SUBSTITUTE CHEMICAL PROGRAM
INITIAL SCIENTIFIC
MINIECONOMIC REVIEW
CAPTAN
APRIL 1975
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
CRITERIA AND EVALUATION DIVISION
WASHINGTON, D.C. 20460
r
EPA-540/1-75-012
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For sale by National Technical Information Service
Springfield, Va. 22151
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SUBSTITUTE CHEMICAL PROGRAM
INITIAL SCIENTIFIC
AND
MINIECONOMIC REVIEW
OF
CAPTAN
APRIL 1975
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
CRITERIA AND EVALUATION DIVISION
WASHINGTON, D.C. 20460
EPA-540/1-75-012
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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. Its contents do not
necessarily reflect the views and policies
of the Environmental Protection Agency,
nor does mention of trade names or commer-
cial products 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 may be more deleterious to man and his envi-
ronment, than a problem pesticide (one that has been suspended, cancelled,
deregistered or in an "internal review" for suspected "unreasonable,
adverse effects to man or his environment"). The major objective of the
program is to determine the suitability of 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 cost 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
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.
This report contains the Phase I Initial Scientific and Minieconomic
Review of Captan [N-(trichloromethylio)-4-cyclohexene-l,2-dicarboximide].
Captan was identified as a registered substitute chemical for certain
problematic uses of the ethylenebisdithiocarbamate (EBDC) fungicides which
are under internal EPA review for suspected adverse effects. Where
applicable, the review also identifies areas where technical data may be
lacking so that appropriate studies may be initiated to develop desirable
information.
iii
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The review covers all uses of captan and is intended to be adaptable
to future needs. Should captan be identified as a substitute for a problem
pesticide other than EBDC fungicides, the review can be updated and made
readily available for use. The data contained in this report was not
intended to be complete in all areas. Data-searches ended in January,
1975. This 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 direc-
tion and technically review information retrieved during the course of
the study. The following EPA scientists were members of the review
team: Eugene Pelletier, Ph.D. (Registered Uses), team leader; Padma
Datta, Ph.D. (Chemistry); William Burnam (Pharmacology and Toxicology);
John Bowser (Fate and Significance in the Environment); Howard Kerby, Ph.D.
(Fate and Significance in the Environment); Jeff Conopask (Economics).
Data research, abstracting and collection were primarily performed
by Midwest Research Institute, Kansas City, Missouri (EPA Contract #68-
01-2448). RvR Consultants, Shawnee Mission, Kansas, under a subcontract
to Midwest Research, assisted in data collection. Stauffer Chemical
Company and Chevron Chemical Company, manufacturers of captan, made
certain comments and additions to this report. The recommendations of
the following National Environmental Research Centers, EPA Office of
Research and Development have also been incorporated: Gulf Breeze
Environmental Research Laboratory, Gulf Breeze, Florida; National
Water Quality Laboratory, Duluth, Minnesota; Southeast Environmental
Research Laboratory, Athens, Georgia.
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 41
Subpart C. Fate and Significance in the Environment . . 88
Subpart D. Production and Use 122
Part III. Minieconomic Review 161
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FIGURES
No. Page
1 Production and Waste Schematic for Captan 14
2 General Scheme for Multiple Residues 21
3 Analytical Scheme for Chlorinated (Non-Ionic) and
Organophosphate Residues 22
4 Metabolic Pathway for Captan-1^C=0 in the Rat 58
VI
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TABLES
No. Page
1 Raw Materials and By-Products in the Manufacture
of Captan 16
2 U.S. Tolerances for Captan on Raw Agricultural
Commodities 35
3 The Toxicity of Captan - Rats 44
4 Toxicity Data on Captan - Laboratory Animals 47
5 Summary of Oral Toxicity Data for Captan - Domestic
Animals 50
6 Histopathological Observations on Rats Administered
Captan 54
7 Results of Captan and Thalidomide Administration to
Pregnant Monkeys 63
8 Teratogenic Activity of Thalidomide, Captan and
Captan Metabolites in Rabbits 64
9 Teratogenic Activity of Captan in Hamsters 67
10 Teratogenic Activity of Captan in Rats 69
11 Summary of Teratogenic Investigations with Captan 71
12 Summary of Mutagenic Investigations with Captan 79
13 Toxicity of Captan to Fish 90
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TABLES (Continued)
No. Page
14 Toxicity of Captan: 96-hr TL5Q and LTC for Three
Species of Fish
92
15 Toxicity of Captan to Fish in Standard Reconstituted
Static Water 93
16 Toxicity of Captan to Fish in City Filtered Water at
12°C (Flow-Through System) ..... 94
17 Survival and Growth of Fathead Minnows During Chronic
Exposure Tests 95
18 Species of Fish Used in Toxicity Tests with Captan ... 97
19 Summary of Registered Uses of Captan 124
20 Registered Uses of Captan 50% Wettable Powder—Crops and
Other Uses, Diseases Controlled Dosage Rates, and Use
Limitations 141
21 Farm Uses of Captan in the U.S. in 1964, 1966, 1971,
and 1972 150
22 Estimated Farm Uses of Captan in the U.S. by Regions
and Major Crops (1972) 152
23 Captan Uses in California by Major Crops and Other
Uses (1970-1973) 155
24 Use of Captan in California in 1972, by Crops, Applica-
tions, Quantities, and Acres Treated 156
Vlll
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TABLES (Continued)
No. Page
25 Use of Captan in California in 1973, by Crops, Applica-
tions, Quantities, Acres Treated 158
26 Yield (Bushels/Tree) from Captan (Orthocide SOW) Sprayed
Apple Trees 165
27 Yield and Profits from Using Orthocide SOW in Selected
States 166
28 Results of Captan Application on Strawberries 168
29 Yield Results (Quarts/Acre) and Profits for Five Applica-
tions of Captan to Strawberry Plants 169
30 Results of Captan Application to Potato Seed Pieces . . . 170
IX
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PART I. SUMMARY
CONTENTS
Production and Use
Toxicity and Physiological Effects
Food Tolerances and Acceptable Intake
Environmental Effects
Page
Limitations in Available Scientific Data 10
Efficacy and Cost Effectiveness 10
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This subsection contains a brief summary of the Initial Scientific
and Minieconomic Review conducted on captan. The section summarizes rather
than interprets scientific data reviewed.
Production and Use
Captan [N-(trichloromethylthio)-4-cyclohexene-l,2-dicarboximide] is
a contact fungicide effective against a fairly broad spectrum of plant
pathogenic fungi. It is estimated that about 17 million pounds of captan
were produced in the United States in 1972 by the only major domestic
manufacturer, Calhio Chemicals, Inc., a jointly owned subsidiary of
Stauffer Chemical Company and Chevron Chemical Company. The production
plant is located in Perry, Ohio.
Captan is manufactured in a two-step synthesis, followed by several
purification steps:
NH + NaOH > | N-Na + H20 (1)
4- C1SCC13
on
Captan
Available literature on the chemistry of captan focuses primarily
degradation reactions. Captan is reported to be decomposed by hydroly-
sis (essentially complete hydrolysis of a 2% slurry at 100° C in 2-1/2
thermal decomposition; and photolysis. r^
Captan is available to users in the United States in a great va '
of dry formulations, i.e., wettable powders, dusts, and as a 4.0 lb/ i ^
aqueous suspension.
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In addition to the products that contain captan as the only active in-
gredient, a number of formulations (dusts and granulars) are available
containing captan in combination with other fungicides and/or insecticides
for foliar application and seed treatment. The 50 and 80% wettable
powders and 7.5 to 15% dusts that contain captan alone as an active
ingredient are apparently the most widely used formulations.
An estimated 16 million pounds of captan were used in the United
States in 1972—about 10 to 15 million pounds in agriculture and 1 million
by home gardeners. Regional consumption of the captan used for agriculture
in 1972 is estimated as follows: Northeastern states—3.5 million pounds
(primarily on apples, other deciduous fruits, and small fruits);
Southeastern states—2.0 million pounds; North Central states—2.0
million pounds; Northwestern states—1.7 million pounds; South Central
states—500,000 pounds; and Southwestern states—300,000 pounds. The
use of captan on fruit and nut crops is estimated to account for about
9 million pounds in 1972, i.e., 90% of all the captan used in agricul-
ture.
Toxicity and Physiological Effects
Toxicity - Limited data were found on the acute and subacute toxicity,
inhalation effects, or the possible occupational hazards (in manufacture
or application) of captan on man. In a study of chromosomal aberrations
among workers in a captan formulating plant, no chromosomal damage was
reported. Captan is considered to be a mild sensitizer.
The LD5Q of captan in rats ranges from approximately 8,400 to
12,000 mg/kg of body weight. The chronic oral LD5Q (100 days) for
rats is 916 t 233 mg/kg body weight per day. Mice have received 560
ppm in the diet for 18 months without any lethal toxic effects.
The "no effect" level of captan for dogs is 100 mg/kg/day (duration
of test not specified). Swine have consumed 4,000 ppm of captan over a
175-day period without any toxoic symptoms. In an analysis of pesticide
residues in food, the Food and Agricultural Organization/World Health
Organization (FAO/WHO) in 1970 reported 12.5 mg/kg as the dose producing
no adverse effects for monkeys, after eleven days of dosing.
Cattle and sheep seem to be selectively sensitive to captan: six
doses of 250 mg/kg/day caused death in cattle, and sheep have been
poisoned by single doses of 250 mg/kg or higher.
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Metabolism - Captan is rapidly absorbed from the gastrointestinal tract
and is rapidly destroyed in the blood. It does not accumulate in the
tissues of pigs or chickens. Captan reacts readily with cysteine,
glutathione and other compounds containing SH groups.
Until recently the major metabolic products of captan were con-
sidered to be tetrahydrophthalimide (THPI), chloride ion, thiophosgene,
carbonyl sulfide, hydrogen sulfide and a substituted thiazolidinethione.
Investigators have now found THPI to be further metabolized to 3-OHTHPI,
3-OH-tetrahydrophthalamic acid, THPI-epoxide and 4,5-di-OH-THPI.
Captan induces mitochondrial swelling by two mechanisms, one of
which is energy dependent.
Reproduction - Up to 1,000 ppm of captan was fed to two generations
of rats (two litters per generation) without any effect on fertility,
gestation, viability or lactation indices. In the third generation,
the lactation index was suppressed slightly. When captan was given
in daily doses of 6 to 57 mg/kg, sperm motility was decreased in rats.
The same observation was made for mice (daily dosage 20 to 25 mg/kg).
In another test, mice received 50 or 100 mg/kg for 5 days. The fertility
index was depressed at the 100 mg/kg level. The weaning weights were
decreased in the first litter of the second generation.
Teratology - Single and multiple doses (200 to 1,000 mg/kg) of captan
have been given to pregnant hamsters on the 7th and 8th day and on
days 6 to 10 of gestation. Anomalies occurred after single-dose
administration. A dose level of 750 mg/kg given on day 7 resulted
in 13.7% deformed young and 22% mortality among the dams. When a
dose of 500 mg/kg was given on days 6 to 10 of gestation, the young
were normal. At higher levels fetal death and small fetuses were
observed, but there were no anomalies.
In another test, hamsters were given 125, 250 and 1,000 mg/kg of
captan each day for the first 15 days of gestation. There were no
more terata in the test group that received 1,000 mg/kg than in the
control group.
Results of studies on rabbits arc contradictory. In two studies,
levels of 80 and 75 mg/kg during gestation (7 through 12 days and 6
through 16 days , respectively) produced no malformed fetuses. Conversely,
nine malformed fetuses were found in 75 implants in nine pregnant rabbits
in another study. In a further investigation, high levels of captan
(50 to 2,000 mg/kg body weight) did not produce a significant increase
in the number of abnormalities (371 fetuses were observed)
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No teratogenic effects were observed in monkeys receiving daily
doses of 6.25, 12.5 or 25 mg/kg of captan. Fetal mortality was high at
the 25 mg/kg level.
An incidence of 7 to 8% malformations has been observed in chick
embryos where the eggs were injected with 3 to 20 ppm of captan. Feeding
studies resulted in no terata.
In tissue cultures (human embryonic cells), 4 mg/ml of captan
severely inhibited growth for 48 hr. After that period the cells re-
covered and normal growth ensued.
Mutagenesis - A number of investigations have been made of mutagenic
effects of captan. Mutations have been observed in microorganisms,
Escherichia coli, Salmonella typhimurium, Neurospora crassa»Saccharomyces
cerevisiae. Two hundred fifty micrograms per assay disk of captan in
contact with Escherichia coli produced a sixfold increase in mutants; a
tenfold increase was produced by 1,000 p-g/assay disk.
Captan produced positive evidence of mutagenesis in the forward
mutation system and none in the reverse mutation system using Neurospora
crassa as a test organism.
In one investigation with Saccharomyces cerevisiae, captan was
found to be a weak agent for mitotic gene conversion and did not induce
cytoplasmic mutation.
In tests using Escherichia coli B/r ochre auxotrophic mutant,
captan has produced marked mutagenic activity by causing an approxi-
mate 20-fold increase in numbers of revertents in the excision repair defi-
cient strain and approximately 100-fold increase in the excision repair
competent strain.
It has been shown in E. coli strains that a substantial part of the
mutagenic activity of captan is due to excisable DNA damage mediated by
a volatile breakdown product.
In one investigation, captan did not bring about sex-linked reces-
sive lethal mutations, translocations, or dominant lethal mutations in
Drosophila melanogaster. Another investigation reported that captan was
not mutagenic (sex-linked recessive lethal test) in Drosophila melanogaster.
It was concluded that captan was inactivated before it could reach the germ
cells.
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Chromosome studies were made of a heteroploid human embryonic cell
line exposed to captan. An increase in breaks was noted 24 hr after the
addition of captan. The breaks persisted for 24 hr. The breaks were
mostly chromatid type. In a kangaroo rat cell line, the percentage of
chromosome breaks rose from 10% at 1 u.g/ml to 70% at 10 u.g/ml of captan.
