated sulfuric acid mixture:
crotoxyphos
HN03
H2S04
(CH30) 2POC=CHC02CHY Q
CH
25
-------
Westlake et al. (1969) suggested a method of analysis for crotoxyphos
by acid hydrolysis followed by oxidation to acetophenone, which can then be
determined by oscillopolarography. The chemical reactions are as follows:
crotoxyphos - 2£i^ - ^ HOCHC£Hc oxidation> CHoCOCfiHs
hydrolysis L,
CHo
1-phenylethanol acetophenone
Occurrence of Crotoxyphos in Food and Feed Commodities
The Food and Drug Administration (FDA), Department of Health, Education
and Welfare", monitors pesticide residues in the nation's food supply. Much
of these data are published and the literature is voluminous. However, a
search of the published data has revealed that crotoxyphos has not been
reported as a significant residue in any food class.
From conferences with FDA officials, it was learned that the multi-residue
analytical system used by the FDA laboratories (in Kansas City) would not
detect crotoxyphos. Crotoxyphos is one of the relatively volatile pesticides
(an "early eluter" in the gas chromatographic analysis) and special techniques
are required for its detection. Ordinarily, if the FDA does not- expect to
find a particular pesticide, they do not perform the specific methodology
necessary to detect it. Thus, the absence of crotoxyphos in the residue data
does not mean that it is not present.
Acceptable Daily Intake
The acceptable daily intake (ADI) is defined as the daily intake which,
during an entire lifetime, appears to be without appreciable risk on the basis
of all known facts at the time of evaluation (Lu, 1973) .I/ It is expressed in
milligrams of the chemical per kilogram of body weight (mg/kg) .
The Food and Agricultural Organization/World Health Organization (FAO/WHO)
establishes ADI levels. An ADI for crotoxyphos, which has only noncrop uses,
has not yet been determined by FAO/WHO.
Tolerances
Tolerances for crotoxyphos, established under the purview of the Food,
Drug, and Cosmetic Act, as amended, are cited in the Code of Federal Regula-
tions, specifically for "negligible residues" of dimethyl phosphate of a-methyl-
benzyl 3-hydroxy-cis-crotonate in meat, fat and meat by-products of cattle,
goats, hogs, and sheep and in milk at 0.02 ppm.— '
I/ Lu, F. C., "Toxicological Evaluation of Food Additives and Pesticide
Residues and Their 'Acceptable Daily Intakes' for Man: The Role of WHO,
in Conjunction with FAO," Residue Rev., 45:81-93 (1973).
2/ Code of Federal Regulations, Title 40, Chapter 1, Subchapter E, Subpart C,
Section 180. 280.
26
-------
References
Association of Official Analytical Chemists, Official Methods of Analysis
of the Association of Official Analytical Chemists, llth ed., Washington,
D.C. (1970).
Beckman, H., and D. Garber, "Recovery of 65 Organophosphorus Pesticides
from Florisil with a New Solvent Elution System," J. Assoc. Off. Anal.
Chem., 52(2):286-293 (1969).
Beynon, K. I., D. H. Hutson, and A. N. Wright, "The Metabolism and Degrada-
tion of Vinyl Phosphate Insecticides," Residue Rev., 47:55-142 (1973).
Bowman, M..C., and M. Beroza, "GLC Retention Times of Pesticides and
Metabolites Containing Phosphorus and Sulfur on Four Thermally Stable
Columns." J. Assoc. Off. Anal. Chem.. 53(3):499-508 (1970).
Caswell, R. L., D. E. Johnson, and C. Fleck, Acceptable Common Names and
Chemical Names for the Ingredient Statement on Pesticide Labels (2nd ed.),
Environmental Protection Agency, Washington, D.C. (June 1972).
Chamberlain, W. F., "The Metabolism of 32P-Labeled Shell SD-4294 in a
Lactating Ewe," J. Econ. Entomol., 57:119 (1964).
Code of Federal Regulations. Title 40, Chapter'1, Subchapter E, Subpart C,
Section 180. 280.
Czech, F. P., "Analysis of Insecticides in Aqueous Emulsions Used in
Livestock Dips and Sprays: General Infrared Method," J. Assoc. Off.
Agr. Chem.. 47(5):829-837 (1964).
Fukoto, T. R., and J. J. Sims, "Metabolism of Insecticides and Fungicides,"
In: R. White Stevens (ed.) Pesticides in the Environment. Marcel Dekker,
Inc., New York (1971).
Konrad, J. G., and G. Chesters, "Degradation in Soils of Ciodrin and
Organophosphorus Insecticide." J. Agr. Food Chem.. 17(2):226-230 (March-
April 1969).
•
Lu, F. C., "Toxicological Evaluation of Food Additives and Pesticide
Residues and Their 'Acceptable Daily Intakes' for Man: The Role of
WHO, in Conjunction with FAQ," Residue Rev.. 45:81-93 (1973).
Martin, H., Pesticide Manual. British Crop Protection Council, 2nd ed.
(1971).
Melnikov, N. N., Chemistry of Pesticides. Vol. 36 of Residue Rev.. Springer-
Verlag, New York (1971).
Merck Index. The. P. €. Strecher (ed.), 8th ed., Merck and Co., Rahway,
N.J., (1968).
27
-------
Metcalf, R. L. , "Chemistry and Biology of Pesticides," In: R. White Stevens
(ed.): Pesticides in the Environment, Marcel Dekker, Inc., New York (1971)
Oehler, D. D., and H. V. Claborn, "Determination of Crotoxyphos in Milk and
in the Body Tissues of Cattle and Pigs," J. Assoc. Off. Anal. Chem.,
53(5) H045-1047 (1970).
Porter, P. E., "CiodrinvS) Insecticide," Analytical Methods for Pesticides,
Plant Growth Regulators, and Food Additives, Vol. V, Additional Principles
and Methods of Analysis, Chap. 11, Academic Press, Inc., New York (1967).
Shell Chemical Company, "Summary of Basic Data for Technical Ciodrin^/
Insecticide," Technical Bulletin, San Ramon, Calif. (1962).
Shell Development Company, Agricultural Research Division, Analytical
Method MMS-38/64 (July 1964).
Shell Development Company, Biological Sciences Research Center, Modesto,
Calif., MMS-R-268-1 (April 1971).
Shell Development Company, Biological Sciences Research Center, Modesto,
Calif., MMS-C-298-1 (November 1971).
Tieman, C. H., and A. R. Stiles, "Preparation of Vinyl Esters of Phosphorus
Acids Useful as Insecticides," U.S. Patent No. 3,068,268 (to Shell Oil
Company, 11 December 1962).
U.S. Department of Health, Education and Welfare, Food and Drug Administra-
tion, Pesticide Analytical Manual, 2 vols. (1971).
Watts, R. R., and R. W. Storherr, "Gas Chromatography of Organophosphorus
Pesticides; Retention and Response Data on Three Columns," J. Assoc. Off.
Anal. Chem., 52(3):513-521 (1969).
Westlake, A., F. E. Hearth, F. A. Gunther, and W. E. Westlake, "Determina-
tion of Ciodrin from Fortified Animal Tissues by Oscillopolarography of
Its Conversion Product Acetophenone," J. Agr. Food Chem., 17(6):1160-1163
(1969).
Westlake, A., F. A. Gunther, and W. E. Westlake, "Conversion of the
Insecticide Ciodrin to Acetophenone for Microdetermination," J. Agr. Food
Chem.. 17(6):1157-1159 (1969).
Whetstone, R., and D. Barman, "Insecticidally Active Esters of Phosphorus
Acids and Preparation of the Same," U.S. Patent No. 2,956,073 (to Shell
Oil Company, 11 October 1960).
28
-------
Whetstone, R., and D. Harman, "Organo-Phosphorus Insecticide" U.S. Patent
No. 3,116,201 (to Shell Oil Company, 31 December 1963).
Whetstone, R., and A. R. Stiles, "Arylphosphate Compounds," U.S. Patent No.
2,982,686 (to Shell Oil Company, 2 May 1961).
Zweig, G., and J. Sherma, Analytical Methods for Pesticides and Plant
Growth Regulators, Vol. VI; Gas Chromatographic Analysis, Academic Press,
Inc., New York (1972).
29
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PART II. INITIAL SCIENTIFIC REVIEW
SUBPART B. PHARMACOLOGY AND TOXICOLOGY
CONTENTS
Page
Acute, Subacute and Chronic Toxicity 32
Toxicity to Laboratory Animals 32
Acute Oral Toxicity - Rats 32
Acute Toxicity - Rats (Routes Other Than Oral) 32
Demyelination 36
Acute Oral Toxicity - Mice 36
Acute Oral Toxicity - Chicks 36
Subacute Oral Toxicity - Chickens 36
Subacute Oral Toxicity - Dogs 36
Acute Toxicity - Cats 36
Acute Toxicity - Rabbits 41
Toxicity to Domestic Animals 41
Metabolism 47
Absorption 47
Distribution 47
Excretion 47
Biodegradation 51
Tissue Residues ' 52
Effects on Reproduction 53
Mutagenic Effects 53
Teratogenic Effects 53
Symptomology 53
Antidote 54
Accidents 54
References 55
31
-------
This section reviews pharmacological and toxicological data on
crotoxyphos. The acute, subacute and chronic toxicity data for a
number of species by various routes of administration is discussed.
Data is presented on metabolism, effects on reproduction, and mutagenic
and oncogenic effects. Data is also included on human exposure to
crotoxyphos. This section summarizes rather than interprets scientific
data reviewed.
Acute, Subacute and Chronic Toxicity
Toxicity .to Laboratory Animals -
Acute oral toxicity - rats - The results of a number of tests for
the acute oral toxicity of crotoxyphos to rats are shown in Table 1.
There is a large variation in the acute toxicity as reported by several
investigators for the technical compound. The acute oral 1050 ranges
from 38.4 (Vorobieva and Lapchenko, 1973)!/ to 125 mg/kg (Simelskii, 1970)
The variation in acute LD5Q values is evidently due to differences in
experimental techniques such as choice of vehicle and whether animals
are fasted. As shown in Table 1, female rats appear to be slightly
more susceptible to this compound than male rats (Gaines, 1969).J/
Symptoms of toxicity of rats exposed to crotoxyphos are due to
cholinesterase inhibition. The symptoms include: excessive salivation,
tremors, convulsions, lacrimation and diarrhea (Shellenberger and Newell,
1961) A'
Acute toxicity - rats (routes other than oral) - The toxicity of
crotoxyphos for rats by routes of exposure other than oral is shown in
Table 2. The dermal LD^Q indicates that the compound is absorbed fairly
well from the skin. A dermal LD50 of 202 mg/kg for the female rat is
reported by both Ben-Dyke, et al. (1970)A/ and Gaines (1969).
I/ Vorobieva, N. M., and V. S. Lapchenko, "Toxicity and Hygienic
Standardization of Ciodrin Pesticide," Gigiyena I Santariya, Moscow,
38(6):30-33 (1973).
2_/ Simelskii, M. A., "The Toxicity of Ciodrin for Warm-blooded Animals
and Arthropods," Tr. Vses. Nauchno-Issled. Inst. Vet. Sanit. (1970).
3/ Gaines, Thomas B., "Acute Toxicity of Pesticides," Toxicol. Appl.
Pharmacol., 14(3):515-534 (1969).
4/ Shellenberger and Newell, Stanford Research Institute, EPA Pesticide
~ Petition No. 9F0770 (1961).
5/ Ben-Dyke, R., D. M. Sanderson, and D. Noakes, "Acute Toxicity Data for
~ Pesticides," World Review of Pest Control, 9(3):119-127 (1970).
32
-------
Table 1. ACUTE ORAL TOXICITY OF CROTOXYPHOS TO RATS
Formulation
Technical
Technical
Measurement
LD50
LD50
Results
(mg/kg)
Male Female
74-125
110 74
References
n
w
Technical*
LD
5Q
(95-128)*** (65-84)
125
(100-147)
/
u>
u>
Technical
21-112
Technical
LD50 (ml/kg)
0.0584
(0.0476-0.0716)
£./
Technical
Technical*
Technical*
Wettable powder
25°/S
LD1 55
Lowest lethal 100
dose
LD
50
125
38.4*7.8
42
63
288^
236-356
f/
y
y
c/
-------
Table 1 (Continued)
Formulation
Emulsible concen-
trate 3.2
(Ib/gal)
Measurement
Results
(mg/kg)
Male Female
LD
50
0.213
(0.195-0.234)
21.3-4.3
References
c/
d/
U)
4S
*
**
***
£/
I/
£/
f/
&/
Dissolved or suspended in peanut oil.
Dissolved in water.
LDjQ formulation 1 kg = 72 mg crotoxyphos per kilogram (59-89)
LD5Q formulation 1 kg = 81 mg crotoxyphos per kilogram (74-89).
Data in parentheses represent 95% confidence limits.
Ben-Dyke, et al., op. cit. (1970).
Gaines, op. cit. (1969).
Shellenberger and Newell, op. cit. (1961).
Witherup and Schlecht, Kettering Laboratory, EPA Pesticide Petition 9F0770,
Vol. 1. (1964).
Doyle and Elsea, Hilltop Research, EPA Pesticide Petition 9F0770 (1966).
Simelskii, op. cit. (1970).
Vorobieva and Lapchenko, op. cit. (1973).
-------
Table 2. ACUTE TOXICITY OF CROTOXYPHOS FOR RATS VIA ROUTES OTHER THAN ORAL
Results
Measurement Male (ing/kg) Female Reference
Subcutaneous LDlO 106
(62.9-126.1)* 5/
Subcutaneous LD5Q 148.8
(124.5-179.4) £/
Subcutaneous LDgo 208.9
(174.8-360.1) a/
Dermal LD5Q 202 b/
u>
01 Dermal LD. 200 130 c/
I ~~
Lowest dose
to kill 300 150 c/
Dermal LDso 375 202
(323-435) (177-230) £/
* Data in parentheses represent 95% confidence limits.
a/ Natoff, I. L., and B. Reiff, "Quantitative Studies of the Effect of
Antagonists on the Acute Toxicity of Organophosphates in Rats,"
Brit. J. Pharmac.. 40:124-134 (1970).
b_/ Ben-Dyke, et al., op. cit. (1970).
£/ Gaines, op. cit. (1969).
-------
Crotoxyphos is readily absorbed from the lungs. The inhalation toxicity
of both the technical and 3.2 Ib/gal formulation is such that both are in the
highly toxic category (defined as LC$Q < 2 mg/1 for a 1 hr exposure).-'
The subacute oral toxicity to rats is summarized in Tables 4 & 5.
Feeding crotoxyphos in the diet of rats for 10 months at 0.01 mg/kg
caused no adverse effects. Higher doses caused inhibition of cholines-
terase activity, increase in vitamin C levels in liver and kidney, and
reduced rate of hippuric acid synthesis (Vorobieva and Lapchenko, 1973).
Demyelination - Crotoxyphos does not induce demyelination of peripheral
nerves of chicken (Witherup and Ushry, 1965).
Acute oral toxicity - mice - A summary of the acute oral toxicity of
crotoxyphos to mice is shown in Table 6. When formulated as a wettable
powder, crotoxyphos remains as toxic as its technical form. (Shellenberger
and Newell, 1961).