Captan did not produce dominant lethal mutations when mice were in-
jected intraperitoneally (single) with 3.5 and 7.0 mg/kg of captan. In
other investigations with mice, the incidence of dominant lethal muta-
tions was in the normal range.
In another experiment, at the highest dose levels of intraperitoneally
(10 mg/kg) or orally (200 mg/kg) administered captan, no dominant lethal
mutants were indicated; there were no decreases in total implantations
per pregnant female.
Oncogenesis - It was shown that captan injected intraperitoneally
(0.15 g/kg for 14 days) increased the mean survival times of mice
(26 to 80 days) inoculated with ascites tumor cells 1 day prior to captan
treatment. All mice treated with captan developed solid masses at the
site of injection into the abdominal wall; no histological evaluations
of the masses were made.
Captan has been administered to mice at a level equivalent to about
560 ppm in the diet for 18 months? there was no significant increase
of tumors over the controls.
Food Tolerances and Acceptable Intake
Tolerances for captan residues have been established in the United
States on 67 raw agricultural commodities. These tolerances range from
2 to 100 ppm. Ten of these 67 tolerances are currently designated as
interim. Captan tolerances established by the World Health Organization
range from 5 to 40 ppm.
Captan has not been reported as a significant residue in any food
crops. Captan residues are detected only occasionally in samples from
FDA total diet studies, and analytical tests specifically for captan
are not ordinarily performed.
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The acceptable daily intake (ADI) for captan was set at the 1965
joint meeting of the FAO Committee on Pesticides in Agriculture and the
WHO Expert Committee on Pesticide Residues. The ADI for captan is
0.125 mg/kg.
Environmental Effects
The toxicity of captan to fish has been studied in some detail.
The effects of captan on other aquatic species, however, have not been
as thoroughly examined. Available acute toxicity data for captan to
fish are summarized as follows:
Specie
Toxicity
calculation
Toxicity
measured
Fathead minnows 3.5 Months TI^ (96 hr) 65 ygM
Fathead minnows Fingerlings LC5Q (96 hr) 120 yg/£
Bluegills
Bluegills
Brook trout
Zebrafish
Carp
Goldfish
Rainbow trout
Coho salmon
Lake trout Fingerlings LC5Q (96 hr) 51.0
Channel catfish Fingerlings LC5Q (96 hr) 77.5 Vg/H
Lake trout Fingerlings LCso (96 hr) 75.2 yg/£
Cutthroat trout Fingerlings LC5Q (96 hr) 48.5 yg/fc
1.5 Months TLju (96 hr) 72 yg/£
Fingerlings LC5Q (96 hr) 150 yg/£
1.5 Months TLjj, (96 hr) 34 yg/£
Larvae LC50 (90 min) 0.67 ppm
Young TLm (48 hr) 0.25 ppm
Young TLm (48 hr) 0.037 ppm
Fingerlings LC$Q (96 hr) 102 yg/fc
Fingerlings LC^Q (96 hr) 56.5
System
Flow-through
Flow-through
Static
Static
Flow-through.
Flow-through
Static
Static
Static
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LC5Q values for captan in the food of mallard ducks, pheasants
Japanese quail, and bobwhite quail (all 2 weeks old) were found to
be > 5,000, > 5,000, > 5,000, and > 2,400 ppm, respectively.
Captan is not toxic to red-wing blackbirds and starlings at a single
oral dose of 100 mg/kg.
The observations of numerous investigators indicate that captan,
at fungicidally effective rates of application, appears to be relatively
harmless to beneficial insects (predators and parasites) occurring in
deciduous fruit orchards. The review included reports of investigation
on the following: Predatory mites (Thyplodromus sp., Amblyseius
fallacis, and Agistemus fleschneri), European red mite (Panonychus ulmi),
larvae of the aphid lion (Chrysopa carnea), parasitic wasps (Trichogramma
sp., Mormoniella vitripennis, and Aphelinus mali), and predatory bugs
(Anthocoris nemorum and Orius sp.). Among all of the accounts reviewed,
only one reported "some mortality" to the predatory bug Orius sp., and to
the parasitic wasp Aphelinus mali. Captan is considered relatively
non-toxic to honey bees.
The data reviewed indicates that captan affects a number of soil
bacteria and fungi. In tests where captan was applied to cultures of
the predominant microfungi of cattail marsh (Hansenula saturnus, Mucor
hiemalis, Penicillium stipitatum, and Trichoderma viride), all four
fungi were inhibited. However, subsequent application of captan to
field plots in a cattail marsh did not reduce the number of micro fungal
propagules in the litter, water or mud.
Field and greenhouse trials showed thatcaptan, at the concentration
of 250 ppm, stimulated the soil bacteria in loam soil for about 12 weeks.
Actinomycetes were least affected, while most of the physiological groups
of the soil bacteria, such as nitrogen-fixing organisms, cellulose de-
composers, spore-forming bacteria, and denitrifying bacteria, were
stimulated. In some instances, the addition of captan resulted in a
decrease in the nitrifying bacteria, ammonifying forms, anaerobic bac-
teria, and soil algae. Azotobacter chroococcum was significantly in-
hibited for several weeks. Many soil fungi, including Penicillium,
Aspergillus, Trichoderma, Cephalosporium, Hyalopus, Acrostalagmus,
Verticillium,, Aleurisma, Sporotrichum, Strachybotrys. Phymatotrichum,
Phoma, Spicaria, Hormodendrum, Claddsporium, jicopulariopsiE.. Oospora and
Fusarium were markedly reduced.
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Few reports were found on the toxicity of captan to the lower ter-
restrial fauna. One review report and several studies on earthworms
indicate that captan is relatively nontoxic to such organisms.
Data on the residues of captan in the natural soil indicate that
captan appears to be rapidly degraded. Captan is believed to be de-
gradable by biological as well as by chemical mechanisms. When captan
is uniformly distributed in the soil, its half-life ranges from 1 to 2
weeks to only 1 to 2 days, depending on a number of environmental
factors. When applied to the soil at localized higher concentrations
(e.g., seed protectant use), captan residues persist longer in those
specific locales. Degradation in a loam soil is reported to be 99%
in seven days.
There were no reports found on the presence (or absence) of
captan in water, air, or nontarget plants.
A recent study of the bioaccumulation and biomagnification of cap-
tan using a terrestrial-aquatic model ecosystem showed that none of the
test organisms contained any captan residues at the end of a 33-day test.
The investigators concluded that captan does not persist in water, and
that "it appears that continued use of captan will not have any serious
environmental impact, as it does not persist in the water of this 33-
day model ecosystem, nor does it accumulate in the fish which is the
upper member of the food chain."
Available data indicates that captan is rapidly degraded by chemical
as well as by biological mechanisms. Captan has been rated using an
index designed to determine the propensity of pesticides for volatilization
and leaching under simulated field conditions for loam soils at 25° C
and an annual rainfall of 59 in. By this method, captan rated a volatili-
zation index of 2, indicating an estimated median vapor loss from treated
areas of 1.8 Ib/acre/year. This index number indicates that the propensity
for volatilization of captan from treated fields is in the intermediate
range, compared to other pesticides. Captan rated a leaching index
number of 1, indicating movement of less than 4 in. through the soil.
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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. LDcQ values for intravenous, subcutaneous, and intraperitoneal
injection in various species.
2. Inhalation toxicity. Studies should be conducted on application
rates, modes of spray application and spraying conditions to
the inhalation exposure experienced by workers.
3. Laboratory and field studies on effects on lower aquatic
organisms.
4. Residues in water and air.
Efficacy and Cost Effectiveness
The economic benefits of using captan have been determined from
field tests for control of scab and rot on apples; brown rot and scab
on peaches; gray mold of strawberries, potato scab on potatoes; and
seedling diseases of soybeans. However, the data is incomplete and
should be looked upon with caution.
Captan is a good all-around fungicide for control of scab and
rots on apples. Although several tests have been reported in which
yields of captan treated trees were measured, none compared to the
test results untreated trees. Since apple crops are greatly reduced
when no fungicide is used, the yields from these trees were used as
a direct measure in estimating economic benefits.
Captan also controls brown rot and improves the finish of ripened
peaches. The results of one set of tests showed a 42 Ib/tree increased
yield due to the use of captan. This resulted in an economic benefit of
$2.60/tree.
Potato seeds treated with captan for potato scab have shown yield
increases ranging from 15 to 58 cwt/acre. The resultant economic bene-
fits varied from $35.60 to $142.50/acre.
Soybean seedlings treated with captan resulted in a 3.7 bushel yield
increase in a test in Tennessee. This result, which may not be typical
demonstrates an economic benefit of $12.90/acre. '
More detailed data on the efficacy and cost effectiveness of captan on
apples and strawberries appears in Part III.
10
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PART II. INITIAL SCIENTIFIC REVIEW
SUBPART A. CHEMISTRY
Page
Synthesis and Production Technology 12
Physical Properties of Captan 15
Analytical Methods 19
Composition and Formulation 26
Chemical Properties, Degradation Reactions and Decomposition
Processes 27
Hydrolysis Reactions - 28
Thermal Decomposition 30
Photolysis Reactions 30
Reactions with Thiols 30
Other Chemical Reactions 32
Occurrence of Captan Residues in Food and Feed Commodities ... 32
Acceptable Daily Intake 34
Tolerances 34
References 38
11
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This section contains a detailed review of available data on captan's
chemistry and presence in foods. Eight subject areas have been examined:
Synthesis and Production Technology; Physical Properties of Captan;
Analytical Methods; Composition and Formulation; Chemical Properties,
Degradation Reactions and Decomposition Processes; Occurrence of Residues
in Food and Feed Commodities; Acceptable Daily Intake; and Tolerances.
The section summarizes rather than interprets data reviewed.
Synthesis and Production Technology
The only major manufacturer of captan in the U0S9 is Calhio Corpora-
tion, a jointly owned subsidiary of Stauffer Chemical Company and Chevron
Chemical Company (part of Standard Oil of California). Their plant is lo-
cated in Perry, Ohio, has annual capacity of 25 million pounds per year,
and is also used for manufacturing folpet, an analog of captan.
Captan is made in a two-step reaction process followed by several
purification steps. The process uses two intermediates which are manu-
factured on site.
One of these intermediates is tetrahydrophthalimide, which is also
made by a two-step reaction:
CH=CH7
I
CH=CH2
Butadiene
100-110°C
0
li
Maleic anhydride
(1)
b'
Tetrahydrophthalic anhydride
0
NH3
200-220°C
0
ii
H20 (2)
The second intermediate is perchloromethyl mercaptan, made by th
following reaction:
CS2 + 3C12
-> CC13SC1 + SC12
(3)
12
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The tetrahydrophthalimide is mixed with sodium hydroxide then
reacted with perchloromethyl mercaptan as follows:
0
NH
+ NaOH
.N-Na + H20
(4)
0
N-Na + CLSCC1,
SCC13 + NaCl (5)
11
0
Captan
The schematic diagram for the production of captan by Calhio is shown
in Figure 1.
Reaction (1) proceeds smoothly with a minimum of by-product. The
anhydride is typically above 99% purity and contains minute quantities
of vinyl cyclohexene and other butadiene polymeric materials as the major
impurities (California Spray-Chemical Corporation, 1955)i'. The reaction
is carried out by bubbling butadiene gas into molten maleic anhydride at
a temperature of 100 to 110°C (Kittleson, 1953)!/.
In Reaction (2), a small amount of colored maleimide resin polymers
are formed from the reaction of ammonia and unreacted maleic anhydride.
The reaction is run at a high temperature to boil off the water, and,
during this process, all of the vinyl cyclohexene and most of the other
volatile impurities are removed. The purity of the imide is typically
98% with residual water and tetrahydrophthalic anhydride being the major
impurities (California Spray-Chemical Corporation, 1955).
Reaction (3) to produce perchloromethyl mercaptan is performed at
0 to 15°C. The pressure is approximately atmospheric or slightly higher.
The reaction is exothermic. Iodine is a common catalyst, but ferric chlo-
ride or aluminum chloride may be used (Sittig, 1967)—'. The final purity
is 96% purity or better (California Spray-Chemical Corporation, 1955).
\_l California Spray-Chemical Corporation, The Chemistry of Captan , Kansas
City, Mo. (31 March 1955).
2_/ Kittleson, A. R., "Preparation and Some Properties of N-Trichloromethyl-
thiotetrahydrophthalimide," J. Agr. Food Chem., 1(10):667-679 (5
August 1953).
3/ Sittig, M., Pesticide Production Processes, Chemical Process Review
No. 5, Park Ridge, New Jersey, Noyes Development Corporation (1967).
13
-------
Vent Vent Vent
A A '
1 1 __. ^_
it 6 f ? f
Scrubber Scrubber Scrubber
t t 1
C$2 e= _ __ __ RMM
Chlorinatoi 1-! Si 11 C~ r. "~" "
C\2 £=
Butadiene c= TMPI
M.A. £-• Reucloi' &•> fluker E> c -- -in-
Storage
•J 1 1
1 I
Scrubber Scrubber .
1 1 Lie
? V
Vent Vent
Source: Lawless, E. W. , and T. L. Ferguson of Midwest Resear
Consultants, The Pollution Potential in Pesticide
roro,
u v
^ Captan _ „ ,
p, 1 Imf °P °
II '1
1 ' J~* 1
9 ?
Baghouse Shipment
1
¥
Venl
ste
uid
ch Institute, and R. von Rumker of RvR
Manufacturing, for the Environmental
Protection Agency, Contract No. 68-01-0142 (January 1972).
Figure 1. Production and waste schematic for captan.
-------
Reaction (4) is a simple mixing-dissolving step.
Reaction (5) (captan production) is controlled at a temperature be-
tween 10 and 30°C, preferably about 20°C, and at essentially atmospheric
pressure. Reaction time is from 10 to 40 min. The reaction is carried
out in an aqueous medium of pH 10.0 to 10.5. No catalyst is used (Sittig,
1967). The pH must be kept as low as possible to prevent decomposition
of the product, but high enough to drive the reaction to completion by
absorbing the HC1 formed.