Acute oral toxicity - chicks - A summary of the acute oral toxicity
of crotoxyphos to chicks is given in Table 7. A U>50 of 111 mg/kg is
reported by Sherman et al. (1965)^./ and an LD5Q of 147 mg/kg is reported
by Witherup and Ushry (1965).
Subacute oral toxicity - chichens - A 1-week feeding study to chickens
at levels of 50, 100, 200, 400 and 800 ppm in the diet showed that 800 ppm
caused a 50% inhibition of plasma cholinesterase (Sherman et al., 1965).
This data is summarized in Table 8.
Subacute oral toxicity - dogs - The subacute oral toxicity of
crotoxyphos to dogs is summarized in-Table 9. Feeding crotoxyphos in
the diet of dogs for 12 weeks at levels of 5, 15, and 45 ppm caused no
effect on growth or organ weights at any level of exposure. However,
15 and 45 ppm caused a depression of plasma and RBC cholinesterase
activity. When 135 ppm were fed for 2 weeks, brain cholinesterase was
not affected. Microscopic examination of tissues at all dose levels in
the 12 week study revealed no pathological changes that could be attributed
to the compound (Shellenberger and Newell, 1961). The cholinesterase
no-effect level in dogs appears to be 5 ppm.
Acute toxicity - cats - The acute oral LDso of crotoxyphos to cats is
802 +9.02 mg/kg (Vorobieva and Lapchenko, 1973).
I/ Witherup and Ushry, Kettering Laboratory, EPA Pesticide Petition
No. 9F0770 (1965).
2/ Sherman, M., E. Ross, and M. T. Y. Chang, "Acute and Subacute Toxicity
of Several Insecticides to Chicks," Toxicol. Appl. Pharmacol., 7:
606-608 (1965).
36
-------
Table 3. ACUTE INHALATION TOXICITY OF CROTOXYPHOS TO RATS
Method of
exposure
Dynamic Flow
(Technical
Material)
Dynamic Flow
3.2 Ib/gal
(38.2%)
Exposure
formulation time
45 min
64 min
120 min
240 min
60 min
60 min
140 min
Percent
mortality
100
40
60
0
70
0
0
Chamber concen-<
tration mg/jfc
1.67
0.67
0.61
0.34
0.94
0.78 *
0.42 *
Source: Witherup and Ushry, op. cit. (1965).
* Active ingredient = formulation concentrations approximately 2.04
and 1.10 mg/1.
-------
Table A. SUBACUTE ORAL TOXICITY TEST IN RATS
Concentration of
CiodrinVy in feed (ppm)
0, 100, 300, 900
Duration
of test
12 weeks
0. 7, 20, and 60
12 weeks
0, 10, 30, 100, 250,
750, 2000, 4000, 6000
2 weeks
Comments
Growth of female rats
significantly less than
controls at 900 ppm.
Hematology of males and
females not effected at
any level.
Slight inhibitory effect on
whole blood cholinesterase
at 20 ppm. 600 caused
marked influence.
No effect on rat brain
cholinesterase at 250 ppm;
marked depression at 750 ppm.
In males, no blood cholin-
esterase inhibition occurred
with 10 ppm, while in females
this level caused inhibition.
Microscopic examination of
tissues of animals exposed to
all dose levels revealed no
pathological changes attribu-
ted to the compound.
Source: Shellenberger and Newell, op. cit. (1961).
38
-------
Table 5. SUBACUTE TOXICITY OF CROTOXYPHOS TO RATS
Daily Dose Duration Percent
ing/kg of Test Mortality
0.01
0.05 and
0.25
10 months
0
10 months
0.77, 1.92
and 3.84 10 months 0
Comments
No effect on cholinesterase
activity, no gross signs of
toxicity.
Reduced eosinophilic cell count
in hypophysis and adrenal cortex.
Increased Vit C content in
adrenal glands and elevated blood
sugar levels. No gross signs of
toxicity.
Inhibition of cholinesterase
activity, increased Vit C levels
in liver and kidney. Reduced
rate of hippuric acid synthesis.
Source: Vorobieva and Lapchenko, op. cit. (1973).
39
-------
Table 6. ACUTE ORAL TOXICITY OF CROTOXYPHOS TO MICE
LD50 of
Formulation ^50 °^ crotoxyphos
tested formulation equivalent Reference
39.8 — £/
+10.6 mg/kg
3.2 Ib/gal 0.16 ml/kg 61 mg/kg b/
(0.14-0.187) (53-71)
25% Wettable 288 rag/kg 72 mg/kg b/
Powder (232-256) (58-89)
Technical 83% -- 89 mg/kg b/
(76-103)'
a/ Vorobieva and Lapchenko, op. cit. (1973).
b_/ Shellenberger and Newell, op. c'it. (1961).
40
-------
Acute toxicity - rabbits - The dermal toxicity of crotoxyphos to rabbits
is summarized in Table 10. Crotoxyphos appears to be fairly well absorbed
from the skin of the animal. There are wide variations in the acute dermal
toxicity as determined by several investigators. This is most likely due to
differences in experimental techniques.
Toxicity to Domestic Animals - Numerous studies have been undertaken to deter-
mine the safety of crotoxyphos to a variety of domestic animals. Weidenbach
and Younger (1962)—' dipped sheep and goats in 1% emulsion of crotoxyphos and
sprayed swine and young dairy calves with 0.5 and 2% emulsions to run-off.
The only signs of toxicity were diarrhea and muscular weakness to some dairy
calves when sprayed with the 2% emulsion. These findings are summarized in
Table 11.
The effects of crotoxyphos applied to Brahman calves, and Brahman and cross-
bred steers were also studied by Greer, et al. (1973).—' Animal toxicosis
was determined by clinical symptoms such as cholinesterase inhibition, dyspnea,
constriction of pupils, diarrhea, profuse salivation, inability to stand, and
clonic convulsion.
The crotoxyphos formulations used were an emulsifiable concentrate (132
g/llter) and a 3% dusting powder.
The experimental groups of Brahman calves for 21-day tests were (1) con-
trols, (2) a 3% dust group, (3) a 0.5% spray group and (4) a 1% spray group.
The dust was applied at 57 g/head/day. The sprays were applied weekly at 946
ml/head.
The Brahman calves treated with 946 ml of 1% spray per head exhibited
inhibition in whole blood and red cell cholinesterase. Two of four calves
exhibited severe toxicosis and one developed skin lesions.
Calves treated with 946 ml of 0.5% spray or 57 g of 3% dust exhibited
cholinesterase inhibition but other signs of toxicosis were not observed.
Whole blood and red cell cholinesterase of Brahman and crossbred steers
were inhibited when treated with 1.9 liter of 0.5% crotoxyphos spray per head
at weekly intervals for 11 weeks. Brahman steers exhibited a greater reduc-
tion than crossbred steers.
In another acute dermal study, it was shown that Brahman cattle were
more sensitive to crotoxyphos than European-crossbreed when the dermal toxic-
ities were compared (Palmer and Danz, 1964) .-5.' This is shown in Table 12.
I/ Weidenbach, Carl P., and R. L. Younger, "The Toxicity of Dimethyl 2-(alpha-
methylbenzyloxycarbonyl)-l-methylvinyl phosphate (Shell Compound 4294)
to Livestock" J. Econ. Entomol., 55(5):793 (1962).
2/ Greer, N. I., M. J. Janes, and D. W. Beardsley, "Toxicity of Crotoxyphos
Insecticide to Brahman and Crossbred Yearling Steers," Fla. Ent. 56:
243-250 (1973).
_3/ Palmer, J. S., and J. W. Danz, "Tolerance of Brahman Cattle of Organic
Phosphorus Insecticides," J. Amer. Vet. Med. Assoc., 1944(2):143-145
(1964).
41
-------
Table 7. ACUTE ORAL TOXICITY OF CROTOXYPHOS TO CHICKS
Formulation
Technical
Technical
Technical
Measurement
LD
50
LD50
LD
50
Results
(mg/kg)
Male Female
111
(101-122)*
147 + 8
147
References
c/
* Data in parentheses represent 95% confidence limits.
£/ Sherman et al., op- cit. (1965).
b_/ Witherup and Schlect, op. cit. (1964).
£/ Witherup and Ushry, pp. cit. (1965).
Table 8. SUBACUTE ORAL TOXICITY TEST IN WHITE LEGHORN COCKERELS
Ciodrin in
feed-ppra
50
100
200
400
800
Duration
of test
1 week
1 week
1 week
1 week
1 week
Percent
mortality
0
0
0
0
0
Comments
The concentration of
Ciodrin in the feed
which resulted in
approximately 50%
inhibition of the
cholinesterase of
blood plasma at the
end of 1 week is
800 ppm.
Source: Sherman et al., op. cit. (1965).
42
-------
Table 9. SUBACUTE ORAL TOXICXTY TEST IN DOGS
Concentration of
crotoxyphos in feed
(ppm)
5, 15, and 45
Duration Percent
of test mortality
12 weeks 0
OJ
135
2 weeks
Comaents
No effect on growth or organ
weights. In male dogs
plasma cholinesterase
activity inhibited at 15
and 45 ppm. In females
cholinesterase activity
markedly reduced at 45 .
ppm. RBC cholinesterase
activity of male dogs
slightly effected at 15
ppm and significantly at
45 ppm. In females 5 and
15 ppm exposure did not
inhibit RBC cholinesterase
activity, but inhibition
occurred at 45 ppm. In-
hibition returned to normal
levels after 2-3 weeks.
Brain cholinesterase activity
not affected at 5, 15, and
45 ppm.
Brain cholinesterase activity
not affected. Microscopic
examination of tissues at
all dose levels revealed no
pathological changes attrib-
ted to the compound.
Source: Shellenberger and Newell, op. cit. (1961).
-------
Table 10. ACUTE DERMAL TOXICITY TO RABBITS
Formulation Measurement
Technical
LD
50
Results
(mg/kg)
Male Female
742+102
References
a/
Technical
LD
'50
LD
50
1780(1210-2610):
384
(295-500)
3.2 Ib/gal
LD
50
200
£./
Emulsible con-
centrate
338(152-750)
b/
25% wettable LD5Q > 1,250
powder
* Data in parentheses represent 95% confidence limits.
a/ Witherup and Schlect, Kettering Laboratory, EPA Pesticide Petition
No. 9F0770 (1962).
b/ Shellenberger and Newell, op. cit. (1961).
c/ Palazzolo, R., Industrial Bio-Test Laboratories, EPA Pesticide
Petition No. 9F0770 (1963).
-------
Table 11. ACUTE DERMAL TOXICITY OF CROTOXYPHOS
TO SOME DOMESTIC SPECIES
Animal
species
Young
dairy
calves
Angora
Goats
Sheep
Swine
Emulsion
concentration
0.57,
emulsions
2.0%
emulsion
0.5%
and
1%
0.5%
and
1%
2%
Volume
applied
Thoroughly
wetted with
4 liters of
solution as
a spray.
Thoroughly
wetted by
dipping.
Thoroughly
wetted by
dipping.
Sprayed with
1.25 liters
per head.
Comments
Not affected
by treatment
at 0.5%.
Diarrhea and
muscular weak-
ness in 7 of 11
animals treated
at 2%.
No visible
harmful effects.
No visible
harmful effects.
No visible
harmful effects.
Source: Weidenbach and Younger, op. cit. (1962).
45
-------
Table 12. COMPARATIVE DERMAL TOXICITY TO CATTLE
Animal
Volume
of
Emulsion emulsion
concentration (gal/head)
Comments
Brahman
cross
European 6
0.6%'
Brahman
European
cross
Brahman
European
cross
Brahman
0.67,
1.0%'
1.07,/
1.07.1
1.0%'
1.25-2.0 Absence of gross
signs of toxicity
or cholinesterase
activity depression.
1.25-2.0 No gross signs of
toxicity or cholin-
esterase activity
depression.
1.25-2.0 Cholinesterase activity
depressed 13% of normal.
Moderate gross signs of
toxicity.
1.25-2.0 Gross signs of toxicity
. evident in some animals.
Cholinesterase activity 63%
of normal.
1.25-2.0 Most animals exhibited gross
symptoms of toxicity. Cholines-
terase activity 45% normal.
1.25-2.0 No evidence of gross toxic signs.
Cholinesterase 66% normal.
1.25-2.0 Moderate to severe toxic symp-
toms in majority of animals.
Cholinesterase activity 34% normal,
* Diluted from 3 Ib/gal B.C.
yt Diluted from 25% wettable powder.
± Diluted from 14.47« B.C.
** Diluted from 4 Ib/gal B.C.
Source: Palmer and Danz, op. cit. (1964).
46
-------
In subacute dermal studies, pigs (Palmer and Schlinke, 1971)1-'
yearling cattle (Weidenbach and Younger, 1962), adult cattle (Singh and
Fireoved, 1964)2/ and horses (Knapp et al., 1967)1' have been exposed
to various concentrations of emulsions for varying lengths of time.
Pigs, horses, and adult cattle exhibited cholinesterase depression
during treatment or post-treatment period. This data is summarized in
Tables 12, 13, and 14.
Metabolism
Absorption - Chamberlain (1964)A/ demonstrated that 32P-crotoxyphos given
orally to lactating sheep or dermally to lactating goats was absorbed by
both routes. Ivie et al. (1967)A/ demonstrated that.crotoxyphos inhibited
acetylcholinesterase. Using this as a criterion for absorption, Vorobieva
and Lapchenko (1973) reported that 0.01 mg/kg of crotoxyphos administered
orally on a chronic basis to mice, rats, and cats produced a depression of
liver cholinesterase activity.
Distribution - Chamberlain (1964) found 32p_crotoxyphos ±n sheep blood 6
hr after an oral dose given in capsule form.
Excretion - Chamberlain (1964) reported that the peak urinary excretion of
orally administered 32p_crotoxyphos ifl lactating sheep was 6 hr after
dosing. After 48 hr, 78.7% of the dose was present in the urine and 7.25%
in the feces. Chamberlain (1964) treated lactating goats dermally with
32p-crotoxyphos and recovered 11% of the radioactivity in the urine. The
highest milk concentration was 0.2 ppb. Beynon et al. (1973)JJ/ reported
that cows sprayed with 0.03% crotoxyphos had a maximum milk concentration
of 0.007 ppm. After 2 days, this decreased to 0.001 ppm and was undetectable
thereafter.
JL/ Palmer, J. S.;and J. C. Schlinke, "Toxicologic Effects of Two Crotoxy-
phos Formulations on Pigs," J. Econ. Entomol., 64(3):1971 (1971).
21 Singh and Fireoved, Report on Crotoxyphos, Bio-Toxicological Research
Associated, EPA Pesticide Petition No. 9F0770 (1964).
3/ Knapp, F. W., J. H. Drudge, and Eugene Lyons, "Toxic Effect of Ciodrin
and Dichlorvos Applied Topically to Horses and Their Efficacy Against
Internal Parasites," J. Econ. Entomol.. 60(2):330-332 (April 1967).
4/ Chamberlain, W. F., "The Metabolism of 32p-Labelled Shell SD-4294 in
a Lactating Ewe," J. Econ. Entomol.. 57:119 (1964).
5f Ivie, G. W., L. R. Green, and H. W. Dorough, "The Use of Sodium
Bicarbonate - C14 to Determine Cholinesterase Activity," Bull.