Kittleson and Nelson (1958)!/ in a U.S. patent describe how the
reaction may be carried out in an inert organic solvent. Possible sol-
vents include ketones, aromatic, aliphatic or chlorinated hydrocarbons.
A tertiary amine is used to absorb the HC1 formed in the reaction.
Kittleson and Yowell (1951)!/ report yields of 85 to 95% in captan
manufacture.
Table 1 presents a list of raw materials and process wastes and
losses.
Physical Properties of Captan
Chemical Name; N-(trichloromethylthio)-4-cyclohexene-l,2-dicar-
boximide.
Common Name; Captan
Trade Names; Merpan, Orthocide, SR-406, Vanicide.
Pesticide Class; Fungicide; Chlorinated organosulfur compound.
Structural formula:
J7 Kittleson, A. R., and J. F. Nelson (to Esso Research), U.S. Patent
2,856,410 (14 October 1958).
2J Kittleson, A. R., and H. L. Yowell (to Standard Oil Development
Company), U.S. Patent 2,553,771 (22 May 1951).
15
-------
Table 1. RAW MATERIALS AND BY-PRODUCTS IN THE MANUFACTURE OF CAPTAN
Raw materials
Material
Received from
Received by
Storage
1. CS2
2. I2
3. C12
4. NH3
5. CaCO-j
6. Maleic
anhydride
7. Butadiene
8. NaOH
Delaware
Michigan
Louisiana
West Virginia,
Kentucky
Missouri,
Pennsylvania,
New Jersey
Texas
Tank cars
Drums
Tank cars
Tank cars
Truck loads
Tank cars
Tank cars
Tank cars
Drums
Used directly from
tanks
Used directly from
tanks
Bulk
Process Wastes and Losses
Material
1. Active ingre-
dient
2. Solvents
3. Liquid
4. Solid paper
5. Metal
6. Miscellaneous
chemicals
Form
Particulates
Amount produced
(Ib/lb AI)
Approximately
4 Lb/day
10 Tons/year
10 Tons/year
25 Tons/year
1,200 Lb/year
Disposition
Asphalt lined set-
tling pond; dis-
charge
Local collector
Local scrap dealers
Buried on plant
property
Source: Lawless et al., op. cit. (1972).
16
-------
Empirical Formula: CgHgCl^NC^S.
Molecular Weight; 300.61.
Analysis; C, 35.967,; H, 2.69%; N, 4.67%; Cl, 35.50%; S, 10.67%;
0, 10.65%.
Physical State Pure Technical
White crystals Yellow to buff colored
amorphous powder
Odor; Odorless Pungent
Melting Point; 178°C (Martin, 1971)!/ 160-170°C (Martin, 1971)
174-176"C (Stauffer, 1965)^7
172-173°C (Merck, 1968)!/ 158-164°G (Stauffer, 1965)
Boiling Point; Decomposes near melting point.
Specific Gravity (20/20°C): 1.73 1.62
Bulk Density; 25-30 lb/ft2
Vapor Pressure; 6 x 10~^ mm Hg at 25°.
pH; 8.0-8.3 Typical (electrometric, 10% dispersion in water).
Particle Size; 9-13 p, Surface average diameter by air permeation.
Captan Content in Technical Product (Stauffer, 1965); 92% Typical.
Seldom less than 90% or more than 94%.
Noncaptan Chlorine (Stauffer, 1965); Analysis by chlorine content
typically gives results almost 2% too high when calculated as
captan.
\J Martin, H., Pesticide Manual, British Crop Protection Council, 2nd
ed. (1971).
2_l Stauffer Chemical Company, "Technical Captan," (Data Sheet) (1965).
3/ Merck Index, The, P. G. Strecher (Ed.), 8th ed., Rahway,
New Jersey: Merck and Company (1968).
17
-------
Solubility of Captan in Various Solvents (Stauffer 1965):
Substance
Tetrachloroethane
Chloroform
Xylene
Dioxolane
Cyclohexanone
Dioxane
Ethyl acetate
Benzonitrile
Acetonitrile
Chlorobenzene
Methyl chloride
Acetone
Ethylene chloride
Nitromethane
Velsicol AR-50
Benzene
Isopropyl alcohol
Toluene
Methyl alcohol
Ethanol
Diethyl ether
Heptane
Stove oil
Carbitol
Water£/
Grams/100 ml of solvent
(25°C)
8.15
8.0
6.5
5.0
4.96
4.7
4.5
4.0 (12°)
3.6 (22°)
3.3
3.0
3.0
2.85
2.0
Less than 2
1.8
0.8
0.7
0.5
0.29
0.25
0.04
Less than 0.5 ppm
Other
temperatures
10 at 77 C, 20 at
88° C
20 at 91"C
9 at 74°C
15 at 50°C
9.1 at 50°C
10 at 61°C
9 at 57°C
20 at 80°C
10 at 84°G
4.5 at 50°C
10 at 78°C
6 at 81°C
10 at 90°C, 20 at
105°C
5 at 60°C
Less than 1% at 70°C
Less than 1% at 60°C
a/ Ortho Technical Information, Chevron Chemical Company (April 1974),
stated that the solubility in water at 25°C is 3.3 ppm.
18
-------
Analytical Methods
This subsection reviews captan's analytical methods and the most
significant of many primary information sources on the methods. The
following information sources are described: (1) Pesticide Analytical
Manual (PAM), vols. I, II, I/ (2) Official Methods of Analysis of the
Association of Official Analytical Chemists.I/ (3) Analytical Methods for
Pesticides and Plant Growth Regulators.j./
The Pesticide Analytical Manual - The "Pesticide Analytical Manual" (PAM)
is published by the Food and Drug Administration, for the purpose of
bringing together procedures and methods used by the FDA laboratories to
examine food samples for the presence of pesticide residues. The PAM is
published in two volumes. Volume I contains procedures for multi-residue
methods (for samples of unknown history which may contain more than one
pesticide). Volume II contains analytical methods used for specific pesti-
cide residues and for specific foods.
Official Methods of Analysis of the Association of Official Analytical
Chemists - The Association of Official Analytical Chemists (AOAC) publishes
an authoritative manual of "Methods of Analysis." A new edition of this
manual is published about every 5 years. The reliability of the methods
must be demonstrated by a published study showing the reproducibility of
the method by professional analysts. Methods and collaborative studies are
published in the Journal of the Association of Official Analytical Chemists.
Analytical Methods for Pesticides and Plant Growth Regulators, Volume VI,
Gas Chromatographic Analysis - This text (Zweig and Sherma, 1972) contains
valuable information concerning gas chromatographic analytical techniques.
It provides a review of literature concerned with formulation and residue
analyses for captan.
Multi-Residue Methods -
Multi-residue methods for captan are described in PAM, Volume I.
Zweig and Sherma (1972) have compiled a detailed review of gas chromato-
graphic residue analyses. AOAC multi-residue methods are not applicable
to captan.
I/ U.S. Department of Health, Education, and Welfare, Food and Drug Administra-
tion, Pesticide Analytical Manual. 2 vols. (1971).
_2/ Association of Official Analytical Chemists, Official Methods of Analysis
of the Association of Official Analytical Chemists, llth ed., Washington,
D.C. (1970).
_3/ Zweig., G, and J. Sherma, Analytical Methods for Pesticides and Plant
Growth Regulators. Vol VI: Gas Chromatographic Analysis, Academic Press,
New York (1972).
19
-------
PAM Procedures - The PAM multi-residue methods apply to the wide variety of
foods tested by the FDA. However, the multi-residue methods are not capable
of detecting and measuring all pesticides. Analytical schemes specified
for the detection of captan are shown in Figures 2 and 3. The various parts
of the schemes shown in Figures 2 and 3 are outlined in detail in the PAM.
(The numbers refer to the chemical numbering system of PAM; the chapter
numbers also refer to PAM.)
From conferences with FDA officials, it was learned that the analytical
system used by the FDA laboratories (in Kansas City) does detect captan.
However, the recoveries are low (about 50%) because analytical response is
not good (detection of captan by the gas chromatographic procedure is somewhat
erratic). However, captan residues are detected only occasionally in the
total diet studies and specific analysis for captan is not routinely made
by the FDA.
A major difficulty appears to be the erratic recovery of captan by the
extraction and cleanup procedure. PAM states that data is unavailable on
the recovery of captan from fatty foods. In the analysis of nonfatty foods,
captan is not recovered in either the 6% or 15% fraction (ethyl ether in
petroleum ether) from the Florisil column. (See PAM Table 20-A). PAM Table
201-G notes that Eluant C (50% methylene chloride, 1.5% acetonitrile and
48.8% hexane) is suitable for captan.
Relative retention times of captan are presented below for various
column packings; the corresponding response for various detectors is also
indicated.
Residue Analysis Principles -
Both the AOAC methods manual and PAM (Vol. II) describe methods for
the specific analysis of captan residues. Zweig and Sherma have provided
a review of specific residue analytical methods for captan.
AOAC Method (Official Final Action) - According to the AOAC method for
specific analysis of captan residues, captan is extracted with benzene.
Water, colored materials, and appreciable amounts of waxes are removed from
the benzene solution using a cleanup mix (a mixture of Nuchar, Hyflo Super-
Cell and anhydrous sodium sulfate). A red color is developed by fusion of
captan with resorcinol (after evaporation) at 135°C. This color changes to
yellow on addition of acetic acid. The concentration of captan is deter-
mined spectrophotometrically at 425 urn using a standard reference curve.
The method is applicable to firm fruits such as apples, pears, peaches
and plums and to green vegetables. '
20
-------
1
Chlorinated (noniomc)
210
Organophosphates
230
See Scheme 762**
Sample Preparation
141
Guidelines for
Compositing
142
Extraction and
Cleanup
Chapter 2
Gas Chromatography
(quantitative)
Chapter 3
Thin Layer
Chromatography
(semi - quantitative)
Chapter 4
Determinative
Methods - other
Chapter 5
Confirmatory Tests
Chapter 6
Chlorinated (ionic)
220
See Scheme 163
* The numbers refer to the decimal numbering system of PAM.
Chapter numbers also refer to PAM.
** Scheme 162 is presented in Figure 2.
Source: PAM (1971).
Figure 2. General scheme for multiple residues*
21
-------
Chlorinated (Noiiionic) 210*
Orgaiiophosphates 230
Proximate Percentage Water
and Fat in Foods and Feeds 202
Fatty Foods
211231
Non Fatty Foods
212 232
Extraction of Fat
211.13
1
Acetonitrile
Partitioning
211.14
1
Extraction and
Partitioning
212.13
Florisil Column
211.15
15% Eluate
J
I
i
U.
2nd Florisil
Column
211.16 a
I
Ac id- Ce lite
Column-
211.16 b
& 2nd Florisil
Column
I
I
I
I
I
L. :
Gas Chromatography
Electron Capture and Thermionic
Dual Detection System 321
i Cos Chromatography
._-*•< Electron Capture Detector
-X
2nd Florisil
Column
211.16a
MgO-Celite
Column
211.16 c
Alkaline
Hydrolys is
211.16 d
& MgO-Celite
Column
Thin Layer Chromatography
Chlorinated 410
Organophosphates 430
The
* The numbers refer to the decimal numbering system of PAM iue
primary analytical scheme is in bold type. Additional'cleanup
and/or quantisation schemes are in italics
Source: PAM (1971).
Figure 3. Analytical Scheme for Chlorinated
(nonionpc) and Organophosphate Residues
22
-------
Column
packing
107o DC 200 on
Gas-Chrom Q
(or Anakrom Q)
15% QF-1,
107, DC 200 on
Gas-Chrom Q
Column
packing
107o DC 200 on
Gas-Chrom Q
15% QF-1,
10% DC 200 on
Gas-Chrom Q
Column
packing
10% DC 200 on
Gas-Chrom Q
15% QF-1,
10% DC 200 on
Gas-Chrom Q
Electron Capture Detector
Retention time
relative to aldrin
(ratio)
1.22
2.10
Halogen Detector
Retention time
relative to sulphenone
(ratio)
1.16
2.03
Sulfur Detector
Retention time
relative to sulphenone
(ratio)
0.95
0.80
Response
(ng for 1/2 FSDl{
at 1 x IP"9
40-50
Response
(ug for 1/2 FSDi/
64 ohms)
3.5
Response
(ug for 1/2
64 ohms)
a/ FSD = Full scale deflection.
t>/ AFS = Amps, full scale.
23
-------
PAM Methods - PAM (1971) lists three methods for specific residue analysis.
The first two methods have been "tested in varying degrees and are considered
reliable without further validation for the product applications indicated."
The third method has not been "thoroughly tested through inter-laboratory
studies."
The First Method - This method is a procedure for the determination of
captan, folpet and difolatan in crops. The crop sample is extracted with
acetonitrile and partitioned into Eluant C. Further cleanup is effected on
a Florisil column utilizing two different solvent systems. The pesticide
residue is measured by gas chromatography using an electron capture detection
system.
Chlorinated insecticides are eluted in the first eluate (20% methylene
chloride in petroleum) and captan, folpet and difolatan in the second (50%
methylene chloride in petroleum ether). Additional confirmation of the
residues can be made using a different column and thin-layer chromatography.
Captan recoveries of 84 to 118% have been obtained on cabbage, carrots
and soybeans fortified at 2 ppm level. The procedure can be applied to a
variety of raw agricultural commodities. The sensitivity is 0.1 ppm.
(Additional information concerning this method is presented in the section
on "Other Methods.")
The Second Method - This method refers to the AOAC procedure, described
earlier. The sensitivity is 10 ppm. This method, however, does not
distinguish between captan and folpet; it may now be obsolete in view of
GLC (gas liquid chromatography) methods.
The Third Method - This method (Archer and Corbin, 1969)i/employs a
thin-layer chromatographic technique to detect captan residues in the
presence of difolatan residues. The method can selectively detect 1 ug of
captan. The sample residue, after extraction from the crop material, is
spotted on a Silica Gel H plate. Detection is with either resorcinol,
glacial acetic acid or tetraethylammonium hydroxide-pyridine spray reagents.