Environ. Contam. Toxicol.. 2(1):34-40 (1967).
6f Beynon, K. I., D. H. Hutson, and A. N. Wright, "The Metabolism and
Degradation of Vinyl Phosphate Insecticides," Residue Rev.,
45:96-101 (1973).
47
-------
Table 13. SUBACUTE DERMAL TOXICITY OF CROTOXYPHOS
TO PIGS AND CATTLE
Animal
Pig
Duration
of
test
3 weeks
Percent
mortality
Pig
3 weeks
0
Yearling
cattle
16 weeks
0
Comments
References
One liter of a 17» emulsion
was applied dermally to
pigs for 3 weeks. Signs
of toxicosis were seen
after first spray appli-
cation. There were area
of skin erythema accompanied
by squealing, salivating, and
rubbing. Cholinesterase
markedly depressed in one
animal on second day of the
first exposure.
a/
0.5 and 1 liters of a 17.
emulsion of a 240 g/liter
EC and 1 liter 120 g/liter
formulation were applied
dermally at weekly inter-
vals for 3 weeks to 3 groups
of animals to evaluate influence
on cholinesterase activity.
There were neither overt signs
of toxicosis nor dermatosis in
any group. However cholinesterase
inhibition was exhibited by all
groups 1 day after treatment and
continuing throughout the experi-
ment.
1.5 gal. of a 0.5% or 2%
emulsion were sprayed to
each head of cattle with-
out visible harmful effects.
48
-------
Table 13 (Continued)
Animal
Cattle
Duration
of
test
3 days
Percent
mortality
Comments
Whole blood
cholinesterase
activity depressed.
Activity returns to
normal 7-8 weeks
after treatment stopped.
Growth and well being
not affected.
References
c/
a/ Palmer and Schlinke, op. cit. (1971).
b/ Weidenbach, and Younger, op. cit. (1962)
c/ Singh and Fireoved, op. cit. (1964).
49
-------
Table 14. SUBACUTE DERMAL TOXICITY TO HORSES
Animal
Horse
Duration
of
test
12 days
Percent
mortality
Comments
References
1 pt 2% crotoxyphos
EC in water poured on
5 times at 3-day inter-
val (22.3 ing/kg each
treatment) caused
depression of cholines-
terase activity of
plasma for 8 days after
last treatment. No
signs of toxicity
were observed.
a/
Horse
7 days
4 oz of 27, crotoxy-
phos in oil sprayed
daily for 7 days (9
mg/kg) caused inhi-
bition of plasma
cholinesterase activity.
No clinical signs
.of toxicity were observed,
a/
a/ Knapp et al., op. cit. (1967).
50
-------
Biodegradation - Oehler and Claborn (1970)1.' attempted to recover crotoxy-
phos from several cattle and pig tissures jin vitro. Recovery was 80 to 95%
from all tissues tested except blood. Recovery from beef blood was 82%
immediately after mixing but only 25% after standing for 1 hr. In pig
blood, these figures were 79 and 42%, respectively.
Chamberlain (1964) studied the metabolism of 32P-crotoxyphos in
lactating sheep. The major urinary metabolite was dimethyIphosphoric
acid (84% in 6 hr). After 3 hr 10% of the urinary metabolites was 3-
(dimethoxy phosphinyloxy) crotonic acid. Seven other minor metabolites
were found but not identified. Sheep may respond differentially to the
01- and 3-isomers of crotoxyphos since only P-crotoxyphos could be found
in milk 5 hr after treatment. The peak radioactivity in the blood occurred
6 hr after treatment. The chloroform-exactable radioactivity in the 6 hr
blood samples contained 66% cv-isomers and 31% P-isomers.
Chamberlain (1964) found that 80 to 91% of 32P-crotoxyphos excreted
in the urine of lactating goats after dermal treatment was in the form
of dimethyIphosphoric acid.
Beynon et al. (1973) reported that the carboxylic acid that resulted
from the de-esterification of crotoxyphos was also a weak cholinesterase
inhibitor but of minor importance. They reported that the metabolic
pathways of crotoxyphos in mammals and soil were essentially the same.
I/ Oehler, D. D., and H. V. Claborn, "Determination of Crotoxyphos in
Milk and in Body Tissues of Cattle and Pigs," J. Assoc. Official
Agr. Chem., 53:1045 (1970).
51
-------
They proposed the following three pathways for the metabolic
degradation of rrotoxyphos:
CH3Ov f
CH30 0-C=C-C
CH3 OH
/ \ H '/
CH30 0-C=C-C CH3 r^^
CH3 X0-C
H \L^
crotoxyphos
acetoacetic
acid
-> CH3-0 OH
0 0 CH3 / y
+ CH3-C-CH2-C-0-C^/ \
f-phenylethyl-
acetoacetate
Pathway B is probably the main pathway in mammals, while A produces the
minor acid metabolite which is the weak cholinesterase inhibitor.
32
Tissue Residues - The relatively rapid excretion of P-crotoxyphos
by sheep (Chamberlain, 1964), goats (Chamberlain, 1964) and cows
(Benynon et al., 1973) and its disappearance from milk after a few
days suggests little or no accumulation in animal tissues. However,
Vorobieva and Lapchenko (1973) found that chronic administration of
crotoxyphos at 0.01 mg/kg/day in rats, mice, and cats depressed
liver cholinesterase, increased liver and kidney vitamin C and
decreased hipuric acid synthesis.
52
-------
Effects on Reproduction
Macklin and Ribelin (1971)—' showed that feeding crotoxyphos to
pregnant cattle failed to produce abortions.
Mutagenic Effects
2 /
Dean (1972)—' showed that crotoxyphos failed to induce a reverse
mutation in Escherichia coli WP2 on solid medium.
Teratogenic Effects
Crotoxyphos did not cause any teratogenic effects in embryos when
hen's eggs were injected on day 4 of incubation (Roger et al., 1968).!/ or
when eggs were injected on day 5 of incubation (Flockhart and Casida,
1972) JS
Svmptomology - Acute intoxication of animals by crotoxyphos is indicated
by cholinesterase inhibition. Other symptoms are of rapid onset at toxic
doses and appear within 30 min when crotoxyphos is administered orally to
rats. These symptoms include tremors*, clonic convulsions, lacrimation,
salivation and diarrhea (Shellenbergei; and Newell, 1971; Doyle and Elsea,
1965). Within 2-1/2 hr following administration, most of the signs of
acute intoxication in surviving animals Vave subsided. Death usually
occurs within 1 hr after a lethal dose (Paiazzolo, 1963).
I/ Macklin, A. W., and W. E. Ribelin, "Relation of Pesticides to Abortion
in Dairy Cattle," J. Amer. Vet. Med. Assoc., 159(12):1743-48 (1971).
2J Dean, B.J., "The Mutagenic Effects of Organophosphorus Pesticides on
Micro-organisms." Arch. Toxicol., 30:67-74 (1972).
3j Roger, Jean-Claude, G. David Upshall, and J.E. Casida, "Structure-
Activity and Metabolism Studies on Organophosphate Teratogens and
Their Alleviating Agents in Developing Hen Eggs with Special
Emphasis on Bidrin." Biochem. Pharmacol., 18:373-392 (1968).
4/ Flockhart, Jan R., and J.E. Casida, "Relationship of the Acylation of
Membrane Esterases and Protein to the Teratogenic Action of
Organophosphorus Insecticides and Eserin in Developing Hen Eggs,"
Biochem. Pharmacol., 21:2591-2603 (1972).
53
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Signs of toxicity in mallard ducks are similar to those seen in rats.
Ducks exhibit leg weakness, ataxia, wings crossed high over back, and
opisthotonos. Signs appear about 1 hr post-treatment and persist in most
survivors for only a few hours. Death occurs approximately 1 hr after treat-
ment (Tucker, 1968) .i/
Antidote - In rats atropine alone or in combination with N-methylpyridine-
2-aldoxime methane-sulphonate (P25) or (bis-(4 hydroxyiminomethyl pyridinium-
1-methyl) ether dichloride (obidoxime) is antidotal. (Natoff and Reiff,
1970) .
Accidents
Crotoxyphos has not been associated with accidental exposure to man
or the environment to any significant degree. Preliminary data from the
EPA Pesticide Episode Review System (PERS) reported in 1973 that
crotoxyphos was not cited in episodes involving humans, animals, plants
and area contamination. The computerized PERS data base, which generally
includes data for 1972 through early 1974, lists a total of three episodes
involving crotoxyphos. One of these episodes involved potential human
exposures to three pesticides (including crotoxyphos); the other two were
associated with warehouses in flooded areas.
I/ Tucker, R., "Ciodrin," Internal Report Series in Pharmacology, Denver
Wildlife Research Center, Division of Environmental Research, (Nov. 15,
1968).
54
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References
Ben-Dyke, R., D. M. Sanderson, and D. Noakes, "Acute Toxicity Data for
Pesticides," World Review of Pest Control. 9(3):119-127 (1970).
Beynon, K. I., D. H. Hutson, and A. N. Wright, "The Metabolism and
Degradation of Vinyl Phosphate Insecticides," Residue Rev.,
47:96-101 (1973).
Chamberlain, W. F., "The Metabolism of 32P Labelled Shell SD-4294 in a
Lactating Ewe," J. Econ. Entomol.. 57:119 (1964).
Dean, B. J., "The Mutagenic Effects of Organophosphorus Pesticides on
Micro-Organisms," Arch. Toxicol.. 30:67-74 (1972).
Doyle and Elsea, Hilltop Research, EPA Pesticide Petition No. 9F0770
(1966).
Flockhart, Jan R., and J. E. Casida, "Relationship of the Acylation of
Membrane Esterases and Protein to the Teratogenic Action of
Organophosphorus Insecticides and Eserine in Developing Hen Eggs,"
Biochem. Pharmacol.. 21:2591-2603 (1972).
Gaines, Thomas B., "Acute Toxicity of Pesticides," Toxicol. Appl.
Pharmacol., 14(3):515-534 (1969).
Greer, N. I., M. J. Janes, and D. W. Beardsley, "Toxicity of Crotoxyphos
Insecticide to Brahman and Crossbred Yearling Steers," Fla. Ent., 56:243-250
(1973).
Ivie, G. W., L. R. Green, and H. W. Dorough, "The Use of Sodium Bicarbonate -
C14 to Determine Cholinesterase Activity," Bull. Environ. Contain.
Toxicol.. 2(1):34-40 (1967).
Knapp, F. W., J. H. Drudge, and Eugene Lyons, "Toxic Effect of Ciodrin
and Dichorvos Applied Topically to Horses and Their Efficacy Against
Internal Parasites," J. Econ. Entomol., 60(2):330-332 (Aprfl 1967).
Macklin, A. W., and W. E. Ribelin, "Relation of Pesticides to Abortion in
Dairy Cattle," J. Amer. Vet. Med. Assoc.. 159:1743-48.
Natoff, I. L.,-and B. Reiff, "Quantitative Studies of the Effect of
Antagonists on the Acute Toxicity of Organophosphates in Rats,"
Brit. J. Pharmac.. 40:124-134 (1970).
•
Oehler, D. D., and H. V. Claborn, "Determination of Crotoxyphos in Milk
and in Body Tissues of Cattle and Pigs," J. Assoc. Official Agr. Chetn..
53:1045 (1970).
55
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Palmer, J. S., and J. W. Danz, "Tolerance of Brahman Cattle .of Organic
Phosphorus Insecticides," J. Amer. Vet. Med. Assoc.. 144(2):145
(1964). ~
Palmer, J. S.,and J. C. Schlinke, "Toxicologic Effects of Two Crotoxyphos
Formulations on Pigs," J. Econ. Entomol.. 64(3):1971 (1971).
Palazzolo, R., Industrial Bio-Test Laboratories, EPA Petition No. 9F0770
(1963).
Roger, Jean-Claude, G. David Upshall, and J. E. Casida, "Structure-
Activity and Metabolism Studies on Organophosphate Teratogens and
Their Alleviating Agents in Developing Hen Eggs With Special Emphasis
on Bidrin," Biochem. Pharmacol.. 18:373-392 (1968).
Sherman, M., E. Ross, and M. T. Y. Chang, "Acute and Subacute Toxicity of
Several Insecticides to Chicks," Toxicol. Appl. Pharmacol.. 7:606-608
(1965).
Shellenberger and Newell, Stanford Research Institute, EPA Pesticide
Petition No. 9F0770 (1961).
Simelskii, M. A., "The Toxicity of Ciodrin for Warmblooded Animals and
Arthropods," TR Vses. Nauchno-Issled. Inst. Vet. Sanit. (1970).
Singh and Fireoved, Bio-Toxicological Research Associates, EPA Pesticide
Petition No. 9F0770 (1964).
Tucker, R., "Ciodrin," Internal Report Series in Pharmacology, Denver
Wildlife Research Center, Division of Environmental Research,
(Nov. 15, 1968).
Vorobieva, N. M., and V. S. Lapchenko, "Toxicity and Hygienic Standardization
of Ciodrin Pesticide," Gigiyena I Santariya, Moscow, 38(6):30-33 (1973).
Weidenbach, Carl P., and R. L. Younger, "The Toxicity of Dimethyl 2-
(alpha-methylbenzyloxycarbonyl)-l-methylvinyl phosphate (Shell Compound
4294) to Livestock." J. Econ. Entomol., 55(5):793 (1962).
Witherup and Schlecht, Kettering Laboratory, EPA Pesticide Petition
No. 9F0770 (1964, 1962).
Witherup and Ushry, Kettering Laboratory, EPA Pesticide Petition No.
9F0770 (1965).
56
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PART II. INITIAL SCIENTIFIC REVIEW
SUBPART C. FATE AND SIGNIFICANCE IN THE ENVIRONMENT
CONTENTS
Page
Effects on Aquatic Species 58
Fish 58
Laboratory Studies 58
Field Studies 58
Lower Aquatic Organisms 58
Effects on Wildlife 60
Effects on Beneficial Insects 61
Interactions with Lower Terrestrial Organisms 64
Residues in Soil 64
Laboratory Studies 64
Field Studies 66
Monitoring Studies 67
Residues in Water 67
Residues in Air 67
Residues in Nontarget Plants 67
Bioaccumulation, Biomagnification 67
Environmental Transport Mechanisms .' 68
References 69
57
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This section contains data on the environmental effects of crotoxyphos,
including effects on aquatic species, wildlife and beneficial insects, inter-
actions with lower terrestrial organisms and effects on residues in soil,
water and air. The section summarizes rather than interprets scientific
data reviewed.
Effects on Aquatic Species
Fish -
Laboratory Studies - The toxicity of crotoxyphos to fish has been
evaluated and the results are summarized in Table 15.
Field Studies - Reports were not found on the effects of crotoxyphos
on fish under field conditions.
Commercial labels of crotoxyphos-containing formulations state that
the product is toxic to fish and warn against contaminating water by run-
off, cleaning of equipment, disposal of wastes, or other means.