Other Methods - Zweig and Sherma have reviewed several other residue analysis
methods for captan. Kilgore et at. (1967)1' reported a rapid procedure for
determining captan residues on apricots, peaches, tomatoes, and cottonseed.
The residues are extracted with benzene or acetonitrile and analyzed by
_!/ Archer, T. E. and J. B. Corbin, "Detection of Captan Residues in Prune
Fruits and Blossoms by Thin-Layer Chromatography," Bull, of Environ
Contain, and Toxicol. , 4(l):53-63 (1969). " ~
2J Kilgore, W. W. , W. Winterlin, and R. White, "Gas Chromatographic
Determination of Captan Residues," J. Agr. Food Chem 15(6)•303S-
1037 (1967). '
24
-------
electron capture gas chromatography. Residues as low as 0.01 ppm were detected,
and an overall average recovery of captan residues obtained from fortified
control samples was 92%.
Revenue and Ogata (1968)!/ reported the use of a gas chromatography
method for the separation of phaltan (retention = 4.2 min) and captan (5.2
min). Recoveries of the fungicides from fresh papayas fortified at the 1.0
ppm level ranged from 85 to 95%. The procedure involved cleanup of a benzene
extract by a 5 min contact with Nuchar-190 carbon.
Pomerantz et al. (1970)—' determined captan, phaltan, and difolatan in
crops using gas chromatography with electron capture detection. The
procedure involved acetonitrile extraction, partitioning into methylene
chloride-petroleum ether, and cleanup on Florisil. Recoveries were 80 to
110% for six food crops fortified at levels from 2.0 to 0.1 ppm. The method
of Pomerantz et al., is essentially the method used by PAM. None of the GLC
methods have been subjected to a full collaborative study.
Formulation Analysis Principles -
A formulation analysis procedure for captan is described in the
Journal of the AOAC (Anon., 1971)3/. Zweig and Sherma (1972) have provided
a review of two other methods. The Technical Service Division of EPA uses
the AOAC method and the "Hydrolyzable Chlorine" method.
AOAC Method (Official First Action) - According to a change in AOAC method
(Anon., 1971) captan is extracted from inerts with a solution containing
dieldrin (as internal standard) in dioxane. The mixture is analyzed using
any gas chromatography system which will completely separate captan from
dieldrin (under specified conditions, which include a thermal conductivity
or hydrogen flame detector). The ratio of captan peak height to dieldrin
peak height is measured and compared to the ratio from standard captan pre-
pared similarly. It is not completely satisfactory for all samples,
probably due to a tendency of captan to decompose on the GLC column. It has
not yet been given official final action.
This method applies to technical and dry formulated products containing
captan as the only active ingredient.
\J Bevenue, A. and J. N. Ogata, "The Examination of Mixtures of Captan and
Phaltan by Gas Chromatography," J. Chromatogr., 36(4):529-531 (Sept. 1968)
2] Pomerantz, I. H., L. J. Miller, and G. Kava, "Extraction, Cleanup, and
Gas-Liquid Chromatographic Method for the Analysis of Captan, Folpet,
and Difolatan in Crops," J. Assoc. Offic. Anal. Chem., 53(1):154-157
(1970).
_3_/ "Captan (N-Trichloromethylthio)-4-cyclohexene-l,2-dicarboximide) -
Official First Action," J. Assoc. Offic. Anal. Chem., 54(2):451
(1971).
25
-------
Gas Chromatographic Method - A method recommended by Zweig and Sherma employs
a sample of captan (or phaltan) dissolved in acetone. The sample is injected
into a gas chromatograph (thermal conductivity detector) and the quantity of
captan in the sample is determined by comparing the area of the sample peak
with that from a sample of known composition.
Hydrolyzable Chlorine Method - Zweig and Sherma also review an older method
based upon the selective hydrolysis of captan followed by halide determina-
tion. The method is described by Ospenson, et at. (1964)!' in Vol. Ill of
Zweig's text, Analytical Methods for Pesticides, Plant Growth Regulators and
Food Additives. The method is suitable for the assay of both captan and
phaltan and is based on measuring the hydrolyzable chlorine in captan. The
method is basically designed for 100% captan, although with proper care it
could be adapted for high concentration captan formulations. Materials con-
taining hydrolyzable chlorine interfere. The chloride is measured using the
Volhard method on the sample before and after hydrolysis, and the difference
calculated to equivalent captan.
Other Methods - The use of liquid chromatography for analysis of captan
formulations offers considerable promise. An infrared method has also been
used to determine captan in formulation.±J Bromoform or chloroform is used
as a solvent and absorbance is measured at 7.91 microns.
Composition and Formulation
Technical captan is about 92% pure product, the remainder consisting
of sodium chloride, water and unreacted tetrahydrophthalimide (FAO/WHO,
1970)1'.
Captan is physically and chemically compatible with practically all
common and important agricultural pesticides and formulation materials with
the notable exception of alkalies.
Among the alkaline materials, hydrated lime specifically can cause loss
of fungicidal activity. Ground limestone, on the other hand, is quite safe
and can be used in dry mixtures.
_!/ Ospenson, J. N., D. E. Pack, G. K. Kohn, H. P. Burchfield and E. E.
Storrs, "Captan," p. 7, Chapter 2 in Analytical Methods for Pesti-
cides, Plant Growth Regulators and Food Additives. Vol. Ill, Fungicides,
Nematocides and Soil Fumigants, Rodenticides and Food and Feed AdcHMvP.s
Academic Press, New York, New York (1964).~''
21 Collaborative International Pesticide Analytical Council, CIPAC Handbook,
Vol. I, W. Heffer and Sons, Ltd., Cambridge, pp. 172-183 (1970)
3/ FAO/WHO, Food and Agricultural Organization of the United Nations/World
Health Organization, "1969 Evaluations of Some Pesticide Residues in
Food," The Monographs. Geneva (1970). *esiaues m
26
-------
Among the diluents and carriers, all the common types have been used
with captan in a variety of applications with good results. For mixtures
with insecticides and other fungicides, diluents such as talc, prophyl-
lite and sericite are favored for best results. In sensitive applications
where phytoxicity may be a problem, kaolinite diluents may show some
activity with captan and should be tested before adoption.
Captan can be used with moderate amounts of oil or other liquids in
most applications. However, excessive oil or solvent liquids capable of
carrying the fungicide into plant tissues can cause injury in certain
applications (Stauffer, 1965).
Formulations of captan available from the manufacturer include:
Orthocide SOW (wettable powder containing 50% captan by weight) and
Orthocide SOW (wettable powder containing 80% captan by weight). A wide
selection of dusts are available, and several formulations of seed protec-
tants are available.
Chemical Properties, Reactions and Decomposition Processes
Captan is chemically classified as a chlorinated organosulfur com-
pound. The technical product is about 92% pure captan. Several chemical
names have been used in the past. It was originally called N-trichloro-
methylthiotetrahydrophthalimide. Chemical Abstract Services (CAS) for a
while used the name N-trichloromethylthio-4-cyclohexene-l,2-dicarboxirnide.
This is one of the names approved for use on labels by EPA (Caswell et
al., 1972)1/. CAS now uses the name 3a,4,7,7a-tetrahydro-2-[(trichloro-
methyl)thio]-lH-isoindole-l,3(2H)-dione. The structure of captan and
several of its analogs, which are also used as fungicides, is presented
in the following diagram:
0
NSCC13
0
Captan
I/ Caswell, R. L., D. E. Johnson, and C. Fleck, "Acceptable Common
Names and Chemical Names for the Ingredient Statement on Pesti-
cide Labels," (2nd ed.), Environmental Protection Agency,
Washington, D.C. (June 1972).
27
-------
Kittleson (1953), who obtained the original patent for captan, pre-
pared 17 other compounds containing the N-trichloromethylthio group and
found them all to be highly active fungicides. He concluded that the N-
trichloromethylthio group was the active portion of the molecule, but,
according to Metcalf (1971), I/ this conclusion may be an over-simplifica-
tion, because the interaction of the molecule with the fungus appears to
be a highly complex process (see "Reactions with Thiols," p. 29).
Hydrolysis Reactions - The rate of hydrolysis of captan increases with
increasing temperature and increasing alkalinity. The reaction is given
by Melnikov (1971)l/as follows:
0
II
NSCC13 + 2H20 - > NH + C02 + 3HC1 + S (6)
y
H'
0
Gaptan Tetrahydrophthalimide
This reaction is consistent with the observations of Miller (1957),—'
who suggested the formation of HC1 because of the drop in pH from 7.0 to
4.2 when a captan suspension in water was held for 2 weeks at 25°C. He
also used AgN03 to prove that free chloride ions were formed. Daines et
aL (1957) ,_/ however, observed that H2S is also formed. These investiga-
tors used chloride ions and H2S as criteria of captan decomposition.
The rate of hydrolysis with temperature was studied extensively by
Daines et al. (1957). They found that decomposition of a 2% slurry in
water occurred rather slowly at temperatures below 110° F, but at 110°F
hydrolysis was very rapid. California Spray-Chemical Corporation (1955)
held a 2% slurry at 100° C and observed that the hydrolysis was essentially
_!/ Metcalf, R. L., "Chemistry and Biology of Pesticides," Pesticides in
the Environment, R. White-Stevens (ed.), New York, Marcel Dekker
Inc. (1971). '
II Melnikov, N. N., Chemistry of Pesticides. 36 of Residue Rev.. Springer-
Verlag, New York, p. 247 (1971).
3/ Daines, Robert H., R. J. Lukens, E. Brennan, and 1. A. Leone, "Phyto-
toxicity of Captan as Influenced by Formulation, Environment, and
Plant Factors," Phytopathology, 47(9):567-572 (September 1957).
28
-------
complete in 2-1/2 hr. They gave the chemical reaction as:
0
II
,NSCC13 + 3-3/4 H20
Captan
0
II
\
H + 3HC1 + 1/2 H2S
1/4 H2S03 + H2C03
0
Tetrahydrophthalimide
This publication also noted that tetrahydrophthalimide will hydrolyze
further according to Equation (8):
i?
H
H20
0
0
II
C-NH2
C-OH
I!
0
H20
0
II
C-OH
C-OH
II
0
NH
The effect of pH on hydrolysis is very pronounced. Daines et al.
(1957) found that there was little captan decomposition at pH 7.0, very
rapid decomposition at pH 10.6, and nearly instantaneous decomposition
at pH 14. von R'umker and Horay (1972)1.' gave the following values for
hydrolytic stability at various temperature and pH's!
4
7
10
Buffer
Acetate
Citrate
Carbonate
Half-life
20° C
32.4 hr
8.3 hr
< 2 min
40° C
5.3 hr
2.1 hr
< 2 min
_!/ von R'umker, R., and F. Horay, Pesticide Manual, Vol. I., Depart-
ment of State, Agency for International Development (1972).
29
-------
Thermal Decomposition - von R'umker and Horay (1972) state that dry cap-
tan is stable to heat but aqueous suspensions are quickly decomposed at
100°C or in alkaline media. The following thermal stabilities for dry
captan are given:
Half-life at 80°C 213 weeks
Half-life at 120°C 14-1/4 days
At temperatures above the melting point (170°C) dry captan is
rapidly decomposed.
Pyrolysis of captan by dry distillation at 200°C results in the
formation of thiophosgene, tetrahydrophthalimide and "other related prod-
ucts" (California Spray-Chemical Corporation, 1955).
Photolysis Reactions - Lloyd Mitchell (1961)1' of the FDA subjected many
pesticides to ultraviolet radiation of wavelength 253.7 run. The pesti-
cides were spotted on chrpmatographic paper and exposed to the radiation
for a total of 1 hr. Captan was classified in the category of "degrada-
tion complete or practically so." Products were not identified.
However, California Spray-Chemical Corporation (1955) reports that
captan is stable to ultraviolet light. Thin layers of recrystallized
captan were exposed for 24 hr to a 100 W H-6 mercury lamp. The samples
were held at 35"C and purity was checked by melting point and confirmed
by biological assay.
Reactions with Thiols - Thiol compounds react with captan and destroy its
fungitoxicity (Lukens and Sisler, I958)&. Reactions between captan and
thiol groups are believed to be the chemical basis for the fungicidal
activity of captan.
17 Mitchell, Lloyd C., "The Effect of Ultraviolet Light (2537 A) on 141
rh8tiC^meS5!l8nSli^
Chem., 44(4):643+ (1961).
21 Lukens, R. J., and H. D. Sisler, "2-ThiaZOlidinethione-4-Carboxylic
Acid from the Reaction of Captan with Cysteine " Science 127M29Q^
650 (21 March 1958). ' ^^v).
30
-------
According to Lukens and Sisler (1958), the amino acid cysteine re
acts with captan in vitro as follows:
> [H02CCH(NH2)CH2S-]
Cystine
NSCC13 + 2 HSCH2CH(NH2)C02H
Cysteine
Tetrahydrophthalimide
c
II
s
2-Thiazolidinethione-4-
carboxylic acid
CS2 + HC1 + H2S
Captan itself appears capable of reacting only with thiol groups. How-
ever, initial reaction products containing the trichlorothio portion of
the captan molecule and the thiophosgene released by interaction of
captan with thiol groups are apparently capable of reacting with amino,
hydroxyl, thiol, and possibly other groups. Chemical reactions of this
kind within the cell are considered to be responsible for the fungi-
toxicity of captan.
Because captan reacts in a similar manner with sodium dimethyldi-
thiocarbamate (Lukens, 1959)i', it cannot be mixed with dithiocarbamate
fungicides.
_!/ Lukens, R. J., "Chemical and Biological Studies on a Reaction Between
Captan and the Dialkyldithiocarbamates," Phytopathology, 49(6):339-
343 (June 1959).
31
-------
Owens and Blaak (1960)i/ have further investigated the complex in-
teractions of captan with thiols. Captan was shown to produce the cor-
responding disulfide when reacted with thiophenol or 4-nitrothiophenol.
The work of Owens and Blaak (1960) confirmed the belief that thiophosgene
is an intermediate in the reactions of captan with thiols.
Other Chemical Reactions - The basis for one analytical method for cap-
tan residues is fusion with resorcinol [m-CgH^OH^] followed by a colori-
metric determination. The structure of the product is still not known,
but it is known to have the empirical formula C-^HgO^S (Pomerantz, et al.
1969) I/.
Occurrence of Captan Residues in Food and Feed Commodities
The Food and Drug Administration (FDA), Department of Health, Educa-
tion and Welfare, monitors pesticide residues in the nation's food supply
through two programs. One program, commonly known as the "total diet
program," involves the examination of food ready to be eaten. This in-
vestigation measures the amount of pesticide chemicals found in a high-
consumption varied diet. The samples are collected in retail markets and
prepared for consumption before analysis. The other program involves the
examination of large numbers of samples, obtained when lots are shipped
in interstate commerce, to determine compliance with tolerances. These
analyses are complimented by observation and investigations in the grow-
ing areas to determine the actual practices being followed in the use of
pesticide chemicals.
A majority of the samples collected in these programs are catego-
rized as "objective" samples. Objective samples are those collected where
there is no suspicion of excessive residues or misuse of the pesticide
chemicals. All samples of imported foods and fish are categorized as
"objective" samples even though there may be reason to believe excessive
residues may be found on successive lots of these food categories.
JY Owens, G., and G. Blaak, "Chemistry of the Reactions of Dichlone and
Captan with Thiols," Contrib. Boyce Thompson Inst., 20(8):475-497
(December 1960).
_2/ Pomerantz, I., L. Miller, E. Lustig, D. Mastbrook, E. Hansen, R.
Barren, N. Dates and J. Y. Chen, "The Fusion of Captan N-(Trichloro-
methylthio-4-Cyclohexene-l,2-Dicarboximide with Resorcinol,"
Tetrahedron Letters, (60) :5307-5310 (December 1969).
32
-------
Market-basket samples for the total diet studies are purchased from
retail stores, bimonthly, in five regions of the United States. A shopping
guide totaling 117 foods for all regions is used, but not all foods are
represented in all regions because of differences in regional dietary
patterns. The food items are separated into 12. classes of similar foods
(e.g., dairy products; meat, fish and poultry; legume vegetables; and
garden fruits) for more reliable analysis and to minimize the dilution
factor. Each class in each sample is a "composite." The food items and
the proportion of each used in the study were developed in cooperation
with the Household Economics Research Division, USDA, and represents the
high consumption level of a 16- to 19-year-old male. Each sample represents
a 2-week supply of food.
Surveillance samples are generally collected at major harvesting and
distribution centers throughout the United States and examined in 16 FDA
district laboratories. Some samples may be collected in the fields immedi-
ately prior to harvest. Surveillance samples are not obtained in retail
markets. Samples of imported food are collected when offered for entry into
the United States.
DeBaun et al.—' investigated the nature of the residue on apple fruit
and foliage under field conditions, using captan-l^C=0, but only partially
characterized the residue. In surface washes of the fruit, the major com-
ponent of the residue is captan (68-79%), lesser amounts of component THPI
(5.2-7.6%), THPAM (tetrahydrophthalamic acid) (0.4-1.3%), and little or no
captan-epoxide or THPI-epoxide (< 1%). Captan-epoxide was not previously
reported as a component of the residue. Upon analyzing the apple peel and
pulp, it was found that captan predominated in the peel, while THPI predomi-
nated in the pulp, the remainder being THPAM, captan-epoxide and THPI-
epoxide. The epoxides did not exceed 0.5 ppm in apple peel and 0.3 in
apple pulp under the conditions of this investigation.
The data submitted to EPA by Chevron Chemical Company and Stauffer
Chemical Company on feeding studies involving cattle and swine indicates
only the carry-over of captan residues, THPI and THPAM2~V. These studies were
done before the metabolism was investigated by DeBaun, Hoffman and coworkers.
Stauffer and Chevron Chemical Companies have conducted studies to investigate
the metabolism more fully. However, in finding unexpected metabolites, they
have reopened questions of whether or not the metabolites are toxic and
whether or not they should be looked for as components of the residue. Toler-
ances regarding meat, milk, poultry and eggs are on an interim basis.
JY Debaun, J. R., L. A. Gruwell, and J. J. Menn, "The Fate of Captan (carbony
-l^c) on Field-Grown Apple Trees," Stauffer Chem. Co. report, May 1974.
2/ Harris Laboratories, "Captan Study," unpublished report to American Seed
Trade Association, Lincoln, Nebr. (1972).
I/ Harris Laboratories, "Results from the Analysis of Hog Tissues for Tetra-
hydrophthalimide," unpublished report, Lincoln, Nebr. (February 1973).
4/ Industrial Bio-Test Laboratories, "Tissue Residue Study for Captan and
Tetrahydrophthalimide in Crossbred Steers Fed Technical Captan," unpub-
lished report to American Seed Trade Association, Northbrook,
111. (December 1972).
33
-------
Evaluation of the published data concerning pesticide residues in food
has revealed that captan has not been reported as a significant residue in
any food class. From conferences with FDA officials, it was learned that
the analytical system used by the FDA laboratories (in Kansas City) does
detect captan. However, the recoveries are low (about 50%) because analyt-
ical response is not good (detection of captan by the gas chromatographic
procedure is somewhat erratic). However, captan residues are detected only
occassionally in the total diet studies and analytical studies specifically
for captan are not ordinarily performed.
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 ADI for captan is 0.125 mg/kg. This level was set at the 1965
Joint Meeting of the FAO Committee on Pesticides in Agriculture and the
WHO Expert Committee on Pesticide Residues. A major review was held again
at the 1969 Joint Meeting (FAO/WHO, 1970), but any pesticide may be reviewed
at any annual meeting if new evidence is available. The ADI for captan is
considered a temporary value, but as of the 1971 Joint Meeting it has not
been changed (FAO/WHO, 1972)^./. All available research on captain's bio-
chemical effects, toxicology, and teratology was used to determine the ADI.
Tolerances
U.S. Tolerances - Section 408 of the Food, Drug and Cosmetic Act, as amended,
gives procedures for establishing tolerances for pesticide chemicals on raw
agricultural commodities. Section 409 applies to food additives, including
pesticide chemicals on processed foods. Tolerances for captan on raw
agricultural commodities are published in the Code of Federal
Regulations, Title 40. They are summarized in Table 2. Tolerances
for processed foods are cited in Title 21 of the Code as: "50 ppm
on captan residues in or on washed raisins when present as a result
of fungicidal treatment by preharvest application to grapes and
postharvest application during the drying process."3/
_!/ Lu, F.C., "lexicological 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)
21 FAO/WHO, Food and Agricultural Organization of the United Nations/World
Health Organization, "Pesticide Residues in Food," Report of the 1971
Joint FAO/WHO Meeting on Pesticide Residues, World Health Oreaniza-
tion Tech. Kept. Series No. 502, Geneva (1972^"
I/ Code of Federal Regulations, Title 21, Chapter l', Subchapter B Parf
121, Subpart A, Section 123.40. P ' C
34
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Table 2. U.S. TOLERANCES FOR CAPTAN ON RAW AGRICULTURAL COMMODITIES
Ul
ppm Crop ppm
2 Almonds 2
100 Almond hulls 2
25 Apples 2
50 Apricots 25
25 Avocados 25
25 Beans (dry or succulent) 25
100 Beet greens 25
2 Beet roots 50
25 Blackberries 25
25 Blueberries (Huckle- 2
berries) 2
2 Broccoli 100
2 Brussels sprouts 50
2 Cabbage 2
25 Cantaloupe 50
2 Carrots 25
2 Cauliflower 50
50 Celery 50
100 Cherries 25
25 Citrus (grapefruit, 2
lemons, limes, oranges, 25
tangerines) 25
Crop ppm
Collards 25
Corn (sweet) 50
Cottonseed 25
Cranberries 25
Cucumbers 25
Dewberries 25
Eggplant 25
Grapes 2
Honeydew melon 2
Kale 100
Kohlrabi 25
Lettuce 25
Mangoes 50
Mustard 25
Nectarines 2
Onions, dry bulb
Onions, green
Peaches
Pears
Peas
Peppers
Pimento
Pineapple
Plum (prunes)
Potatoes
Pumpkin
Quinces
Raspberries
Rhubarb
Rutabaga
Soybeans (dry and succulent)
Spinach
Strawberries
Squash (summer and winter)
Tangelos
Tomatoes
Turnips
Source: U.S. Environmental Protection Agency, EPA Compendium of Registered Pesticides,
Vol. II; Fungicides and Nematicides, Washington, D.C. (1973).
-------
According to Lu (1973), U.S. tolerances which are established should
not result in the maximum ADI being reached each day. He gives the following
reasons:
1. The tolerance reflects the maximum level of residue
resulting from good agricultural practice, but this
level is often not reached.
2. The tolerance is based on the assumption that the
particular pesticide is used on all food in the class
in question, and this is rarely the case.
3. Much of the residue will be lost in storage, proces-
sing and cooking.
The tolerances are also based upon the entire product as purchased in
the market. However, the product, as purchased, may not be entirely consumed.
International Tolerances - Tolerances established by individual nations may
be based on recommendations of the FAO/WHO Expert Committee on Food Additives.
The Committee evaluates all residue data submitted by interested parties and
uses the following criteria (FAO/WHO, 1962)!./ for making tolerance recom-
mendations:
1. Decide upon the effective level of the food additive under
consideration that would be needed in good technological
practice.
2. Examine the possible uses and list all the foods in which
the food additive might be used.
3. Calculate the daily intake level that might occur if the
food additive was used in all the foods for which it might
be a useful additive, working on the basis of the average
intake of the food materials containing the additive. This
average intake for appropriate population groups is obtained
from national food consumption surveys.
4. Obtain the necessary information from which to calculate the
average body weight of the population group concerned (usually
between 50 to 70 kg).
5. From this information, calculate the intake of the additive
in milligrams per kilograms of body weight per day.
I/ FAO/WHO, Food and Agricultural Organization of the United Nations/
World Health Organization, "Evaluation of the Toxicity of a Number
of Antimicrobials and Antioxidants," Sixth Report, Joint FAO/WHO
Expert Committee on Food Additives, World Health Organization Tech
Kept. Series No. 228, Geneva (1962). '
36
-------
6. Check the figure against the acceptable intakes given for the
substances in the table. If it falls within the unconditional
intake zone, the situation is satisfactory and the level
proposed may be accepted. If it falls within the conditional
intake zone, further scientific advice is required before the
level of use proposed is accepted.
The recommendations for captan tolerances established by the 1969
Joint Meeting of the FAO and WHO (FAO/WHO, 1972), are as follows:
Commodity Tolerance (ppm)
Apples, cherries 40
Pear 30
Apricots 20
Citrus fruit, peaches, plums, rhubarb, tomatoes 15
Strawberries, raspberries, cranberries,
cucumbers, lettuce, green beans, pepper 10
Raisins 5
37
-------
References
Archer, T. E. and J. B. Corbin, "Detection of Captan Residues in Prune
Fruits and Blossoms by Thin-Layer Chromatography," Bull, of Environ.
Contain, and Toxicol., 4(l):55-63 (1969).
Association of Official Analytical Chemists, Official Methods of Analysis
of the Association of Official Analytical Chemists, llth ed., Washington,
D.C. (1970).
Benvenue, A., and J. N. Ogata, "The Examination of Mixtures of Captan and
Phaltan by Gas Chromatography," J. Chromatogr., 36(4):529-531 (September
1968).
California Spray - Chemical Corporation, The Chemistry of Captan, Kansas
City, Mo. (March 1955).
"Captan (N-(Trichloromethylthio)-4-cyclohexene-l,2-dicarboximide) Official
First Action," J. Assoc. Offie. Anal. Chem., 54(2):451 (1971).
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).
Code of Federal Regulations, Title 21, Chapter 1, Subchapter B, Part 121,
Subpart A, Section 123.40.
Collaborative International Pesticide Analytical Council, CIPAC Handbook,
Vol. I, W. Heffer and Sons, Ltd., Cambridge (1970).
Daines, Robert H., R. J. Lukens, E. Brennan, and I. A. Leone, "Phytotoxicity
of Captan as Influenced by Formulation, Environment, and Plant Factors,"
Phytopathology, 47 (9):567-572 (September 1957).
De Baun, J. R. , L. A. Gruwell and J. J. Menn, "The Gate of Captan (carbonyl-
14C) on Field-Grown Apple Trees," unpublished report, Stauffer Chemical
Company, Westport, Connecticut (1974).
FAO/WHO, Food and Agricultural Organization of the United Nations/World
Health Organization, "Evaluation of the Toxicity of a Number of Anti-
microbials and Antioxidants," Sixth Report, Joint FAO/WHO Expert Com-
mittee on Food Additives, World_Health Organization Tech. Rept Series
No. 228, Geneva (1967). " K—'
FAO/WHO, Food and Agricultural Organization of the United Nations/World
Health Organization, "1969 Evaluations of Some Pesticide Residues in Food,'
The Monographs, Geneva (1970). '
FAO/WHO, Food and Agricultural Organization of the United Nations/World
Health Organization, "Pesticide Residues in Food," Report of the 1971
Joint FAO/WHO Meeting on Pesticide Residues, World Health Organization
Tech. Rept. Series No. 502, Geneva (1972). " —
38
-------
Harris Laboratories, "Captan Study," unpublished report to American Seed
Trade Association, Lincoln, Nebr. (1972).
Harris Laboratories, "Results from the Analysis of Hog Tissues for
Tetrahydrophthalimide," unpublished report, Lincoln, Nebr. (February 1973).
Industrial Bio-Test Laboratories, "Tissue Residue Study for Captan and
Tetrahydrophthalimide in Crossbred Steers Fed Technical Captan," unpub-
lished report to American Seed Trade Association, Northbrook, 111.