Lower Aquatic Organisms - The toxicity of crotoxyphos to estuarine
animals was studied in 1966 at the biological laboratory at Gulf
Breeze, Florida, which at that time belonged to the U.S. Bureau of
Commercial Fisheries (Lowe, 1966).—' Brown shrimp (Penaeus aztecus)
were exposed for 48 hr to crotoxyphos concentrations ranging from
0.001 to 1.0 ppm in natural flowing seawater at a temperature of
68°F, salinity of 31%. The EC5Q in ppm was determined by percent
mortality or paralysis of the shrimp at the end of the observation
period. Under these experimental conditions, the following EC^Q
levels were determined for crotoxyphos:
24 hr exposure - 0.20 ppm
48 hr exposure - 0.032 ppm
In 1965 at the same laboratory, the effects of crotoxyphos on the
Eastern oyster, (Crassostrea virginica), were tested at a temperature of
82°F and salinity of 28%. Possible decrease in shell deposition during a
96-hr exposure period was observed as an indicator of adverse effects.
At the highest rate tested, 1.0 ppm, crotoxyphos did not aversely affect
the Eastern oyster under these experimental conditions.
I/ Lowe, J. I., "Bioassay Screening Test-Ciodrin," Bureau of Commercial
~ Fisheries Biological Laboratory, Gulf Breeze, Florida (unpublished
data, 1966).
58
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Table 15. ACUTE AND SUBACUTE TOXICITY OF TECHNICAL
CROTOXYPHOS TO FISH
Exposure
Specie
Sheepshead minnow
(Cyprinodon variegatus)
Bluegill (1.1 g)
(Lepomis macrochirus)
Channel catfish (1.1 g)
(Ictalurus punctatus)
Cutthroat trout (1.0 g)
(Salmo clarki)
Rainbow trout (1.0 g)
(Salmo gairdneri)
Fathead minnow (1.03 g)
(Pimephales promelas)
Largemouth bass (0.65 g)
(Micropterus salmoides)
time
(hr)
24
48
24
96
24
96
24
96
24
96
24
96
24
96
Toxic ity
Toxic ity value
measure (ppb) References
ECcQ > 1 ppm
EC^Q > 1 ppm
LC50* 390
(338-450)
LC5Q 152
(126-183)
LC5(/ 3,700
LC50 2,600
LC50 ^ 92
(49-170)
LC5Q 51
(28-94)
LC50~ 101
(82.4-124)
LC50 72.4
(60.0-87.4)
LC50* 15,500
(12,800-18,700)
LC5Q 11,900
(9,830-14,400)
LC50** 1,800
LC50 1,100
a/
k/
b/
k/
k/
k/
k/
k/
k/
k/
* At 17°C, pH 7.1.
/ At 18°C, pH 7.1.
t At 13°C, pH 7.1.
** At 18°C, pH 7.75.
a/ Lowe, op. cit. (1966).
b/ Johnson, W. W., "Toxicity of Ciodrin to Select Species of Fish and
Invertebrates," unpublished data, Fish-Pesticide Research Labora-
tory, Fish and Wildlife Service, U.S. Department of the Interior,
Columbia, Missouri (undated).
59
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The Fish-Pesticide Research Laboratory, Bureau of Sport Fisheries
and Wildlife, (1974) ,i/ studied the effects of crotoxyphos on the scud
( Gamma rus spp.)> and the stonefly (Pteronarcys spp.). Scuds were exposed
for 48 hr at 60.8°F, pH 7.4, 35 mg/liter alkalinity, and 40 mg/liter
hardness. Under these conditions, the reported LC5Q was 10 to 100
/ig/liter at 24 as well as at 48 hr. Stoneflies were exposed for 96 hr
under the same test conditions as in the Gammarus studies. The LCso was
1.0 to 10.0 yg/liter at 24 hr and at 96 hr.
Additional observations on the toxicity of crotoxyphos to scuds,
(Gammarus lacustris) . were reported by Sanders (1969) .2/ in static
bioassay tests, mature scuds were exposed for 96 hr at 70°F in test
water at pH.7.1, containing 88.0 ppm total dissolved solids, 30.0
ppm total alkalinity, 7.1 ppm calcium, and 3.1 ppm magnesium. The LCc/j of
crotoxyphos was 49 yg/liter at 24 hr, 29 yg/liter at 48 hr, and 15 yg/liter
at 96 hr. The corresponding 95% confidence limits were 36 to 67, 21 to 41,
and 14 to 20 yg/liter, respectively.
Butler (1964)A/ reported that there was decrease in productivity of
natural phytophlankton communities during a 4-hr exposure to a concentra-
tion of 1.0 ppm of Ciodrin.
Effects on Wildlife
The oral LDso for 3-to-4 month old mallard drakes (Anas platyrhynchos)
is 790 mg/kg with 95% confidence limits of 411-1520 mg/kg (Tucker and
Crabtree, 1970) .A/
Commercial labels of insecticides containing crotoxyphos as active
ingredient contain the caution statement: "This product is toxic to
fish and wildlife. Apply this product only as specified on this label."
I/ Fish-Pesticide Research Laboratory, Bureau of Sport Fisheries and
Wildlife, U.S. Department of the Interior, Columbia, Missouri.
Unpublished Laboratory Bioassay Screening Test Data (1974).
2J Sanders, H. 0., "Toxicity of Pesticides to the Crustacean Gammarus
lacustris," Technical Paper No. 25, pp. 18, U.S. Department of the
Interior, Fish and Wildlife Service (1969).
3/ Butler, P. A., "Fishery Investigation," Pesticide-Wildlife Studies.
1963, U.S. Fish Wildl. Serv. Circ., 199:5-28 (1964).
'kj Tucker, R. K., and D. G. Crabtree, Handbook of Toxtcity of Pesticides
to Wildlife, Bureau of Sport Fisheries and Wildlife, Denver Wildlife
Research Center, Resource Publication No. 84 (1970).
60
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Effects on Beneficial Insects
Atkins et al. (1973)!/ summarized the results of toxicity tests in
which a large number of pesticides and other agricultural chemicals were
studied in regard to their effects on the honeybee, (Apis mellifera).
In a laboratory procedure which primarily measures a chemical's contact
effect, pesticides were applied in dust form to groups of 25 bees per test
dose, three replicates per each of three colonies, for a total of nine
replicates per test dose. The procedure permits determination of an
LD50 value for each pesticide in micrograms of chemical per bee.
Honeybees were exposed to crotoxyphos for 48 hr at 80°F and 65%
relative humidity. Under these test conditions, the LD5Q of crotoxyphos
was 2.26 pg per bee, placing it into Group II, "Moderately Toxic to Honey-
bees." Anderson et al. (1971)2J define moderate honeybee toxicity as "able
to be used around bees if dosage timing, and method of application are
correct; direct application should not be made to exposed bees in the
field or at the colonies."
In their test procedure, Atkins et al. (1973) also determined the
slope of the dosage-mortality curve for each pesticide tested and recorded
it as a "slope value" in terms of probit units. Pesticides with a slope
value of four probits or higher can often be made safer to honeybees by
lowering the dosage only slightly. Conversely, by increasing the dosage
only slightly, the pesticide can become highly hazardous to bees.
Crotoxyphos rated an unusually high "slope value" of 17.10, indicating that
small changes in dosage rate would produce large changes in bee toxicity.
However, since honeybees do not usually search on or near livestock,
the only environment where crotoxyphos is registered for use, its toxicity
to honeybees (or lack thereof) is of limited significance.
Axtell (1966)1.' studied the toxicities of several insecticides includ-
ing crotoxyphos to housefly (Musca domestica) larvae and to a mite predator
of the housefly (Macrocheles muscaedomestica).
I/ Atkins, E. L., E. A. Greywood, and R. L. Macdonald, Toxicity of
Pesticides and Other Agricultural Chemicals to Honeybees.
University of California, Agricultural Extension Report M-16,
37 pp. (1973).
2/ Anderson, L. D., E. L. Atkins, Jr., H. Nakakihara, and E. A. Greywood,
Toxicity of Pesticides and Other Agricultural Chemicals to Honey Bees,
University of California, Agricultural Extension Service, Riverside,
Calif. (1971).
3f Axtell, R. C., "Comparative Toxicity of Insecticides to Housefly Larvae
and Macrocheles muscaedomestica. a Mite Predator of the Housefly,"
J. Econ. Entomol.. 59(5):1128-1130 (1966).
61
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Predaceous mites of the family Macrochelidae are common in the manure
of dairy cattle and poultry where the housefly often breeds. The mites
prey on the eggs and first-instar larvae of the housefly and are important
biological agents in suppressing fly populations. Thus, they are important
elements in the development of integrated housefly management programs.
Adult female Macrocheles muscaedomestic and third-instar larvae of
the housefly were exposed to the test insecticides incorporated into CSMA
fly rearing medium. Crotoxyphos was used in the form of an emulsifiable
concentrate. Three replications of each of five or six concentrations of
an insecticide were tested on day 1. This procedure was repeated on given
days. Each concentration-mortality curve is based on the combined results
of 9 to 12 replications. Concentrations are expressed in wt/wt percent.
Dosage-mortality regression lines were determined by probit analysis with
the maximum likelihood procedure.
Results obtained for crotoxyphos were as follows:
LC50 95% Confidence limits Slope
Fly larvae 0.018% 0.014-0.022% 1.045
Mites 0.016% 0.015-0.018% 3.125
Ratio of fly: mite LC50 1:1; LC95 12:1.
Thus, crotoxyphos was relatively more toxic to the mites than to the
fly larvae. Axtell points out that extrapolation from the laboratory
results to the field is complicated by several factors, including longer
exposure periods, exposure of additional stages of the mites and flies,
interactions between the manure and the insecticide, and fluctuating
environmental conditions.
In a follow-up experiment, Axtell (1968)1/ studied the populations of
housefly larvae and predaceous mites in poultry manure after larvicide
treatment under field conditions, i.e., after application of 12 insecti-
cides (including crotoxyphos) to the manure under caged laying hens.
17 Axtell, R. C., "Integrated Housefly Control: Populations of Fly
Larvae and Predaceous Mites, Macrocheles muscaedomesticae, in
Poultry Manure After Larvicide Treatment," J. Econ. Entomol.,
61(l):245-249 (1968).
62
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Each treatment was replicated four to six times. The numbers of
adult mites and third-instar housefly larvae were counted before and at
intervals after treatment.
Crotoxyphos was applied at a concentration of 1.0% by sprinkling can
at the rate of 0.5 liter/m^ to manure 60 cm deep. Mean numbers of mites
and fly larvae per sample were as follows:
Days after treatment
Pretreatment 5 13
Mites 37.1 38.3 25.6
Fly larvae 32.3 70.6 2.8
As indicated by these data, crotoxyphos had little effect on the mite
populatipn, and no adverse effect on the fly population 5 days after treat-
ment. According to the Axtell, the decline in fly larvae 13 days after
treatment was probably due to causes other than the insecticide treatment.
In a second experiment, crotoxyphos was again applied at a concentra-
tion of 1.0% by sprinkling can at the rate of 0.5 liter/m^ this time to
manure 5 cm deep. Numbers of mites and fly larvae were determined at
intervals of 5 to 30 days after treatment. Results in this test (mean
numbers of mites or fly larvae per sample) were as follows:
Days after treatment
Pretreatment 5 14 21 30
Mites 143.0 60.3 109.9 32.4 66.8
Fly larvae 137.0 115.0 90.4 114.0 131.0
63
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Interactions with Lower Terrestrial Organisms
Reports were not found on the effects of crotoxyphos on lower
terrestrial organisms, or on the effects of such organisms on the
insecticide.
Residues in Soil
Laboratory Studies - Konrad and Chesters (1969)!/ studied the degradation
of crotoxyphos in three different soils, Poygan silty clay loam (33.6%
clay; 10.0% organic matter; pH 7.2); Kewaunee clay (48.7% clay, 3.8%
organic matter; pH 6.4); and Ella loamy sand (5.2% clay; 1.6% organic
matter; pH 3.8). Analytical grade and ^C-labeled crotoxyphos were
used. Samples were extracted with benzene. Gas chromatography was
used to verify that the ^C-activity extracted arose entirely from
crotoxyphos. Presence of water-soluble degradation products was de-
termined as the difference between total and benzene-extractable
activity.
The half-lives of crotoxyphos in hours were as follows:
Nonsterile Sterile
Poygan silty clay loam 2.00 3.75
Kewaunee clay 5.50 6.00
Ella loamy sand 71.0 77.0
The degradation rates followed first-order kinetics and were related
to the extent of initial insecticide adsorption by the soils. In each of
the three soils, the degradation rate was somewhat slower in the electron
beam-sterilized soils but this was due to decreased crotoxyphos adsorp-
tion resulting from the irradiation treatment, rather than from retarda-
tion of microbial degradation processes. The first-order rate constants
for degradation of crotoxyphos were directly related to adsorption and
were the same for sterile and nonsterile soils for constant adsorption
in a given soil. Between soils, even at constant adsorption, the rates
I/ Konrad, J. G., and G. Chesters, "Degradation in Soils of Ciodrin, an
Organophosphate insecticide." J. Aer. Food Chem.. 17(2):226-230
(1969).
64
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of crotoxyphos degradation were variable^. The high acidity of the Ella
soil may have retarded the rate of degradation.
s
Further studies by Konrad and Chesters (1969) concerning the pathways
of chemical breakdown of crotoxyphos indicated that dimethylphosphorice
acid, cis-hydroxycrotonic acid, and 1-phenylethanol are the major degra-
dation products of crotoxyphos breakdown in soils.
Getzin and Rosefield (1968)17 studied the effects of a heat-labile
substance in soil on the degradation of crotoxyphos and several other
organophosphate insecticides. Chehalis clay loam was sterilized by gamma
radiation, heat, or a combination of the two methods, in 4-oz prescription
bottles, each containing 10 cc of moist soil. Crotoxyphos was then applied
at rates of 15 to 25 ug/cc of soil with sufficient water to maintain the
soil samples at their moisture equivalent. The bottles were then capped
and agitated to distribute the insecticide throughout the soil, and samples
were kept at 25°C for the desired periods of time before extracting the
pesticide residues. After extraction by appropriate solvents and proce-
dures, insecticide residues were measured by GIC.
Crotoxyphos, along with two other insecticides, was among the least
stable compounds tested. After an incubation period of 1 day, 4% of the
initial quantity of crotoxyphos were degraded in the autoclaved soil;
34% in the irradiated soil; and 87% in the nonsterile soil. All insecti-
cides studied degraded more rapidly in nonsterile than in the heat- or
irradiation-sterilized soils, suggesting that microorganisms were partlv
responsible for degradation. With only one exception, all insecti-
cides studied, including crotoxyphos, degraded more rapidly in the
irradiated than in the heat-sterilized soil. The authors suggest that
this may be due to the action of a heat-labile, nonviable, water-soluble
substance. Further studies were performed to characterize this substance,
and it was determined that it was destroyed by heating soil suspensions
for 10 min at 90°C but most of its activity was retained in soils held at
25°C for 2 to 3 months after radiation sterilization.
I/ Getzin, L. W., and I. Rosefield, "Organophosphorus Insecticide
Degradation by Heat-Labile Substances in Soil," J. Agr. Food Chem..
16(4):598-601 (1968).
65
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Helling et al. (1971)^ offer an interesting alternate explanation
for the observations reported by Getzin and Rosefield (1968). They
point out'that there exists yet another mechanism of pesticide degradation
in soils which may be influenced by different soil sterilization techniques,
i.e., the reaction of pesticides with free radicals in the soil. Free
radical content in the soil is reduced by autoclaving, but increased by
gamma irradiation. Thus, the results reported by Getzin and Rosefield
might have been due to the creation of more highly reactive free radicals
by soil irradiation. These radicals would be destroyed by high tempera-
ture and therefore appear to be "heat-labile." According to Helling et al
(1971), Konrad and Chesters (1969) did not compare the degradation of cro-
toxyphos in autoclaved versus irradiation-sterilized soils, but the rates
of crotoxyphos degradation which they reported for the sterile soils may
also have been promoted by the free radical process.
Field Studies -
Reports were not found on field studies dealing with crotoxyphos
residues in soil.
I/ Helling, C. S., P. C. Kearney, and M. Alexander, "Behavior of Pesti.
cides in Soil«," Advances in Agronomy. 23:147-240 (1971).
66
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Monitoring Studies -
Since the results of the 1972 National Monitoring Program for
pesticides has not yet been published, data from this source could
not be included. No other monitoring studies of crotoxyphos were found.
Residues in Water
Konrad and Chesters (1969) reported the following half-life values
for the hydrolysis of crotoxyphos in water: 540 hr at pH 2.0; 410 hr at
pH 6.0; 180 hr at pH 9.0. This data shows that hydrolysis is faster in
alkali than in near-neutral solution and/or acid solutions. (Temperature
was not specified.) The solution pH values were adjusted with hydrochloric
acid or sodium hydroxide, and apparently were not buffered. Beynon et al.
(1973)—' point out that these half-lives are considerably longer than those
found in contact with soil. Porter (1967)—' studied the hydrolysis of
crotoxyphos at 38°C and found that hydrolysis was moderately rapid under
alkaline or strongly acid conditions.
Shell Chemical Company (1972)^.' states that crotoxyphos decomposes
moderately fast in the presence of water, and that its half-life in aqueous
solution at 100°F ranged from 35 hr at pH 9 to 87 hr at pH 1 (these values
are apparently taken from Porter, 1967).
Residues in Air
No other data on the presence, fate, or persistence of crotoxyphos
in air was found.
Residues in Nontarget Plants
Reports were not found on the possible effects of crotoxyphos on
nontaxget plants or on the occurrence of residues in such plants.
Bioaccumulation, Biomagnification
Reports were not found on the possible bioaccumulation or biomagnifica-
tion of crotoxyphos.
I/ Beynon, K. I., D. H. Hutson, and A. N. Wright, "The Metabolism and
Degradation of Vinyl Phosphate Insecticides," Residue Rev. 47:55-142
(1973). n
21 Porter, P. E., "CiodrinQy Insecticide," In: G. Zweig (ed.): Analytical
Methods for Pesticides, Plant Growth Regulators, and Food Additives.
Vol. V, p. 243. Academic Press, Inc., New York (1967).
3/ Shell Chemical Company, "Summary of Basic Data for Technical Ciodrin
Insecticide," Agr. Division, Technical Data Bulletin ACD:62-1,
San Ramon, Calif. (1972).
67
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Environmental Transport Mechanisms
No data was found on environmental transport mechanisms of crotoxyphos,
Howeyer, there is one related report in this area. Sun (1971)—'
suggested relationships between the speed of action of insecticides on the
housefly (Musca domestica), and the occurrence of residues in fat and milk.
Organophosphate insecticides generally act faster than organochlorine
insecticides on insects and other animals.- Differences in respective
rates of penetration and detoxication determine the speed of action. Sun
points out that an unstable, quick-penetrating insecticide would show
little difference in LCso values between short-and long-time exposures.
He used the ratio of the ICcg values between 3 hr and 22 hr exposure as
an index for the speed of action. When crotoxyphos was tested on house-
flies by a residue-file method, its LCso (ug/jar) was 5.5 for an exposure
period of 3 hr; 4.6 for 22-hr exposure, resulting in a "speed index" of
1.2. This value is at the lower end of the scale for organophosphate
insecticides. The "speed indices" of the 36 organophosphates insecticides
tested in this manner ranged from 0.93 to 3.5,
JL/ Sun, Y. P., "Speed of Action of Insecticides and Its Correlation
with Accumulation in Fat and Excretion in Milk," J. Econ. Entomol..
64(3):624-630 (1971).
68
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References
Anderson, L. D., E. L. Atkins, Jr., H. Nakaklhara, and E. A. Greywood,
Toxicity of Pesticides and Other Agricultural Chemicals to Honeybees.
University of California, Agricultural Extension Service, Riverside,
Calif. (1971).
Atkins, E. L., E. A. Greywood, and R. L. Macdonald, Toxicity of
Pesticides and Other Agricultural Chemicals to Honeybees,
University of California, Agricultural Extension Report M-16,
37 pp. (1973).
Axtell, R. C., "Comparative Toxicity of Insecticides to Housefly Larvae
and Macrocheles muscaedomestica. a Mite Predator of the Housefly,"
J. Econ. Entomol.. 59(5):1128-1130 (1966).
Axtell, R. C., "Integrated Housefly Control: Populations of Fly Larvae
and Predaceous Mites, Macrocheles muscaedomesticae, in Poultry Manure
After Larvicide Treatment," J. Econ. Entomol.. 61(1):245-249 (1968).
Beynon, K. I., D. H. Hutson, and A. N. Wright, "The Metabolism and
Degradation of Vinyl Phosphate Insecticides," Residue Rev. 47:55-142
(1973) .
Butler, P. A., "Fishery Investigations." Pesticide - Wildlife Studies. 1963.
U.S. Fish. Wildl. Serv. Circ., 199:5-28 (1964).
Fish-Pesticide Research Laboratory, Bureau of Sport Fisheries and
Wildlife U.S. Department of the Interior, Columbia, Missouri.
Unpublished Laboratory Bioassay Screening Test Data (1974).
Getzin, L. W., and I. Rosefield, "Organophosphorus Insecticide Degradation
by Heat-Labile Substances in Soil," J. Agr. Food Chem.. 16(4):598-601
(1968) .
Helling, C. S., P. C. Kearney, and M. Alexander, "Behavior of Pesticides
in Soils," Advances in Agronomy. 23:147-240 (1971).
Johnson, W. W., "Toxicity of Ciodrin to Select Species of Fish and
Invertebrates," unpublished data, Fish-Pesticide Research Labora-
tory, Fish and Wildlife Service, U.S. Department of the Interior,
Columbia, Missouri (undated).
Konrad, J. G., and G. Chesters, "Degradation in Soils of Ciodrin, an
Organophosphate Insecticide," J. Agr. Food Chem.. 17(2):226-230 (1969).
69
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Lowe, J. I., "Bioassay Screening Test-Ciodrin," Bureau of Commercial
Fisheries Biological Laboratory, Gulf Breeze, Florida (unpublished
data, 1966).
Porter, P. R. , "Ciodrin Insecticide ," In: G. Zweig (ed.); Analytical
Methods for Pesticides, Plant Growth Regulators, and Food Additives,
Vol. V, p. 243. Academic Tress ,~IncV," New York (1967TT
Sanders, H. 0., "Toxicity of Pesticides to the Crustacean Gamma r us
lacustris." Technical Paper No. 25, pp. 18, U.S. Department of the
Interior, Fish and Wildlife Service (1969) .
Shell Chemical Company, "Summary of Basic Data for Technical Ciodrin
Insecticide," Agr. Division, Technical Data Bulletin ACD:62-1,
San Ramon, California (1972) .
Sun, Y. P., "Speed of Action of Insecticides and Its Correlation
with Accumulation in Fat and Excretion in Milk," J« Econ. Entomol..
64(3):624-630 (1971).
Tucker, R. K. , and D. G. Crabtree, Handbook of Toxicity of Pesticides
to Wildlife. Bureau of Sport Fisheries and Wildlife, Denver Wild-
life Research Center, Resource Publication No. 84 (1970).
70
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PART II. INITIAL SCIENTIFIC REVIEW
SUBPART D. PRODUCTION AND USE
CONTENTS
Page
Registered Uses of Crotoxyphos 72
Federally Registered Uses 72
State Regulations .....' 78
Production and Domestic Supply .... 78
Volume of Production 78
Imports 79
Exports 80
Domestic Supply 80
Formulations 80
Use Patterns of Crotoxyphos in the United States 81
General 81
Crotoxyphos Use Patterns by Regions 83
Crotoxyphos Uses in California 85
References 87
71
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This section contains information on the registration status, and
on the production and uses of crotoxyphos. The section summarizes rather
than interprets data reviewed.
Registered Uses of Crotoxyphos
Federally Registered Uses - Crotoxyphos is an organic phosphate insecti-
cide that acts as a contact and stomach poison. By virtue of its
spectrum of insecticidal effectiveness and relatively "moderate" mam-
malian toxicity, it is useful for the control of external parasites on
livestock, including flies, lice, and ticks. The chemical's potential
as an insecticide was first recognized about 1960 by the Shell Chemical
Company. It progressed through various research and development stages
and has been commercially available as a livestock insecticide since the
mid-1960's.
The registered uses of crotoxyphos by principal formulations, animal
species, established tolerances, dosage rates, and use limitations are
outlined below.—'
Crotoxyphos is registered and recommended for use on beef cattle,
dairy cattle, goats, sheep, and swine, and for the treatment of agri-
cultural premises including barns, dairy barns, ^fences, fly breeding
areas, and other farm buildings except poultry houses. The product is
available in a number of different formulations, as outlined in greater
detail in the subsection on formulations (page 23). Crotoxyphos is used
on animals as a spray or fog in water or in oil, or as a dust.
On beef and dairy cattle, crotoxyphos may be used as follows:
1. 1.0% active ingredient in water at the rate of 1 to 2 pints per
adult animal (proportionately less for smaller animals); may be
repeated, but not more often than every 7 days. Concentration
and volume per animal may be varied inversely; for instance,
0.5% active ingredient may be applied at the rate of 1 to 2
quarts per animal; 0.25% active ingredient at up to 1 gal per
animal; 0.1% active ingredient at up to 2 gal per animal.
I/ U.S. Environmental Protection Agency, EPA Compendium of Registered
Pesticides. Vol. Ill, p. D 46.1-D 46.3.
72
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2. 2.0% active ingredient in water may be applied daily at the rate
of 1 to 2 oz per animal.
3. 1.0% active ingredient in water may be applied up to three times
per week at the rate of 15 teaspoonfuls sprayed to face and a
total of 5-10 teaspoonfuls sprayed to back and sides of animal.
4. 1.0% active ingredient in oil may be applied as a spray at
the rate of 3.5 fluid ounce per animal, two applications at
14-day intervals; as a spray at the rate of 2 fluid ounce per
animal daily; or by back rubbers, without time limitations.
5. Dust containing 3% active ingredient may be used at the rate of
one to two heaping tablespoonfuls per animal on poll, back and
upper portions of sides, not more often than every 2 weeks; or
as a thorough treatment of the entire animal (for louse control),
not to be repeated within less than 3-to-4 weeks (this treat-
ment not permitted on calves under 6 months of age); or by way
of dust bags suspended in livestock holding pens, feedlots,
loafing sheds, near mineral or salt licks, and in alleyways
leading to and from animal buildings or dairy farms; without
time limitations.
The following use patterns are registered for use on goats, sheep,
and swine:
1. 1.0% active ingredient in water at the rate of 1 pint per animal
per application, not to be repeated in less than 7 days. For
this use pattern, concentration and volume of spray per animal
are somewhat interchangeable; 0.5% active ingredient in water
may be applied at the rate of 1 quart per animal per application;
or 0.25% at up to 1 gal. of spray per animal; or up to 2 gal.
per animal of 0.1% spray.
2. 1.0% active ingredient in water may be applied at the rate of
15 teaspoonfuls to the face and a total of 5 to 10 teaspoonfuls
to back and sides of animals, to be repeated not more than three
times per week.
3. 0.25% active ingredient in oil may be applied (to swine only)
at the rate of 1 fluid ounce per animal, without time limitations.
73
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4. Dusts containing 3% active ingredient may be applied to swine
at the rate of 1 to 2 oz as thoroughly as possible, especially
to the neck and area around the ears, to be repeated in 3 to 4
weeks if necessary.
For the control of pest insects in and around agricultural premises,
crotoxyphos is registered and recommended as follows:
1. 1.0% active ingredient as an aqueous spray at the rate of 1 gal
per 1,000 ft2 of surface area.
2. 0.25% in oil as a fog, at the rate of about 2 fluid ounces per
1,000 ft2 (not to be applied in areas where animals have been
directly treated with DDVP within the last 8 hr).
Crotoxyphos by itself is not registered for use as a livestock dip,
for use on poultry, in poultry houses, nor for use on pets, based on
information provided by the basic producer, Shell Chemical Company. For
an overview of the economically and ecologically most important registra-
tions, including dosage rates, general and specific directions for use,
types of equipment, use limitations, caution statements, and other details
pertinent to commercial use, specimen labels for two typical crotoxyphos
liquid formulations are included in this section, i.e., a dairy spray con-
centrate containing 21.5% crotoxyphos for dilution with water, as illustra-
ted in Table 16, and a ready-to-use oil base dairy spray containing 1.0%
crotoxyphos and a 0.23% DDVP (dichlorvos), as illustrated in Table 17.
Tolerances established for residues of crotoxyphos are recorded in
the Code of Federal Regulations. Title 40, Part 180.280. Tolerances have
been established for meat, fat and meat by-products of cattle, goats, hogs,
and sheep, and for milk.
Several regional formulators combine crotoxyphos with other insecti-
cides. Among these combinations, crotoxyphos with DDVP at the ratio of
four parts of crotoxyphos to one part of DDVP is most widely used.
Crotoxyphos-DDVP combination formulations are generally registered and
recommended for the same insect control purposes as crotoxyphos by itself.
The DDVP component provides more rapid extermination of target insects.
At least one brand label of an emulsifiable concentrate formulation
of crotoxyphos containing 14.4% of active ingredient includes recommendations
for the control of stable flies on horses (Roberts Laboratories, Inc.,
Rockford, Illinois 61101).
At least one ready-to-use crotoxyplios (1.0%)-DDVP (0.25%) combination
formulation in oil is recommended not only for use on dairy and beef cattle,
but also for the control of flies, gnats, mosquitoes, fleas, and brown dog
ticks in kennels; as a spray to be applied outside of dog runways, window
sills and ledges (but not on dogs directly); and against maggots breeding
in garbage dumps, manure piles, and other breeding areas.
74
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Table 16. CROTOXYPHOS 21.5% SPRAY CONCENTRATE LABEL
Ol
HOW TO USE PURINA DAIRY SPRAY CONCENTRATE
For Dairy Cattle— Beef Cattle— Sheep— Goats— Hogs
For Control of Stable Flies. House Files. Horn Flies, and Face Files on Dairy and Beef Cattle:
Using low pressure equipment (compression sprayer, knapsmck sprayer)— Mi* 1 pint of Dairy
Spray Concentrate in 2)4 gallons or water (i K oz. per gallon). Spray to thoroughly cover all parts of
the animal, including the legs, using 1 to 2 pints of spray per large animal and proportionately less
for small animals.