(December 1972).
Kilgore, W. W., W. Winterlin, and R. White, "Gas Chromatographic Deter-
mination of Captan Residues," J. Agr. Food Chem., 15(6):1035-1037 (1967).
Kittleson, A. R., and H. L. Yowell, (to Standard Oil Development Company),
U.S. Patent 2,553,771 (22 May 1951).
Kittleson, A. R., "Preparation and Some Properties of N-Trichloromethyl-
thiotetrahydrophthalimide," J. Agr. Food Chem., 1(10):667-679 (5 August
1953).
Kittleson, A. R., and J. F. Nelson (to Esso Research), U.S. Patent
2,856,410 (14 October 1958).
Lawless, E. W., and T. L. Ferguson of Midwest Research Institute, and
R. von Rumker of RvR Consultants, The Pollution Potential in Pesticide
Manufacturing, for the Environmental Protection Agency, Contract No.
68-01-0142 (January 1972).
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.
Lukens, R. J., "Chemical and Biological Studies on a Reaction Between
Captan and the Dialkyldithiocarbamates," Phytopathology, 49(6):339-343
(June 1959).
Lukens, R. J., and H. D. Sisler, "2-Thiazolidinethione-4-Carboxylic Acid
from the Reaction of Captan with Cysteine," Science, 127(3299)) :650 (21
March 1958).
Martin, H.,. Pesticide Manual, British Crop Protection Council, 2nd ed. (1971)
Melnikov, N. N., Chemistry of Pesticides, 36 of Residue Rev., Springer-
Verlag, New York, p. 247 (1971).
Merck Index, The, P. G. Stretcher (ed.), 8th ed., Rahway, New Jersey:
Merck and Company (1968).
Metcalf, R. L., "Chemistry and Biology of Pesticides," Pesticides in the
Environment, R. White-Stevens (ed.), New York, Marcel Dekker, Inc. (1971).
39
-------
Mitchell, Lloyd C., "The Effect of Ultraviolet Light (2537 A) on 141 Pesti-
cide Chemicals by Paper Chromatography," J. Assoc. Off. Agr. Chem.,
44(4):643+ (1961).
Ortho Technical Information, Chevron Chemical Company (April 1974).
Ospenson, J. N., D. E. Pack, G. K. Kohn, H. P. Burchfield and E. E.
Storrs, "Captan," p. 7, Chapter 2, in Analytical Methods for Pesticides,
Plant Growth Regulators and Food Additives, Vol. Ill, Fungicides,
Nematocides and Soil Fumigants, Rodenticides and Food and Feed Additives,
Academic Press, New York, New York (1964).
Owens, G., and G. Blaak, "Chemistry of the Reactions of Dichlone and
Captan with Thiols," Contrib. Boyce Thompson Inst., 20(8):475-497
(December 1960).
Pomerantz, I. H., L. J. Miller, and G. Kava, "Extraction, Cleanup, and
Gas-Liquid Chromatographic Method for the Analysis of Captan, Folpet,
and Difolatan in Crops," J. Assoc. Offie. Anal. Chem., 53(1):154-157
(1970).
Pomerantz, I., L. Miller, E. Lustig, D. Mastbrook, E. Hansen, R. Barron,
N. Gates and J. Y. Chen, "The Fusion of Captan N-(Trichloromethylthio-
4-Cyclohexene-l,2-Dicarboximide with Resorcinol," Tetrahedron Letters,
(60):5307-5310 (December 1969).
Sittig, M., Pesticide ProductionProcesses, Chemical Process Review No.
5, Park Ridge, New Jersey, Noyes Development Corporation (1967).
Stauffer Chemical Company, "Technical Captan," (Data Sheet) (1965).
U.S. Department of Health, Education and Welfare, Food and Drug Adminis-
tration, Pesticide Analytical Manual, 2 vols. (1971).
U.S. Environmental Protection Agency, EPA Compendium of Registered Pesti-
cides, Vol. II: Fungicides and Nematocides (1973).
von Rumker, R., and F. Horay, Pesticide Manual, Vol. I., Department of
State, Agency for International Development (1972).
Zweig, G., and J. Sherma, Analytical Methods for Pesticides and Plant
Growth Regulators, Vol. VI; Gas Chromatographic Analysis. Academic
Press, New York (1972).
40
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PART II. INITIAL SCIENTIFIC REVIEW
SUBPART B. PHARMACOLOGY AND TOXICOLOGY
CONTENTS
Acute, Subacute and Chronic Toxicity 43
Toxicity to Laboratory Animals 43
Acute Oral Toxicity - Rats 43
Subacute and Chronic Oral Toxicity - Rats 45
Acute Toxicity - Mice 46
Subacute and Chronic Oral Toxicity - Mice 46
Acute Oral Toxicity - Dogs 46
Subacute Oral Toxicity - Dogs 46
Acute Oral Toxicity - Hamsters 48
Chronic Oral Toxicity - Hamsters 48
Acute Oral Toxicity - Rabbits 48
Subacute Toxicity - Rabbits 48
Chronic Oral Toxicity - Rabbits 48
Acute Oral Toxicity - Monkeys 48
Subacute Toxicity - Monkeys 49
Chronic Oral Toxicity - Monkeys 49
Potentiation - Rats 49
Toxicity to Domestic Animals 49
Acute Oral Toxicity - Chickens 49
Subacute and Chronic Oral Toxicity - Chickens 49
Acute Oral Toxicity - Swine 51
Subacute and Chronic Oral Toxicity - Swine 51
Acute Oral Toxicity - Sheep 52
Subacute and Chronic Oral Toxicity - Sheep 53
Acute Oral Toxicity - Cattle 53
Subacute Toxicity - Cattle 53
Dermal Effects 53
Symptomatology and Pathology Associated with Mammals 53
Symptomatology 53
Pathology 53
Summary 55
41
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CONTENTS (Continued)
Page
Metabolism of Captan 55
Absorption 55
Distribution 56
Excretion 56
Biotransformation 56
Summary 59
Effects on Reproduction 59
Laboratory Animals 59
Domestic Avian Species 60
Teratogenic Effects 61
Monkeys 61
Rabbits 62
Dogs 65
Hamsters 66
Rats 68
Mice 68
Avian Embryotoxicity 70
Behavioral Effects 70
Toxicity Studies with Tissue Cultures 70
Mutagenic Effects 70
Oncogenic Effects yg
Effects on Man gQ
Summary g^
Reproduction g-^
Teratology '. '. 81
Mutagenesis ' 82
Oncogenesis g^
References
-------
This section is concerned with information on the acute, subacute and
chronic toxicities of captan in laboratory and domestic animals (rats, mice,
dogs, hamsters, rabbits, monkeys, chicken, swine, sheep, and cattle). A
brief review is given of the characteristic symptoms and pathology of captan
poisoning in mammals. The metabolism of captan is also discussed in relation
to absorption, distribution, excretion, and biotransformation. Other subjects
that have been reviewed are: the effects on reproduction, malformation of
th6 young, and mutagenic effects. Limited investigations were found relating
to the effects of captan on tissue culture. Data was also found on oncogenic
effects and effects on man. The section summarizes rather than interprets
data reviewed.
Acute, Subacute and Chronic Toxicity
Toxicity to Laboratory Animals -
Acute oral toxicity - rats - The acute oral toxicity of captan for rats
ranges from 8,400 to 12,600 mg/kg body weight (see Table 3). The average
LDso from the data in the table is 10,000 mg/kg (FCH, 1970;i/ Ben-Dyke et al. ,
1970; "LI Krijnen and Boyd, 19701/).
There are no reported studies on differences in toxicity to captan among
male and female rats. It appears reasonable to assume that males are as
susceptible to oral dosing as females.
Krijnen and Boyd (1.971)—' performed a series of tests in which they
showed that the LD5Q of captan was influenced considerably by the nutritional
state of the test animal (rat). They found that reduction of dietary protein
to one-third of the optimal intake lowered the growth rate but did not have
much effect on the oral LD5Q. When rats were fed at protein levels which
were one-seventh optimal intake (3.5% casein), they did not grow and were
much more susceptible to captan intoxication. When rats were fed a diet con-
taining no casein, they lost weight and were more susceptible to all pesticides
tested; sensitivity to captan was increased 2,100 times. The LD50 was reduced
from 12,600 mg/kg at optimal protein levels to 479 mg/kg at 3.5 casein.
I/ Farm Chemicals Handbook, Meister Publishing Company, Willoughby, Ohio
(1970).
21 Ben-Dyke, R. , D. M. Sanderson, and D. N. Noakes, "Acute Toxicity Data
for Pesticides (1970)." World Rev. Pest. Cont., 9:119-127 (1970).
_3/ Krijnen, C. G., and E. M. Boyd, "Susceptibility to Captan Pesticide of
Albino Rats Fed from Weaning on Diets Containing Various Levels of
Protein," Food Cosmet. Toxicol.. 8:35-42 (1970)
47 Krijnen, C. G., and E. M. Boyd, "The Influence of Diets Containing from
0 to 81 Percent of Protein on Tolerated Doses of Pesticides," Comp. Gen.
Pharmacol.. 2:373-376 (1971).
43
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Table 3. THE TOXICITY OF CAPTAN - RATS
Sex and age
of animals
Mixed sex,
adults
Mixed sex,
adults
Male,
adults
Male,
adults
Female,
pregnant
Mixed sex,
adults
Male,
young
Duration
of test
28 days
28 days
3 days
100 days
Toxicity calculation
LDcn, oral
LDc;Q, oral
LD^Q, oral
LD^Q, oral
Toxicity, dietary
"No-effect level"
LD5Q, 100-day
Toxicity measured
9,000 mg/kg
8,400 mg/kg
12,600 mg/kg
479 mg/kg
2,000 mg/kg
1,000 ppm
diet = 50
mg/kg/day
916 mg/kg/day
Comments
on effect
References
a/
y
c,d/
Diet was grossly c,d,e/
deficient in protein
Lowered weight gain _f/
of maternal animal
only effect noted
h/
a/ FCH, op. cit. (1970).
W Ben-Dyke et al., op. cit. (1970).
£/ Boyd, E. M., and C. G. Krijnen, "Toxicity of Captan and Protein-Deficient
Diet," J. Clin. Pharmacol., 8:225-234 (1968).
d/ Krijnen and Boyd, op. cit. (1970).
e/ Krijnen and Boyd, op. cit. (1971).
£_/ Kennedy, G. , 0. E. Fancher, and J. C. Calandra, "An Investigation of the
Teratogenic Potential of Captan, Folpet, and Difolatan," Toxicol. Appl.
Pharmacol., 13:420-430 (1968).
£/ Anon., FAO/WHO, "Captan," 1969 Evaluations of Some Pesticide Residues in
Food, 33-44 (Geneva) (1970).
h/ Boyd, E. M., and E. Carsky, "The 100-Day LD5Q Index of Captan," Acta
Pharmacol. Toxicol., 29:226-240 (1971).
-------
In a study on teratogenic effects of captan, Kennedy et al. (1968) fed
pregnant female rats for 3 days at 2,000 mg/kg and did not notice any toxic
effects on the maternal animals except a lowered weight gain.
Subacute and chronic oral toxicity - rats - In a study of relatively
long duration, Boyd and Carsky (1971) administered captan to young male
rats by gavage in a range of doses once daily for 100 days (Table 3).
The oral LD5Q (100 days) was found to be 916 1 233 mg/kg/day. In the
survivors, the toxic syndrome subsided at 22 to 42 days and at this time
the only symptoms which persisted were mild hypothermia and aciduria.
From days 43 through 100 the captan-treated rats ate more food than the
controls. At 100 days, however, the treated survivors weighed 30% less
than the controls. At no time were there any significant changes in
urinary blood, glucose or protein.
The 100 day LD5Q index has been proposed as a single figure measure-
ment of chronic lethal toxicity. The index is the LDso (100 days) ex-
pressed as a percentage of the acute LD5Q (one dose). Using the acute
oral LDso (one dose) of captan for rats (12.5 ± 3.5 g/kg) as reported by
Boyd and Krijnen (1968) and the oral LDso (100 days) found to be 0.916 ±
0.233 g/kg/day by Boyd and Carsky (1971), the oral 100 day LDso index of
captan was calculated to be 7.3 - 1.9 (equivalent to 9,000 ppm) (Boyd and
Carsky, 1971).
As reported by Boyd and Carsky (1971), inhibition of spermatogenesis
was also particularly marked in rats which survived for 100 days (0.916 g/
kg/day).
According to FAO/WHO (1970),—' the upper level of captan which is
toxicologically safe in rats is 1,000 ppm in the diet, equivalent to 50 mg/
kg body weight per day.
In a study using mixed-sex adult rats, captan was fed for 13 weeks at
several concentrations at a maximum level of 10,000 ppm. All experimental
groups were started at a level of 500-ppm captan and the dosage was increased
in gradual increments until a 5,000-ppm level was reached in 4 weeks and the
10,000-ppm level was reached after 7 weeks. The only effect noted was weight
suppression with both males and females .±/
A two-year study was conducted using both male and female rats. The
test animals were fed diets that contained up to 5,000 ppm of technical
captan. The female rats in the group which received 1,000 ppm of captan
had a reduction in weight gain for the last 16 weeks of the test but were
equal to controls for the first 88 weeks. Female rats receiving 5,000 ppm
technical captan also displayed reduced weight gain.
_!/ FAO/WHO, "Captan," 1969 Evaluations of Some Pesticide Residues in Food,
33-34 (Geneva)(1970).
_2/ Gray, E., Report of Hazelton Laboratories on Captan, EPA Pesticide
Petition No. 15, 1954.
45
-------
A second group of rats, both male and female, were given 10,000 ppm of
technical captan for 24 weeks and then divided into two parts. One-half of
the animals were then fed recrystallized captan for 30 weeks and one-half
were continued on the technical material for 30 weeks. Both sexes on diets
containing 10,000 ppm of either technical or recrystallized captan exhibited
growth depression although signs of systemic toxicity were not observed.