Using high pressure equipment (hydraulic sprayer for pen or corral operations)— Mix 1 pint of
Dairy Spray Concentrate in 5 gallons of water. Spray to thoroughly cover the anlmaTa body and legs
(avoid excessive spraying of the head) using 1 to 2 quart* of spray per large animal and proportion-
ately less for smaller animals.
Repeat above application as necessary to maintain control, but not more often than once every 7 day*
for either low or high pressure equipment.
To improve face fly control, add H pound of sugar per & gallons of spray.
Using hand atomizer sprayer— Mix 3 ox. (6 tabhspoonfuls) of Dairy Spray Concentrate per quart
of water. Spray to thoroughly cover all parts of the animal, including the lees. Use 1-2 fluid ounces of
spray per animal daily. To improve face fly control, add 2 level tablespoons of sugar per quart of spray.
For Control of Lice, Lone Star Ticks, and Winter Ticks on Dairy Cattle, Beef Cattle, Sheep,
Goats and Hogs: Mix 1 pint of Dairy Spray Concentrate In 10 gallons of water. Spray animals
thoroughly using up to 1 gallon of spray per large animal and proportionately less for smaller animals.
Apply a second application U days later. Repeat applications as necessary to maintain control.
For Cattle Rubbing Devices: For the control of horn flies and face files: Mix 1 pint of Dairy
Spray Concentrate in 3 gallons of 12 fuel oil or dfcsel fuel oil. Install rubbing devices in areas where
the animals loaf, feed, or water.
WARNING: HAZARDOUS IF SWALLOWED. INHALED, OR ABSORBED THROUGH SKIN.
Hazardous or fatal if swallowed. If swallowed, induce vomiting. Call a physician Immediately. Vapor
harmful. Hazardous if absorbed through the skin. Atropine is antidotal.
Wash thoroughly with soap and water after handling and before eating and smoking. Wear clean
clothing. In case of spillage on person or clothing, immediately remove clothing and flush skin or eyes
with plenty of water; for eyes get medical attention. Keep away from heat and open flame.
Do not apply regularly to calves under 6 months of age. Brahman cattle should not be treated as they
may show hypcrscnsitfvity to organic phosphate. Do not contaminate feed, foodstuffs, or drinking
wafer. During commercial or prolonged exposure in spray-mixing and loading operations, wear clean
synthetic rubber gloves and a mask or respirator of a type approved by the U. S. Bureau of Mines for
protection against Ciodrln* Insecticide. Use this material only for recommended purposes and at
recommended dosages.
This product is toxic to fish and wildlife. Apply this product only as specified on this label.
Rinse equipment and containers and dispose of waste* and soil contaminated by spillage by burying
in non-crop lands away from water supplies. Containers should be disposed by punching holes in them
and burying with wastes.
DO NOT USE, POUR, SPILL OR STORE NEAR HEAT OR OPEN FLAME
D-2532 EPA Esl. 602-MO-l Printed In U.S.A.
NET CONTENTS: 16 FL. OZ. (1 PT.) E.P.A. Reg. No. 602-101-AA
'7110H
QUALITY CONTROLLED BY PURINA RESEARCH
1 PINT MAKES UP TO 10 GALLONS OF SPRAY
FOR CONTROL OF: FACE FLIES-STABLE FLIES-HORN FLIES-
HOUSE FLIES-LICE-LONE STAR TICKS-WINTER TICKS
Active Ingredients:
Dimethyl phosphate of alpha-methylbenzyl
3-hydroxy-cia-crotonate 21.5%
Xylene 67.4%
Inert Ingredient* 11.1%
•Reg. T. M. Shell Chemical Company 100.0%
WARNING: KEEP OUT OF REACH OF CHILDREN
SEE OTHER WARNINGS ON BACK PANEL •
Manufactured 6y RALSTON PURINA COMPANY
GENERAL OFFICES • CHECKERBOARD SQUARE . ST. LOUIS. MO. Mltt
Source: Label for "Purina Dairy Spray Concentrate"
EPA Reg. No. 602-101-AA (1 pint container)
Ralston Purina Company, St. Louis, Missouri
-------
Table 17. CROTOXYPHOS 1% + DICHLORVOS 0.23% FLY SPRAY LABEL
Net Contents: 30 Gallon
EPA Reg. No. 602-1B3-AA
PURIfiMA*
®
D-2568
tUETWf
CAUTION: KEEP OUT OF REACH OF CHILDREN
See Other Cautions on Back Panel
READY-TO-USE OIL BASE FLY SPRAY
Kills House Hies, Stable Flies, Face Flies, Horn Hies, Lice on Dairy or Beef Cattle.
Active Ingredients:
Dimethyl Phosphate of Alpha methylbenzyl-3 Hydroxy-cis-Crotonate l.C
2.2-Dichloroviny) Dimethyl Phosphate** 0.2
Related Compounds** O.Q
Petroleum Oils 98.5
ioo!oo%
**Equt*«l«nt to 0.25% V«pon« InMCtlcId*
Manufactured by
RALSTON PURINA COMPANY
General Offices • St. Louis. Missouri 63188
-------
Table 17. (Continued)
HOW TO USE PURINA DAIRY SPRAY SPECIAL
Purina Dairy Spray Special is a ready-to-use oil base spray for
use in hand sprayers, misting equipment, and back or face rubbers.
Contains Ciodrin* and Vapona* Insecticides for effective knock-
down, kill and residual protection against flies and lice on dairy
or beef cattle. Do not apply on horses.
For Control of House Flies, Stable Flies, Horn Flies, and Face Flies:
Apply Dairy Spray Special as a mist to the hair coat by using a
hand atomizer-type sprayer or mechanical misting equipment.
Spray once daily using 1 to 2 ounces over the entire animal. Spray
calves more sparingly. Do not wet the skin.
For stable flies, spray legs and flanks; for face flies spray face and
head areas. Repeat once daily as necessary.
Back Rubbers and Face Rubbers: For the control of horn flies and
face flies on lactating dairy and beef animals:
Use 1 gallon of Dairy Spray Special for each 20 linear feet of
burlap back rubber. For automatic back rubbers recharge the
reservoir as needed. Animals must rub face on rubbers for best
face fly control.
For Control of Lice: Make 1 to 2 applications of 3-3H ounces of
Dairy Spray Special at 14 day intervals. Apply as a fine mist
spray to thoroughly cover all parts of the animal. If applied by
fogging or misting equipment, the maximum spraying time per
animal is 20 seconds.
CAUTION: Avoid inhalation of mist and contact with skin. In case
of contact with skin or eyes, flush with plenty of water, for eyes
get medical attention. Wash thoroughly with soap and water after
using, and before eating or smoking. Harmful or fatal if swallowed.
If swallowed, induce vomiting immediately and get medical atten-
tion. Atropine is antidotal. 2-PAM is also antidotal and may be
administered in conjunction with atropine.
Keep out of reach of children. Do not mist or fog into air of closed
buildings. Do not wet the skin of animals. Do not spray or store
near an open flame. Do not contaminate feed, water or foodstuffs.
This product is toxic to fish and wildlife. Birds feeding on treated
areas may be killed. Keep out of any body of water. Do not apply
where runoff is likely to occur. Do not contaminate water by clean-
ing of equipment, or disposal of wastes. Apply this product only
as specified on this labeL
Do not re-use empty container. Destroy container by perforating
and bury or discard in a safe place.
QUALITY CONTROLLED BY PURIEJA RESEARCH
717L
EPA Est 602-MO-l
P.-intod in U.SJL
Source: Label for "Purina Dairy Spray Special"
EPA Reg. No. 602-186-AA (30 gal. container)
Ralston Purina Company, St. Louis, Missouri
-------
Another combination formulation of note is a pressurized spray in
which crotoxyphos is combined with eight other "active ingredients,"
plus pine oil and mineral oil. The formula, labeled by Chem Spray
Aerosols, Inc., Houston, Texas 77088, includes- 1.0% crotoxyphos; 0.25%
dichlorvox and related compounds; 0.05% pyrethrins; 0.1% piperonyl
butoxide; 0.168% n-octyl bicycloheptene dicarboximide; stabilizer; and
petroleum distillate. This produce is used against biting flies
(including stable flies, horn flies, horse flies, and deer flies),
houseflies, mosquitoes and gnats on horses and ponies.
Another fly spray product, used only for dairy cows against stable
flies, horn flies, mosquitoes, and gnats, is a ready-to-use oil formula-
tion containing 1.0% crotoxyphos; 0.2% dichlorvos and related compounds;
0.03% pyrethrins; 0.11% technical piperonyl butoxide; plus petroleum
solvents (Watkins Products, Inc., Winona, Minnesota 55987).
State Regulations - Regarding mammalian toxicity, crotoxyphos is in the
"moderately toxic" category. Crotoxyphos is not subject to specific use
restrictions under State pesticide laws or regulations.
Production and Domestic Supply
Volume of Production - According to the United States Tariff Commission's
final reports on Synthetic Organic Chemicals for the years 1971, 1972,
and 1973,!/ there has been only one basic producer of crotoxyphos in the
United States, Shell Chemical Company, a Division of Shell Oil Company.
Shell Chemical Company's Agricultural Division through which crotoxyphos
is marketed is located in San Ramon, California.
In the Tariff Commission (TC) reports, the production and sales
volumes of crotoxyphos are not reported individually. Crotoxyphos is
included in the category of "pesticides and related products, cyclic"
in a classification entitled "all other organophosphorus insecticides."
This classification includes eight major, specified organophosphate
insecticides (not including crotoxyphos), and "other phosphorothioates
and phosphorodithioates, and others." The total production volume for
this classification, according to the Tariff Commission reports, was
36,740,000 Ib in 1971, 44,385,000 Ib in 1972, and 53,265,000 Ib in 1973.
I/ U.S. Tariff Commission, Synthetic Organic Chemicals. U.S. Production
and Sales, TC Publication 681 (1971, 1972, 1973).
78
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Compared to the major Insecticides in this category, the production
and sales volumes, of crotoxyphos are so small that the Tariff Commission
data is not significant in estimating crotoxyphos volumes.
Crotoxyphos was not included in two recent studies in which con-
siderable detail on the production volumes and use patterns of selected
pesticides was obtained (Lawless et al., 1972; von Rumker et al.,
1974).ill/
The U.S. Department of Agriculture (USDA, 1974)-3-/ reports that 901,000 Ib
of crotoxyphos active ingredient were used on livestock in the United States
in 1971 (141,000 Ib in 1966). Exports of crotoxyphos appear to be small in
volume, probably not exceeding 100,000 Ib active ingredient.
Based on USDA's estimate for the domestic consumption of crotoxyphos
in 1971, and assuming further that crotoxyphos exports in 1971 were 100,000 Ib
active ingredient or less, the total U.S. supply of the product in 1971, must
have been on the order of 0.9 to 1.0 million pounds active ingredient. Data
was not found on U.S. production or use of crotoxyphos. However, confidential
discussions with representatives of the manufacturer, Shell Chemical Company,
indicate these estimates are very high.
Imports - Imports of pesticides that are classified as "benzenoid chemicals"
are reported by the U.S. Tariff Commission in its 1973 report on benzenoid
chemicals .A'
I/ Lawless, E. W., R. von Rumker, and T. L. Ferguson, The Pollution
Potential in Pesticide Manufacturing, Pesticide Study Series - 5,
Environmental Protection Agency, Technical Studies Report: TS-00-
72-04 (1972).
2J von Rumker, R., E. W. Lawless, and A. F. Meiners, "Production, Distribution,
Use and Environmental Impact Potential of Selected Pesticides," Final
Report, Contract No. EQC-311, for Council on Environmental Quality,
Washington, D.C. (1974).
jj/ U.S. Department of Agriculture, Farmers' Use of Pesticides in 1971 . . .
Quantities, Agricultural Economic Report No. 252, Economic Research
Service (1974).
4/ U.S. Tariff Commission, Imports of Benzenoid Chemicals and Products.
1972, TC Publication 601 (1973).
79
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The Tariff Commission classifies crotoxyphos as a "benzenoid chemical."
According to the TC reports, there were no imports of crotoxyphos into the
United States in 1972. It is unlikely that significant, if any, quantities
of crotoxyphos. were imported in more recent or in previous years because
it xs covered by a patent of Shell Chemical Company, the sole U.S. producer.
Exports - Pesticide exports are reported annually by the Bureau of the
Census.£/ Technical or formulated crotoxyphos is not specifically listed
in any of the commodity descriptions applicable to pesticides in Section 5,
Chemicals (Revision 1/1/72). This is probably due to the following reasons:
1. Crotoxyphos exports, if any, are small in volume. (Usually,
only pesticides whose export volume is significant are listed
individually in the appropriate classifications.)
2. As a livestock insecticide, formulated crotoxyphos may have
been included in Section 599.2090 (Schedule B), "Agricultural
chemical preparations not elsewhere classified, including plant
growth regulators and similar type preparations." This category
includes prepared animal dips, cattle dips, sheep dips, stock
dips.
More specific information on the export volume of crotoxyphos could
not be obtained within the limitations of time and resources available.
Based on available information, Midwest Research Institute estimates that
the export volume of crotoxyphos for the last few years did not exceed
100,000 lb active ingredient.
Domestic Supply - Information reviewed indicates that the domestic consumption
of crotoxyphos in the United States in 1971, was about 900,000 lb active ingre-
dient. No data or estimates are available on the domestic consumption of cro-
toxyphos in 1972 or 1973, or in years between 1966 and 1971.
Formulations - Crotoxyphos by itself is available for commercial use in
the United States in a number of different formulations, including
eraulsifiable concentrates, oil solutions, dust concentrates, and dilute
dusts. Emulsifiable spray concentrates range in active ingredient
content from 1.0 to 4.0 Ib/gal. Several oil concentrates contain 14.4%
active ingredient. Many dilute, ready-to-use crotoxyphos-in-oil form-
ulations contain 1 or 2% active ingredient. Ready-to-use dust formu-
lations contain 3% active ingredient. The dry manufacturing concentrate
for local preparation of dilute dusts contains 80% active ingredient.
_!/ U.S. Bureau of the Census, U.S. Exports. Schedule B, Commodity by Country,
Report FT410.
80
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In addition, a number of multi-ingredient formulations are offered
in which crotoxyphos is combined with DDVP and/or synergized pyrethrins.
The most popular combination formulation, offered under a number of
different brand names and labels, appears to be one containing 1%
crotoxyphos and about 0.25% DDVP. Several suppliers offer other
crotoxyphos-DDVP combination formulations containing the two active
ingredients at the same ratio as the dilute formulations (four parts
of crotoxyphos to one part of DDVP). One typical product in this
category contains 13.03% crotoxyphos plus 3.22% DDVP.
Three-way combination formulations include a ready-to-use oil-based
dairy spray containing 1.0% crotoxyphos, 0.2% DDVP and related compounds,
0.03% pyrethrins, and 0.11% piperonyl butoxide; and a pressurized spray
containing 1.0% crotoxyphos, 0.25% DDVP and related compounds, 0.05%
pyrethrins, 0.1% piperonyl butoxide, 0.168% n-octyl bicycloheptene
dicarboximide, stabilizer, pine oil, mineral oil, and petroleum .distil-
late.
The 1972 and 1974 editions of the Pesticide Handbook—Entoma (Frear,
1972; and Billings, 1974)itl/ list a total of about 30 different products
containing crotoxyphos as an active ingredient, marketed by at least
12 different companies, including Shell. There are a number of additional
mostly smaller suppliers of crotoxyphos containing products not listed
in the Pesticide Handbook—Entoma.
Use Patterns of Crotoxyphos in the United States
General - Crotoxyphos is a specialty insecticide which is registered
in the United States only for the control of external parasites on
livestock. Pests controlled by crotoxyphos include stable flies,
horn flies, house flies, face flies, ticks, lice, and certain mites.
The product is not federally registered for any uses on agricultural or
other crops, for use on poultry or pets, nor for commercial, institutional,
or residential pest control purposes. Products in which crotoxyphos is
I/ Frear, D. E. H., ed., Pesticide Handbook—Entoma, 24th ed., College
Science Publishers, State College, Pennsylvania (1972).
2/ Billings, S. C., ed., Pesticide Handbook--Entoma» 25th ed.,
Entomological Society of America, College Park, Md. (1974).
81
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combined with other active ingredients carry additional insect control
claims, including control of, and/or repellent action against horse flies,
deer flies, mosquitoes, gnats, fleas and maggots.
Crotoxyphos has been in commercial use in the United States for
about 10 years. A U.S. Department of Agriculture report on pesticide
use by farmers in 1964i' does not include crotoxyphos among the insecti-
cides used by farmers on livestock. According to the pesticide use report
for 1966,±/ farmers used 141,000 Ib of crotoxyphos active ingredient that
year. In 1971, 901,000 Ib were used (USDA, 1974).
Data on the livestock uses of crotoxyphos in the U.S. by type of
livestock from the 1966 and 1971 USDA surveys is presented in Table 18.
This data indicates that in both years, close to 80% of the total quantity
of crotoxyphos used was applied to dairy cattle. Uses on beef cattle
accounted for an additional 13% in 1966; almost 20% in 1971. Much
smaller quantities of crotoxyphos were used on hogs, poultry, sheep, and
other livestock, according to these sources. Crotoxyphos is not regis-
tered for use on poultry.
Table 18. PROPORTIONS OF CROTOXYPHOS CONSUMPTION FOR DIFFERENT
LIVESTOCK USES IN THE U.S. IN 1966 AND 1971
Type of Year
livestock 196.6 1971
Percent
Dairy cattle 84.4 76.9
Beef cattle 12.8 19.6
Hogs 2.1 2.9
Poultry - .3
Sheep - .1
Other .!_ ^2
Total 100.0 100.0
I/ U.S. Department of Agriculture, Quantities of Pesticides Used by
Farmers in 1964, Agricultural Economic Report No. 131, Economic
Research Service (1968).
2/ U.S. Department of Agriculture, Quantities of Pesticides Used by
Farmers in 1966, Agricultural Economic Report No. 179, Economic
Research Service (1970).
82
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Crotoxyphos Use Patterns by Regions - Table 19 presents a breakdown of
the livestock uses of crotoxyphos in 1971, by geographic regions. The
information on the use by type of livestock is taken from the USDA's
survey of pesticide uses by farmers in the U.S. in 1971. The breakdown
by regions was obtained by reference to the density of the different
types of livestock in different parts in the U.S. (U.S. Department of
Agriculture, 1973; U.S. Bureau of the Census, 1973) .iti/ and from RvR
Consultants personal communications with trade sources.
According to Table 19, about 50% of the total domestic consumption
of crotoxyphos in 1971 was used in the North Central states. About
757. of this subtotal (i.e., 330,000 Ib) was used on dairy cattle, an
additional 100,000 Ib on beef cattle, and the small remaining balance on
hogs and other livestock.
The Northeastern states accounted for the next largest volume of
use of crotoxyphos in 1971, 144,000 Ib, that is about 16% of the total
U.S. use. More than 90% of the regional subtotal was used on dairy
cattle; the balance on beef cattle, hogs, and other livestock.
The South Central states ranked third; approximately 127. of the
national total, or 111,000 Ib of crotoxyphos were used in this area
in 1971. In this region, about 83,000 Ib, or about 757. of the regional
subtotal, were used on dairy cattle, an additional 25,000" Ib (about 22%)
on beef cattle, and the small remaining balance on hogs and other live-
stock.
Of the three remaining regions', the Southwest used approximately
76,000 Ib (8%); the Southeast about 63,000 Ib (7%); and the Northwest
about 56,000 Ib (6%) of crotoxyphos. As in the other areas, the largest
share of each regional subtotal was used on dairy cattle, followed by
beef cattle, hogs, and other livestock.
In summary, crotoxyphos is an insecticide used in the United States
for the control of external parasites on livestock, primarily cattle.
Small quantities of crotoxyphos are also used on hogs and other farm
animals. Of the quantities used on cattle, about 807. are used on dairy
I/ UVS. Department of Agriculture, Agricultural Statistics 1973, (1973).
2J U.S. Bureau of the Census, Census of Agriculture, 1969, Vol. V.,
Special Reports, Part 15, Graphic Summary (1973).
83
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Table 19. ESTIMATED PROPORTIONS OF CROTOXYPHOS CONSUMPTION FOR
DIFFERENT LIVESTOCK USES IN THE U.S. BY REGIONS, 1971
oo
•is
Type of livestock
Dairy
cattle
Beef
cattle
Hogs
Other
livestock3-'
Totals ,
all
livestock
Percent
Northeast!!/
North Central^/
Southeast!/
South Central®./
Northwest!/
Southwest^/
Total
19.5
47.6
7.9
12.0
5.1
7.9
100.0
2.9
57.1
2.9
14.3
11.4
11.4
100.0
7.7
76.9
7.7
7.7
negl.
negl.
100.0
16.7
16.7
16.7
16.7
16.7
16.7
100.0
16.0
50.1
7.0
12.3
6.2
8.4
100.0
Sources: U.S. Department of Agriculture, op. cit. (1974).
a/ Including poultry, sheep.
b/ New England States, New York, New Jersey, Pennsylvania.
£/ Ohio, Indiana, Illinois, Michigan, Wisconsin, Minnesota, Iowa, Missouri, North Dakota,
South Dakota, Nebraska, Kansas.
d/ Maryland, Deleware, Virginia, West Virginia, North Carolina, South Carolina, Georgia,
Florida.
e/ Kentucky, Tennessee, Arkansas, Louisiana, Mississippi, Alabama, Oklahoma, Texas.
fj Montana, Idaho, Wyoming, Colorado, Utah, Washington, Oregon, Alaska.
£/ New Mexico, Nevada, Arizona, California, Hawaii.
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cattle. In line with this use pattern, the largest quantities of
crotoxyphos geographically are used in the North Central region.
Crotoxyphos Uses in California - The State keeps detailed records
of pesticide uses by crops and commodities which are published quar-
terly and summarized annually. Table 20 summarizes the recorded uses
of crotoxyphos in California by individual uses for the 4-year period
1970 to 1973.
TABLE 20. CROTOXYPHOS USES IN CALIFORNIA BY CROPS
AND OTHER USES, 1970 - 1973
Year
Crop 1973 1972 1971 1970£'
Pounds of active ingredient
Cattle 3 - -
Other Miscellaneous
Uses 1539 7 2891
Total 1542 7 2891
Source: California Department of Agriculture, Pesticide Use
Reports for 1970, 1971, 1972 and 1973.
a/ No entry for crotoxyphos.
'In California, crotoxyphos is not subject to the special restric-
tions and reproting requirements imposed upon the sale and use of
pesticides designated as "restricted or injurious materials." For
this reason, the percentage of all crotoxyphos uses reported to the
State Department of Agriculture and included in its statistics is
not as high as in the case of restricted pesticides.
According to these state reports (Table 20), a total of 2,890 Ib
of crotoxyphos were used in California in 1971; 7 Ib in 1972; and
1,542 Ib in 1973. The 1970 California pesticide use report does not
contain any entries for crotoxyphos.
It appears that crotoxyphos usage on livestock is not significant
in California. However, it is possible that the system does not cover
livestock insecticides equally as well as pesticides used on crops.
85
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California officials concede that their pesticide reporting system
is least reliable in regard to pesticides whose use is not restricted
and which are applied by private individuals to their own crops or
animals. Crotoxyphos falls into this category.
In the light of these facts, it appears that the California data
summarized in Table 20 represents only a small fraction of the crotoxyphos
quantities that were actually used in the state in 1971, 1972, and 1973.
According to Table 19, an estimated 76,000 Ib crotoxyphos active ingre-
dient were used in the five Southwestern states in 1971. Taking into
account the cattle population in California as compared to that in New
Mexico, Nevada, Arizona, and Hawaii, MRI estimates that about half of
this quantity was used in California in 1971.
86
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References
Billings, S. C., ed., Pesticide Handbook—Entoma, 25th ed., Entomological
Society of America, College Park, Md. (1974).
California Department of Agriculture, Pesticide Use Reports for 1970, 1971,
1972 and 1973.
Frear, D. E. H., ed.. Pesticide Handbook - Entoma, 24th ed., College
Science Publishers, State College, Pa. (1972).
Lawless, E. W., R. von Rumker, and T. L. Ferguson, The Pollution Potential
in Pesticide Manufacturing. Pesticide Study Series - 5, Environmental
Protection Agency, Technical Studies Report: TS-00-72-04 (1972).
U.S. Bureau of the Census, Census of Agriculture, 1969, Vol. V., Special
Reports, Park 15, Graphic Summary (1973).
U.S. Bureau of the Census, U.S. Exports, Schedule B, Commodity by Country,
Report FT410.
U.S. Department of Agriculture, Agricultural Statistics. 1973, (1973).
U.S. Department of Agriculture, Fanners' Use of Pesticides in 1971 . . .
Quantities, Agricultural Economic Report No. 252, Economic Research
Service (1974).
U.S. Department of Agriculture, Quantities of Pesticides Used by Farmers
in 1964, Agricultural Economic Report No. 131, Economic Research Service
(1968).
U.S. Department of Agriculture, Quantities of Pesticides Used by Farmers
in 1966, Agricultural Economic Report No. 179, Economic Research Service
(1970).
U.S. Environmental Protection Agency, EPA Compendium of Registered
Pesticides, Vol. Ill, p. D 46, 1-D 46.3.
U.S. Tariff Commission, Imports of Benzenoid Chemicals and Products, 1972.
TC Publication 601 (1973).
U.S. Tariff Commission, Synthetic Organic Chemicals, U.S. Production
and Sales. TC Publication 681 (1971, 1972, 1973).
von Rumker, R., E. W. Lawless, and A. F. Meiners, "Production, Distribution,
Use and Environmental Impact Potential of Selected Pesticides," Contract
No. EQC - 311, for Council on Environmental Quality, Washington, D.C.
(1974).
87
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PART III. MINIECONOMIC REVIEW
CONTENTS
Page
Introduction 90
Efficacy Against Biting Flies Infestation 91
Horn Flies 91
Stable Flies 93
Face Flies 93
Cost Effectiveness of Biting Flies Control 94
Efficacy Against Cattle and Horse Tick Infestation 95
Cattle Tick 96
Lone Star Tick 96
Winter Tick 96
Horse Tick 97
Cattle Grub Control 97
Lice and Chorioptic Mange Mite Control 97
House Fly Control 97
References 99
89
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This section contains a general assessment of the efficacy and cost
effectiveness of crotoxyphos. Data on the production of crotoxyphos in
the United States as well as an analysis of its use patterns was conducted
as part of the Scientific Review (Part II) of this report. This section
summarizes rather than interprets data reviewed.
Introduction
Crotoxyphos is an organophosphate insecticide that is used primarily
for control of biting flies, ticks, and lice that attach to cattle. Its
effectiveness, economic benefits and cost often depend upon the method of
application, rate applied, and timing since contact with the animals may
be difficult to achieve because of their mobility. Various devices have
been developed to improve control of these insects. Back rubbers, dust
bags, movable and rigid sprays are a few devices which are commonly
used for application of crotoxyphos. The quanitity of insecticide
used will vary with the method of application.
The method of application is also important for control of different
insects. Some insects are controlled by only topside contact of the ani-
mal with the insecticide. Other insects are controlled by application
about the legs, face, or in the ears or nostrils of the cattle. The
way in which the insecticide protects the animal is also important to
the control. If it acts only as a repellant, a portion of the animal
may need to be contacted. If it acts on the larvae or adult insect, it
may have to be applied at the site of infestation.
A final variable affecting the efficacy (and economic benefit) is
the duration of control achieved. Control will vary with the type of
insect. For some, seasonal control can be achieved with one or two
applications. For other insects daily applications or periodic appli-
cations every 3 days or every week are necessary for good control.
Because of these variables, it is difficult to determine an overall
economic benefit of controlling a pest on a specific animal. This evalu-
ation is further complicated by the lack of data on the benefits of
insect control on animals. Control of flies and ticks is often referred
as good "herd management," and in many cases, it can prevent the spread
of disease which could disable or destroy the animal. This type of insect
control is a method of disease prevention; unfortunately, no data was
found regarding the economic value of the method.
90
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Limited data was available relating the use of crotoxyphos for
the control of flies to weight gain or milk production in cattle. Where
data was available, the economic benefits were determined by subtracting
the cost of the crotoxyphos from the additional income generated by the
increased weight gain or milk production. These benefits, based on 1972
cost data, are presented in dollars per animal per day or year.
Numerous articles were available on the efficacy of crotoxyphos on
a wide variety of pests. The pests considered in this review include
horn flies, stable flies and face flies on cattle; the southern cattle
tick, cattle tick, lone star tick, winter tick, and horse tick on cattle
and horses; the house fly in outdoor privies; and the rice weevil; confused
flour beetle; and the lesser grain beetle in stored rough rice.
Efficacy Against Biting Flies Infestation - Horn flies, stable flies, and
face flies are serious pests which attack cattle. Evidence is conflicting
concerning the effect of these pests on cattle weight or milk production,
but experimental tests have shown that under specific conditions gains in
weight and milk production have been experienced when biting flies were
controlled. Therefore, it has been considered as good herd management
practice to control flies on cattle.
Horn flies - Control of the horn fly has been relatively easy be-
cause of its unique parasitic habits which make possible its control
with only partial coverage of the animal.
The degree of control is dependent upon .the method of application
and the availability of the cattle for treatment. Various application
devices and methods have been developed. These include conventional
spray programs whereby animals are sprayed every 28 to 30 days through-
out the summer; the application of concentrated insecticides to cattle
in pastures or on rangeland through ultralow-volume aircraft or ground
devices; use of forced or free choice self-application devices; or feeding
of insecticide treated feed which kills the insects breeding in the
manure.
Crotoxyphos has been found to control horn flies in concentrations
as low as 0.125%. Hoffman et al. (1965)!/ evaluated various concen-
trations of crotoxyphos applied to cattle passing through a low volume
mist spray. They concluded that one application every 3 to 5 days would
be adequate to control these flies.