At autopsy indications of testicular atrophy were found in three animals.!/
Acute toxicity - mice - The intraperitoneal LD5Q was reported in a
study by Arnold (FAO/WHO, 1970) to be 10 mg/kg body weight for the mouse
(Table 4). Studies on acute oral toxicity, dermal toxicity, or inhalation
toxicity were not found.
Subacute and chronic oral toxicity - mice - No subacute oral toxicity
studies were found for mice. Only one reference to chronic studies with
mice was found and this was the study of Innes et al. (1969), ±J which
was conducted primarily as a study on the carcinogenic potential of captan
(Table 4). In this test, male and female mice were given captan at a dose
of 215 mg/kg body weight per day by gavage from 7 days of age to 4 weeks
of age. From 4 weeks to 18 months, captan was added to the diet at 560 ppm.
There was no indication that the fungicide caused an increased mortality.
Acute oral toxicity - dogs - Acute oral toxicity of captan for dogs
was not reported in the literature examined in this study.
Subacute oral toxicity - dogs - No subacute oral toxicity studies were
found for dogs. However, a well defined chronic study on captan toxicity
was reported (Fogleman, 1955)—'. Groups of four dogs were used, each con-
sisting of two males and two females. The animals were started on a dose
regime of 0 (Group I) , 10 (Group II), 25 (Group III) and 50 (Group IV) mg/kg
body weight of captan. At the beginning of week 10, the dose levels were
increased from 25 to 50 mg/kg (Group III) and from 50 to 100 mg/kg (Group
IV). At week 18, the doses were again increased to 100 mg/kg (Group III)
and 300 mg/kg (Group IV). The captan was given to the dogs in gelatin
capsules 6 days a week for 66 weeks.
All the dogs in Group I were normal at the completion of the test.
Group II animals which had received 298 daily doses of captan (10 mg/kg/day)
were normal and alert. They exhibited either maintenance or weight gains.
The Group III dogs had received 54 daily doses of 25 mg/kg, 48 doses of 50
mg/kg, and then 100 mg/kg daily doses for the remainder of the test. These
animals appeared normally alert and did not exhibit any signs of toxicity.
I/ Weir, E., Report of Hazelton Laboratories on Captan EPA Pesticide
Petition No. 15, (1956).
2/ Innes, J. R. M., B. M. Ulland, M. G. Valeric, L. Petrucelli L
Fishbein, E. R. Hart, A. J. Pallotta, R. R. Bates, H L Falk
J. J. Gart, M. Klein, I. Mitchell, and J. Peters, "Bioassay of
Pesticides and Industrial Chemicals for Tumorigenicity in Mice-
A Preliminary Note," J. Natl. Cancer Inst., 42(6):1101-1114 (1969)
3/ Fogleman, R. , Report of Hazelton Laboratories on Captan EPA Pestir-irL
Petition No. 15 (1955). •""-<-iae
46
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Table 4. TOXICITY DATA ON CAPTAN - LABORATORY ANIMALS
Condition
Test and sex of Duration Toxicity
Toxicity
animal animal of test calculation measured
Mice Mixed sex, -- LD50' i'p'
adults
Mice Mixed sex, 18 months Toxicity,
adults dietary
10 mg/kg
560 ppm
Comments on effect
__
Lethal toxic effects
not noted
Dogs Mixed sex, -- "No-effect 100 mg/kg/day
adults level"
Hamsters Female, 15 days Toxicity,
pregnant dietary
Hamsters Female, 5 days Toxicity,
pregnant oral
Rabbits Female, 6 days Toxicity,
pregnant oral'
Rabbits Female, 13 days Toxicity,
pregnant oral
Rabbits Mixed sex, 14 days Toxicity,
adults oral
Monkeys Female, 11 days Toxicity,
pregnant oral
Monkeys Female, 14 days Toxicity,
pregnant oral
Monkeys Mixed sex, — "No-effect
adults level"
1,000 mg/kg
500 mg/kg/day
80 mg/kg/day
75 mg/kg/day
500 mg/kg/day
25 mg/kg/day
75 mg/kg/day
12.5 mg/kg/day
Given from days 1-15
of gestation
Lower gestational
weight gain
20% mortality of
mothers
Given during days
7-12 of gestation
Given on days 6-18
of gestation
Resulted in pathology
being induced
Given on days 22-32
of gestation
Given on days 21-34
of gestation
--
References
*/
b/
£/
*'
I/
£/
d/
&/
y
u
£/
a/ Arnold (1967). Quoted in Anon., FAO/WHD report (1970).
b_/ Innes et al. , op. cit. (1969).
£/ Anon., FAO/WIIO report, op. cit. (1970).
d/ Kennedy et al., op. cit. (1968).
e/ Robens, op. cit. (1970).
^/ Fabro, S., R. L. Smith, and R. T. Williams,
"Embryotoxic Activity of Some
Pesticides and Drugs Related to Phthalimide," Food Cosmet. Toxicol., 3:
587-590 (1965).
£/ Szuperski, T. , and A. Grabarska, "Changes in
after Experimental Oral Administration of
Szk. Roln. Olsztynie., 28:279-284 (1972).
Internal Organs of
Captan Fungicide,
Rabbits
Zesz . Nauk.
h/ Courtney (1968). Quoted in Anon., FAO/W11D report (1970).
i/ Vondruska (1969). Quoted in Anon., FAO/WHO
report (1971).
-------
The animals in Group IV were also normally alert and, with the exception
of one dog which had a weight loss, did not exhibit signs of toxicity.
Liver and kidney weights were slightly increased in the dogs which
received the 300-mg/kg dose. There was no evidence of systemic toxicity.
Gross changes or histopathological changes in tissues due to treatment at
any dose level were not observed. There were no significant changes in
hematological or biochemical findings.
Acute oral toxicity - hamsters - An oral LDso was not found in the
literature for hamsters. Oral subacute toxicity was reported in a study
by Robens (1970)i/ for pregnant females. The animals were fed captan for
5 days at 500 mg/kg body weight per day. The reported mortality follow-
ing this dosage was 20%. Kennedy et al. (1968), in a study on the tera-
togenic effect of captan fed to pregnant female hamsters for 15 days at
1,000 mg/kg body weight, reported that lethal toxic effects were not
observed although the females did exhibit a lowered gestational weight
gain.
Chronic oral toxicity - hamsters - Data on the long-term effects of
captan have not been reported for hamsters.
Acute oral toxicity - rabbits - Data on oral toxicity of captan to
rabbits has not been determined by direct tests. Indirect toxicity data
(mortality resulting during teratogenic tests, etc.) are all that are
available in the open literature.
Subacute toxicity - rabbits - Fabro et al. (1965) gave pregnant
New Zealand white rabbits daily oral doses of 80 mg/kg body weight of
captan for 6 days (7 through 12 of gestation). These authors did not
report any lethality. Lethal toxic effects were also not observed in
a study by Kennedy et al. (1968) in which pregnant rabbits were treated
for 10 days at a captan level of 75 mg/kg/day.
Oral subacute toxicity of captan administered at 500 mg/kg/day for
14 days (equivalent to 16,500 ppm) was studied by Szuperski and Grabarska
(1973) in rabbits. These investigators reported that a dosage of 500 mg/kg/
day level resulted in serious dystrophic changes in the kidneys, lungs,
spleen, stomach, and intestinal mucosa. Captan at 500 mg/kg/day also
inhibited the storage of polysaccharides, including glycogen, in the liver
and muscles.
Chronic oral toxicity - rabbits - Reports on this subject with
rabbits as the test animal were not found.
Acute oral toxicity - monkeys - Acute toxicity (LD.n) for captan in
monkeys has not been reported. The only toxicity data that exist come
from indirect tests where mortality or systemic toxic symptoms are
reported in animals used primarily for teratogenic studies.
I/ Robens, J. F. , "Teratogenic Activity of Several Phthalimide Derivatives
in the Golden Hamster," Toxicol. Appl. Pharmacol. . 16:24-34 (1970) .
48
-------
Subacute toxicity - monkeys - According to Courtney, (FAO/WHO, 1970),
lethal toxic effects were not observed in a test involving pregnant female
monkeys fed captan at a level of 25 mg/kg/day for 11 days. Vondruska
(FAO/WHO) reported the same findings for pregnant females fed 14 days at
75 mg/kg/day. FAO/WHO (1970) also reported that there were no adverse
effects of 11-day captan dosages to monkeys at levels of 12.5 mg/kg/day.
Chronic oral toxicity - monkeys - Information on captan's chronic
effects in monkeys has not been reported.
Potentiation - rats - The potentiation of toxicity of captan by DDT
was considered in one study (Hazelton Laboratories, 1957) .i' Rats were
treated by stomach tube with DDT, with captan, and with a combination of
the two that contained 1 part DDT to 36 parts captan. Eight groups of four
rats each were used in the test.
Potentiation was not observed. The acute toxicity (LD5Q) of captan
alone was determined to be 9,000 mg/kg.
Toxicity to Domestic Animals -
Acute oral toxicity - chickens - Acute LD5Q values have not been
reported for captan with chickens as the test animal.
Subacute and chronic oral toxicity - chickens - A feeding trial was
conducted by Link et al. (1956).2_/ in which chickens were fed under ordinary
feeding conditions using corn that had been previously treated with captan.
The test was started on 2-day-old chicks which were fed on a high energy
ration containing corn that had been treated with 0.93 oz of captan per 100
Ib (in the mixed ration, captan equaled 0.032%). The chicks were kept in
electric brooders until 4 weeks of age at which time they were transferred
to well-ventilated houses and fed from open feeders.
When mortality of the treated chicks was compared with that of the
controls after 74 days of feeding, it was seen that captan in the ration
had not resulted in increased mortality (see table 5).
Ackerson and Mussehl (FAO/WHO, 1970) were reported to have fed chicks
a diet containing 320 ppm captan for 28 days without any observable detri-
mental effects.
The results of one study were reported in which groups of 15 hens
were fed diets containing captan (technical) at 0, 100, 1,000, and 10,000
ppm for 90 days. The birds which received 100 and 1,000 ppm of the fungi-
cide were reported normal in respect to food consumption, egg production,
and survival. In those birds which were given diets containing 10,000 ppm
I/ Hazelton Laboratories, Report on Captan, 1957, EPA Petition No. 124,
amended.
2J Link, R. P., J. C. Smith, and C. C. Morrill, "Toxicity Studies on
Captan-Treated Corn in Pigs and Chickens," J. Am. Vet. Med. Assoc.,
128:614-616 (1956).
49
-------
Table 5. SUMMARY OF ORAL TOXICITY DATA FOR CAPTAN - DOMESTIC ANIMALS
Ul
o
Test
animal
Chickens
Chickens
Swine
Swine
Swine
Swine
Cattle
Sex and age
of animal
Mixed sex,
chicks
Mixed sex,
chicks
Mixed sex,
adult
Mixed sex,
young
Mixed sex,
weanlings
Mixed sex,
adult
Heifer
a/ Acker son and Muss eh 1
b/ Link et al., op. cit.
Duration
of test
28 days
74 days
96 days
90 days
119 days
25 weeks
6 days
(1953). Quoted
(1956).
Toxicity measured
320 ppm
320 ppm
480 ppm
540 ppm
1,680 ppm
4,000 ppm
250 mg/kg/day
in Anon. , FAO/WHO
Comments on effect
Lethal toxic effects not seen
Lethal toxic effects not seen
Remained normal
No abnormalities noted
No gross pathological effects
observed
Toxicity not noted
Lethal toxicity noted after
3 days
report (1970).
References
a/
b/
b/
c/
d/
e/
f/
£/ Batte (1953). Quoted in Anon., FAO/WHO report (1970).
d/ Meade and Warner (1954). Quoted in Anon., FAO/WHO report (1970).
e/ Johnson, D. F., "A Toxicity Test of n-Trichloromethylthiotetrahydrophthalimide,"
Southwestern Vet., 8:55-57 (1954).
_f/ Palmer, J. S. , and R. D. Radeleff, "The Toxicologic Effects of Certain Fungicides
and Herbicides on Sheep and Cattle," Ann. N. Y. Acad. Sci., 111:729-736 (1964).
-------
captan, food refusal, weight loss and decreased egg production were observed.
Autopsy did not reveal any gross pathological effects. By analysis it was
also demonstrated that eggs and tissues of the hens did not store captan.
Fertility and hatchability were not affected at any captan concentration
tested.i/
In a study of the teratogenic potential of captan, chickens were fed
a diet containing 2,300 ppm technical captan (reported to be equal to 75
mg/kg body weight) for 6 weeks. Adverse effects were not observed on body
weight gain, food consumption, behavior or egg production. Hatchability
was not affected ..?_'
Acute oral toxicity - swine - Reports dealing with the acute toxicity
of captan to pigs were not found in the open literature of the sources
used for this study.
Subacute and chronic oral toxicity - swine - Eight half-grown pigs
(shoats) were fed captan-treated corn in a study conducted by Batte (FAO/
WHO, 1970). Captan was incorporated in the diet to provide a level of 540
ppm. The feeding studies were carried out for three months. It was
reported that the dietary administration of captan did not affect the rate
of food consumption, the rate of growth or the general health of the animals
when comparisons were made with control animals that had not received
captan in their diet. It was also reported that there were no gross
abnormalities observed in any of the animals on the captan diet.
According to Meade and Warner, weanling pigs have been fed diets
containing captan at 420, 820, and 1,680 ppm for 119 days (FAO/WHO, 1970).
It was reported that this study did not demonstrate any gross pathological
lesions that could be attributed to the presence of captan in the diet.
It has also been reported that pigs fed 500 and 4,000 ppm captan
in the diet did not develop any abnormal symptoms when fed the fungicide-
treated ration for 22 to 25 weeks.
Link et al. (1956) conducted two feeding tests with pigs. In the
first test seven gilts were used for trials and in the second, two gilts
and two barrows were used. The test animals were fed a ration that con-
sisted of corn treated with captan at 0.93 oz/100 Ib. This ration was
fed from self-feeders for 96 days.