I/ Hoffman, R. A., J. L. Berry, and 0. H. Graham, "Control of Flies on
Cattle by Frequent, Low Volume Mist Spray Applications of Ciodrin,"
J. Econ. Entotnol.. 58:815-81? (1965).
91
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Eschle and Miller (1968)! evaluated crotoxyphos applied to ULV
sprayer at various Texas farms and achieved complete control of horn
flies with 2% crotoxyphos spray and nearly complete control with 0.5%
crotoxyphos spray. Costs ranged from 0.086c/animal/day for 2 ml/day of
0.5% ULV crotoxyphos to 4.4c/aniraal/day for 2 oz/day of 2% crotoxyphos
applied as a mist spray. The savings for the ULV application was 98%
over the mist spray.
Horn flies can also be controlled with dust bags. Poindexter and
Adkins (1970)2/ achieved 85% control when cattle had access to dust bags
containing 3% crotoxyphos. They concluded that this method would be
effective if the bags are frequently contacted by the cattle and they
are maintained with dust. Similar results were found by Knapp (1972) .$/
Control varied from 81 to 99% for the season with 3% crotoxyphos. The
difference in efficacy was attributed to the type of cattle, the location
and use of the duster.
Back rubbers are commonly used for control of the horn fly. Dorsey
et al. (1966)A/ evaluated back rubbers for control of horn flies and found
that a 0.757. crotoxyphos back oiler gave a 95% reduction of horn flies
in tests in 1962.
I/ Eschle, J. L., and A. Miller, "Ultra-Low Volume Application of Insecti-
cides to Cattle for Control of the Horn Fly," J. Econ. Entomol..
61:1617-1621 (1968).
21 Poindexter, C. E., and T. R. Adkins, Jr., "Control of the Face Fly
and the Horn Fly with Self-Applicatory Dust Bags," J. Econ. Entomol.,
63:946-948 (1970).
V Knapp, F. W., "Evaluation of Dust Bags for Horn Fly Control on Cattle,"
J. Econ. Entomol.. 65:470-472 (1972).
4/ Dorsey, C. K., J. 0. Heishmann and C. J. Cunningham, "Face Fly and Horn
Fly Control on Cattle—1962-1964," J. Econ. Entomol.. 59:726-732
(1966).
92
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Stable flies - The stable fly is a serious pest of cattle during
the summer months because of its bloodsucking deeding habits. Experimental
results have shown that stable flies can cause a reduction in milk produc-
tion in dairy cows (Bruce and Decker, 1958)i/.
Crotoxyphos has been used successfully to control the stable fly.
Harris (1964)^.' found that crotoxyphos was much more toxic to stable flies
than chlorinated hydrocarbons.. The LDso value expressed as micrograms
of insecticide per gram of fly weight was 1.04 for crotoxyphos, compared
to 3.89 and 9.69 for two other pesticides tested.
Mount et al. (1953)—' found that crotoxyphos at 4 to 6 ppm resulted
in 100% mortality of stable fly larvae. Against the adult flies, 98 to
100% mortality was achieved with concentration of 0.05 to 0.25%.
Hoffman et al. (1965) evaluated various concentrations of crotoxy-
phos applied to cattle passing through a low volume mist sprayer. Stable
tiles were killed when contacted by the spray, but no residual effectiveness
was observed. Campbell and Hermanussen (1971)A/ applied 2 qt of 0.5%
crotoxyphos to the legs and lower body of cows and achieved an 85% reduc-
tion in flies after 1 day. However, this reduction dropped to 50% in 4
days and flies had increased to the same level as on untreated cows at the
end of 7 days.
Face flies - The face fly, has become an increasing cattle pest
problem in the past two decades. It has been reported as a cause of cattle
annoyance and eye disorders (Dobson and Huber, 1961) .H/ Crotoxyphos is
used for control of the face fly.
I/ Bruce, W. N., and G. C. Decker, "The Relationships of Stable Fly
Abundance to Milk Production by Selected and Randomized Dairy Herds,"
J. Econ. Entomol.. 51:269-274 (1958).
2/ Harris, R. L., "Laboratory Tests to Determine Susceptibility of Adult
Horn Fly and Stable Fly to Insecticides," J. Econ. Entomol.. 57:492-
494 (1964).
3/ Mount, G. .A., J. B. Gahan, and C. S. Lofgren, "Evaluation of Insecti-
cides in the Laboratory Against Adult and Larvae Stable Flies,"
J. Econ. Entomol.. 58:685-687 (1965).
4/ Campbell, J. B., and J. F. Hermanussen, "Efficacy of Insecticides and
Methods of Insecticidal Application for Control of Stable Flies in
Nebraska." J. Econ. Entomol.. 64:1188-1190 (1971).
J5/ Dobson, R. C., and D. A. Huber, "Control of Face Flies (Musca autumnalis)
on Beef Cattle in Indiana," J. Econ. Entomol.. 54:434-436 (1961).
93
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Granett et al. (1962)!/ evaluated several insecticides for control
of the face fly and found that crotoxyphos controlled 59 to 60% of the
flies 24 hr after 1 pint of 0.5% active ingredient was applied to cattle.
One pint of 1.0% active ingredient gave 75% control after 24 hr.
Hair and Adkins (1965)A/ found that a 1% crotoxyphos back rubber
formulation gave 85% control of face flies during the season. However,
Doresey et al. (1966) found seasonal face fly control with crotoxyphos
varied from 11% to 64%. A 0.75% formulation on a back rubber provided
14% control while a 5% dust applied at 2 oz/head/week gave 64% control.
In another test, dust bags containing 3% crotoxyphos gave 11% seasonal
control. Poindexter and Adkins (1970) achieved a 43% control of the
face fly on cattle exposed to 3% crotoxyphos dust bags.
Cost Effectiveness of Biting Flies Control - The economic benefits from
controlling biting flies with crotoxyphos should be measurable in terms
of weight gain for beef cattle or increased milk production from dairy
cows. The results of several tests show that, under certain conditions,
increased weight or milk production can be achieved.
Several tests have been conducted to determine the effect of flies
on dairy cow milk production. Bruce and Ducker (1958) estimated from
regression analysis that average rates of loss were 0.65% for butterfat
and 0.7% for milk production per stable fly per cow and that these
losses extended beyond the fly season. Cheng and Kessler (1961)A'
evaluated milk production and fly control over a 3-year period and con-
cluded that herds that are well managed and liberally supplied with
supplementary feeds will not have any significant loss of milk production
when face, horn, and stable flies are present. Average daily milk pro-
duction in these herds varied from a loss of 5.0 Ib/day to gain 1.1 lb/
day when herds were treated to control flies.
I/ Granett, P., E. J. Hansens, and A. J. Forgash, "Tests Against Face
Flies on Cattle in New Jersey During 1961," J. Econ. Entomol.,
55:655-659 (1962).
2l Hair, J. A., and T. R. Adkins, Jr., "Dusting Stations and Cable Back
Rubbers as Self-Applicatory Devices for Control of the Face Fly,"
J. Econ. Entomol., 58:39-41 (1965).
3f Cheng, T. H., and E. M. Kessler, "A Three-Year Study on the Effect of
Fly Control and Milk Production by Selected and Randomized Dairy
Herds." J. Econ. Entomol.. 54:751-757 (1961).
94
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Miller et al. (1973)i/ evaluated the effect of stable flies on milk
production and concluded that they did not have a significant adverse
effect on milk production. Milk production varied from a loss of 2.7 lb/
day to a gain of 2.3 Ib/day when the cows were exposed to the flies.
The results of these tests indicate that fly control of dairy cattle
can produce changes in milk production ranging from a gain of 2.3 Ib/day
to a loss of 5.0 Ib/day. At a milk price of $6.07/cwt in 1972, (Agri-
cultural Statistics. 1973JL/ the additional income would range from a
loss of $0.30 to a gain of $0.14/cow/day from the use of crotoxyphos to
control flies.
The cost of the application will vary with the method used. Eschle
and Miller (1968) estimated the cost of control per cow with crotoxyphos
in tests conducted in 1967, ranged from 0.086
-------
Cattle tick - The cattle tick and the Southern cattle tick, once
serious pests to agriculture in the. U.S., have been eliminated as problems
to domestic industry (Drummond et al., 1973).I/ However, imported cattle,
particularly from Mexico, still remain a problem and must be treated.
Treatment is most often performed at border stations.
Drummond et al. (1968)2/ found that crotoxyphos sprayed on cattle in
concentrations of 0.15 and 0.30% gave 99.5 to 100% control of both ticks.
Drummond et al. (1972)!' conducted similar tests and obtained 99.8% con-
trol of the cattle tick with 0.075% crotoxyphos and 93.2% control of the
Southern cattle tick. He concluded that 99% control of the cattle tick
could be achieved with 0.075% crotoxyphos and 99% control of the Southern
cattle tick could be achieved with 0.15% crotoxyphos.
Lone Star tick - The lone star tick infests horses and cattle in the
spring and early summer. Drummond and Medley (1965)A7 compared various
insecticides for control of this pest in Texas. Crotoxyphos at concentra-
tions varying from 0.1 to 0.75% gave 80 to 99% control 1 day after appli-
cation. At the end of 1 week, control at concentrations of 0.25 to 0.75%
was 84 to 88%; by the end of 3 weeks, little or no control was experienced.
Similar results were obtained by Drummond et al. (1967)1.' when 0.3%
crotoxyphos gave 95% control after 1 day and 5% after 3 weeks.
Winter tick - The winter tick is found in the Northern United States,
in the Western states and Texas. It can be a serious pest to cattle and
horses. Drummond and Medley (1965) found that 0.25% crotoxyphos sprayed
on cattle gave complete control of winter ticks 1 month after treatment.
Complete control of the winter tick was also achieved on horses 1 month
after a spray treatment of 0.3% crotoxyphos.
if Drummond, R. 0., S. E. Ernst, J. L. Trevino, W. J. Gladney, and 0. H.
Graham, "Boophilus annulatus and ]J. microplus; Laboratory Tests of
Insecticides for Control on Cattle," J. Econ. Entomol., 66:130-133
(1973).
2J Drummond, R. 0., S. E. Ernst, J. L. Trevino, and 0. H. Graham, "Insecti-
cides for Control of the Cattle Tick and the Southern Cattle Tick on
Cattle," J. Eeon. Entomol., 61:467-470 (1968).
3/ Drummond, R. 0., S. E. Ernst, J. L. Trevino, W. J. Gladney, and 0. H.
Graham, "Boophilus annulatus and B^. microplus: Sprays and Dips of
Insecticides for Control on Cattle," J. Econ. Entomol., 65:1354-
1357 (1972).
4/ Drummond, R. 0., and J. G. Medley, "Field Tests with Insecticides for
Control of Ticks on Livestock," J. Econ. Entomol., 58:1131-1136 (1965).
57 Drummond, R. 0., T. M. Whetstone,and S. E. Ernst, "Control of the Lone
Star Tick on Cattle," J. Econ. Entomol., 60:1735-1738 (1967).
96
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Horse tick - The tropical horse tick is limited to Texas, Georgia,
and Florida. It is of veterinary importance in Florida because it trans-
mits equine pirqplasmosis (Drummond et al., 1971b).±J Drummond and
Ossorio (1966)—' found that 0.3% crotoxyphos in cottonseed oil or water
or a 5% crotoxyphos dust were highly effective in killing the horse tick
at all stages of development. The applications were made in the ears and
false nostrils of the horses. Drummond et al. (1971b) evaluated several
insecticides for toxicity to the horse tick.
Cattle Grub Control
The cattle grub causes economic loss to cattle through additional
trim losses-on beef carcases (Rich 1970).—' Grubs are also thought to
have an effect on milk production. Knapp (1972b)A/ found that lactating
dairy cows sprayed twice daily with 2% crotoxyphos oil during the active
period of the adult heel fly reduced the cattle grub from 74 to 96% in a
series of tests. Since crotoxyphos is not a systemic insecticide it was
postulated that the control was due to the crotoxyphos acting either as
an ovicide or a repellent to the adult heel fly, or that the crotoxyphos
residue killed the larvae.
Lice and Chorioptic Mange Mite Control
Dairy cattle are affected by various types of lice. Some of these
are the cattle biting lice, long-nosed cattle louse, short-nosed cattle
louse, and the little blue louse. Matthysse et al. (1967)A/ evaluated
crotoxyphos for control of lice and mange mites. Crotoxyphos was sprayed
on dairy cows with either a low or high volume spray. They found that
two applications of 0.25% crotoxyphos resulted in elimination of lice 6
weeks after the second spraying. It was completely effective against all
species of lice. In a later test, two applications of 2% crotoxyphos at
8 oz/cow eradicated lice and chorioptic mange mites.
House Fly Control
The common house fly is also prevalent around poultry, cattle, and
outdoor privies. Crotoxyphos has been evaluated for toxicity and control
of the house fly.
\J Drummond, R. 0., W. J. Gladney, T. M. Whetstone, and S. E. Ernst,
"Testing of Insecticides Against the Tropical Horse Tick in the
Laboratory," J. Econ. Entomol., 64:1164-1166 (1971b).
2j Drummond, R. 0., and J. M. Ossorio, "Additional Tests with Insecticides
for Control of the Tropical Horse Tick on Horses in Florida," £.
Econ. Entomol., 59:107-110 (1966).
3J Rich, G. B., "The Economic Systemic Insecticides Treatment for Reduc-
tion of Slaughter Trim Loss Caused by Cattle Grubs, Hypoderma Spp.,"
Canadian Journal of Animal Science. 50:301-310 (1970).
kl Knapp, F. W., "Prevention of Cattle Grub Infestation in Lactating
Dairy Cows by Use of Daily Applications of Crotoxyphos," J. Econ.
Entomol., 65:466-467 (1972b).
5/ Matthysse, J. G., R. F. Pendleton, A. Padula, and G. R. Nielson,
"Controlling Lice and Chorioptic Mange Mites on Dairy Cattle,"
'J. Econ. Entomol.. 60:1615-1622 (1967).
97
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Georghiou (1967)!/ evaluated the susceptibility and resistance of
house flies to insecticides and reported that resistance to organophos-
phates was increasing in the.house fly. Labrecque et al. (1966)^7
evaluated crotoxyphos for control of flies in outdoor privies on Grand
Turk Island in the British West Indies. A 1.0% crotoxyphos in diesel
oil sprayed at 100 to 200 mg/ft2 in the pits of the privies gave up to
3 days of 100% control. The authors indicated that the diminishing
number of outdoor privies in the United States has relegated the problem
of house fly control in this environment to a minor role. However, they
note that this problem is still urgent in many countries.
I/ Georghiou, G. P., "Differential Susceptibility and Resistance to
Insecticides of Coexisting Populations of Musca domestica, Fannia
canicularis, F^. femoralis, and Ophryra leucostoma," J. Econ.
Entomol.. 60:1338-1344 (1967).
2J Labrecque, G. C., M. C. Evers, and D. W. Meifert, "Control of House
Flies in Outdoor Privies with Larvicides," J. Econ. Entomol.,
59:245 (1966).
98
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References
Agricultural Statistics. 1973, U.S. Department of Agriculture (1973).
Bruce, W. N., and G. C. Decker, "The Relationships of Stable Fly Abundance
to Milk Production by Selected and Randomized Dairy Herds," J. Econ.
Entomol.. 51:269-274 (1958).
Campbell, J. B., and J. F. Hermanussen, "Efficacy of Insecticides and
Methods of Insecticidal Application for Control of Stable Flies in
Nebraska." J. Econ. Entomol.. 64:1188-1190 (1971).
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