The concentration of captan on the corn was calculated to be 0.058
and 0.048% in the finished feed.
_!/ Weir, R., Report of Hazelton Laboratories on Captan, 1957, EPA Pesticide
Petition No. 15.
2J Palazzolo, R., Report of Industrial Bio-Test Laboratories on Captan,
1966, EPA Pesticide Petition No. 15.
51
-------
The presence of captan did not appear to affect the palatability of
the ration so feed refusal was not a factor. Feed efficiency was slightly
better in the treated animals than it was in the controls. Deaths were
not observed in the treated group and histopathological examination of
liver and kidney tissues failed to reveal any significant variations
from normal. Chemical analysis of various tissues including fatty tissue
also failed to reveal the presence of residues.
Differential leukocyte counts and total erythrocyte counts of
captan- treated pigs differed little from similar counts on control
animals indicating that the feeding of captan did not affect the blood-
forming tissues.
Acute oral toxicity - sheep - Acute toxic ity data (LD^g) were not
available in the non-proprietary literature used for this study. However,
Palmer (1963)i' conducted one test to determine acute toxicity of captan to
sheep after a single oral dose.
Wethers at least 1 year old were used in these tests and were
treated with captan administered with a dosing syringe. Four sheep
were used; one for each of two dose levels and two for one dose. Obser-
vations were carried out for 5 weeks after dosing.
The results of these acute tests are as follows:
Dose (mg/kg) Observed effect Results of observed effect
200 None None
250 Poisoned Died
250 Poisoned Recovered
500 Poisoned Died
The sheep treated at the highest level (500 mg/kg) showed evidence
of cardiac deficiency with excessive fluid in the thoracic and abdominal
cavities. The liver exhibited petechial hemorrhages, the gall bladder
was distended and the gastrointestinal tract was acutely inflamed.
Data presented by Palmer and Radeleff (1964) show that sheep are
regularly poisoned by single doses of 250 mg/kg or higher but that at
levels of 50 to 100 mg/kg the animals can eliminate most of the material
without showing any signs of toxicity.
_!/ Palmer, J. S., "Tolerance of Sheep to Captan," J. Am. Vet. Med Assoc
143:513-514 (1963). ::
52
-------
Subacute and chronic oral toxicity - sheep - Sheep given captan at
levels of 100 and 200 mg/kg body weight 5 days a week for 23 weeks
developed depression and anorexia with weight loss. After captan admin-
istration was discontinued the animals recovered without complications.
Sheep which were given captan 5 days per week for 23 weeks at 5 to
50 mg/kg body weight did not evidence any ill effects when compared with
the untreated controls (Palmer, 1963).
Acute oral toxicity - cattle - Toxicity data for captan to cattle
are very limited and acute LD50 values do not exist.
Subacute toxicity - cattle - One study was reported in which one
animal was given multiple doses of captan at 250 mg/kg for six doses.
It was reported that the animal died and that symptoms of poisoning were
present after the first three doses (Palmer and Radeleff, 1964). Symp-
toms of poisoning were reported as diarrhea and abortion.
Dermal Effects
Studies of captan's irritation potential on rabbits demonstrated that
the compound had very low irritation and little or no sensitizing properties
for the rabbit. In studies with guinea pigs, when ten daily intracutaneous
injections of 0.1 ml of 0.1% captan in normal saline served as the sensitiz-
ing dose, the challenge or elicitation tests demonstrated captan to be a
moderate sensitizer. In human patch tests, a captan paste (50% captan in
water) when applied directly to the skin caused no irritation after 24 hr of
continuous application (R.T. Vanderbilt Co., Inc., 1969)—.
Symptomatology and Pathology Associated with Mammals
Symptomatology - The signs of intoxication most often reported for
sheep have been depression and anorexia with weight loss, the degree depend-
ing upon the dosage. After captan is discontinued symptoms disappear with-
out complication.
The clinical signs of intoxication of rats with captan, as reported by
Boyd and Kirjnen (1968), include: irritability, epistaxis, listlessness,
soft stools, soiling of fur, hypothermia, anorexia, oligodipsia, loss of
body weight, oliguria, alkalinuria, glycosuria, and hematuria.
Irritability, epistaxis, listlessness and soft stools reached a peak
of intensity on the second and third days.
The listlessness observed was considered to be due in part to a fall
in body temperature which reached a maximum at 24 hr (dose dependent). On
the third and fourth days, diuresis and aciduria occurred. The immediate
cause of death was cardiac or respiratory failure.
JY R. T. Vanderbilt Co., Inc. Vancide© 89: Summary Report of Toxicity
Tests, Technical Data Sheet (April 23, 1969).
53
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Table 6. HISTOPATHOLOCICAL OBSERVATIONS ON RATS ADMINISTERED CAPTAN
Organ
Adren.il glands
Brain
At death with In ^8 hqurj<
Normal appearance
Heraorrhaglc caplllary-venoua
congest ton of brain and meningea
At death during first 24 daya In survivors at IQO daya
Lipold droplets prominent in
cortex
Uipold droplets prominent
Areai of capillary-venous con- Mild hypernemta
gestion of cerebrum, cerebellum
and men Inges
Gastrointestinal tract:
cardiac stomach
pyloric stomach
Kidneys
Lungs
Muscle (ventral
abdominal wall)
Marked capl llary-venous congestion
of the lamina propria and sub-
tnucosa; hemorrhagic, leukocyte-
infiltrated ulcers
Marked vascular congestion at the
mouths of the gastric glandu
Capillary-venous congestion of the
vllll
Marked cap!llary-venous congestion
and hemorrhage of the lamina
propria and submucosa
Vascular congestion of the lamina
propria and submucosa
Occasional capillary congestion and
hemorrhage
Marked capillary-venous congestion,
especially in the loop region
Sinusoidal congestion; cloudy swell-
ing of the hepatic cells
Normal appearance; some hypememia
or congestion
Cross Btrlation weak
Congestion of the lamina propria Hypertrophy of the strati-
with infiltrative ulcers tied equamous epithelium
Congestion with hemorrhagic
necrotic ulcers
Congestion of the villi and
aubmucoea
Capillary-venous congestion of
the lamina propria and sub-
mucoea
Mild congestion
Normal appearance
Cap!llary-venous congestion in
the region of the loop of
Henle, occasional tubular
cloudy swelling and Infection
Diffuse cloudy swelling
Oedema, congestion, venous
thrombosis and occasionally
pneuraonltis
Normal appearance
Normal appearance
Hypertrophy and hypernemia
Hypertrophy and hyperncTTiia
Normal appearance
Normal appearance
Mild cloudy swelling of the
tubules
Normal appearance
Areas of capillary-venous
congestion
Normal appearance
Salivary (submaxillary)
glande
Skin
Spleen
Testes
Thymus gland
Cap!llary-venous congestion
Normal appearance
Normal appearance
Normal appearance
Vascular congestion of Interstitial
tissue
Capillary-venous congestion and mild
loss of thymocytes
Deficiency of serous zymogenlc Minor deficiency of zy-
granules mogenic granules
Normal appearance
Red pulp atrophied Imbeculae
prominent
Marked Inhibition of spermato-
genesis, interstitial con-
gestion
Marked loss of thymocytes,
atrophy
Normal appearance
Normal appearance
Deficiency of normal sperm
Marked loss of thynocytesl
atrophy
Data from Boyd and Krijnen (1968) and Boyd and Carsky (1971).
54
-------
Recovery of survivors was accompanied by diuresis and a rapid gain in
body weight. After 4 weeks, the weight, water content and appearance of
body organs were practically normal.
Pathology - Gross pathology has been described in detail only for the
rat, but the clinical signs should be similar for most mammals.
The gross pathology observed at autopsy on rats which died of captan
intoxication was reported by Boyd and Krijnen (1968). The lesions and
percent incidence observed were splenic atrophy (87%), congested brain
and meninges (67%), atrophy of thymus gland (60%), dark liver (60%),
gastric ulcers (33%), hemorrhagic small bowel (16%), congested stomach
(13%), erect, edematous penis (10%), congested cecum and colon (6%), and
congested lung (6%).
It can be seen that splenic atrophy is observed regularly and that
the majority of dead animals also exhibit congested brain and meninges,
atrophied thymus gland and a dark liver (Boyd and Krijnen, 1968).
A summary of histopathological observations, when death occurs early
(48 hr), late (21 days), and in survivors is presented in Table 6. This
table is a combination of the results presented by Boyd and Krijnen (1968)
and Boyd and Carsky (1971).
Summary - The level of captan causing no significant toxicological effects
in monkeys and dogs was 12.5 mg/kg/day and 100 mg/kg/day, respectively.
The LD50 in rats ranges from approximately 8,400 to 12,600 mg/kg of
body weight.
Swine have consumed 4,000 ppm of captan over a 175-day period with-
out the appearance of any toxic symptoms.
Based on one investigation, cattle seem to be more sensitive to cap-
tan than some other species, six doses of 250 mg/kg/day produced lethality.
Also, another ruminant species, sheep, is poisoned by single doses of 250
mg/kg or higher.
The symptoms of captan poisoning in rats are irritability, epistaxis,
listlessness, hypothermia, anorexia, oligodipsia, loss of body weight,
oliguria, alkalinuria, glycosuria and hematuria.
The 11)50 in rats ranges from approximately 8,400 to 12,600 mg/kg of
body weight.
Metabolism of Captan
Absorption - Engst and Raab (1973)—' reported that captan is rapidly
absorbed from the rat gastrointestinal tract.
Engst, R., and M. Raab, "Zum Metabolismus fungizider Phthalimid-
Derivate in lebens - mittelchemischtoxikologischer Sicht," Nahrung,
17:731-738 (1973).
55
-------
Distribution - Captan is rapidly decomposed in both human and rabbit
blood in vitro experiments. When 500 mg/kg captan was injected into
rabbits, no captan could be detected in the blood during a 56-hour
sampling period. The metabolite tetrahydrophthalalimide (THPI) reached
a peak concentration of 25 >ig/ml at 25 hours (Crossley, 1967) .i/
Feeding studies with captan demonstrated that it was not stored in eggs
or flesh of poultry or the tissues of pigs (Anon., FAO/WHO report, 1970)
Excretion - Engst and Raab (1973) reported that a given dose of captan
was virtually completely excreted in the feces of rats within 3 days.
It has been suggested (Anon., FAO/WHO report, 1970) that tetrahydro-
phthalamic acid is a principal metabolite of captan excreted in the
urine.
The metabolic fate of captan in albino rats was reported by DeBaun
et al. (1974) .I./ These investigators conducted their studies using a
trichloromethyl-^c-captan and determined the distribution of orally
administered captan 4 days after treatment. They found that 51.8% was
present in urine, 22.8% in expired air, 15.9% in feces and 0.6% in
tissues.
The l^C activity associated with the tissues after oral treatment
with [l^C] captan was reported to probably be due to incorporation of
1^C02 into tissue macromolecules via intermediary metabolic routes.
Metabolism of captan may involve the evolution of thiophosgene
which is detoxified in part by at least three mechanisms: (1) oxida-
tion and/or hydrolysis to C02; (2) reaction with a cysteine moiety to
yield thiozolidine-2-thione-4-carboxylic acid; and (3) reaction with
sulphite to produce dithiobis (methanesulphonic acid). The gastro-
intestinal tract probably plays a major role in degradation of captan
and its metabolism.
Large accumulations of captan in general and in specific organs in
particular were not observed. There were no significant differences
between tissue residue values obtained from male or female animals.
Biotransformation - Shtenberg (1972)_3/ reported that the toxicity of
captan was 26 times greater in animals kept on a protein deficient diet.
Nelson (1971).z/ found that captan induces mitochondrial swelling in rat
liver. In the absence of an energy source, initial swelling can be
_!/ Crossley, J., "The Stability of Captan in Blood," Unpublished report,
file no. 721.11, Chevron Chemical Co., Richmond, Calif. (October 2, 1967)
2J DeBaun, J. R., J. B. Miaullis, J. Knarr, A. Mihailovski, and J. J.
Menn, "The Fate of N-Trichloro[14C]methylthio-4-cyclohexene-i 2-
dicarboximide ([14C]captan) in the Rat," Xenobiotica. 4:101-119 (1974)
_3/ Shtenberg, A. E., "Diet Background and the Body Sensitivity to Toxic
Substances," Gig. Sanit, 37:73-76 (1972).
47 Nelson, B. D., "Induction of Mitochondrial Swelling by the Fungicide
Captan," Biochem. Pharmacol., 20(4):749-758 (1971).
56
-------
inhibited by 2,4-dinitrophenol and KCN. These two chemicals do not
inhibit later swelling, indicating a two-phase phenomenon--one energy-
dependent and the other a passive phase. The trichloromethyl moiety
of captan was found to be the active portion that induced mitochondrial
swelling. It was assumed that captan interacts with mitochondrial
membranes, presumably sulfhydryl groups. According to Engst and Raab
(1973), 5% of an LD.-Q dose of captan given to rats produces a 54% reduc-
tion of erythrocyte SH levels within 3 hr. The reduction of SH groups
was still 25%, after 24 hr. Serum and liver SH groups were also dimin-
ished by 187» and 11%, respectively. Serum glutamic-pyruvic transaminase
and lactic dehydrogenase activities were reduced about 20%. No captan
could be detected in the blood by gas chromatographic or thin-layer
chromatographic techniques. Only metabolites tetrahydrophthalimide and
tetrahydrophthalic acid could be detected.
Recent investigations by DeBaun, Hoffman and coworkers have further
clarified the nature of the residue by feeding radio-labeled captan to
the rat. Of special interest here is the work of Hoffman et al. (1973).!/
who identified a number of unexpected, previously unreported metabolites
from the 1,2-dicarboximido-4-cylohexene (tetrahydrophthalimide or THPI)
moiety of captan. These metabolites arose in three of four pathways
after the hydrolytic cleavage of captan-l^C=0 to THPI and trichloro-
methylthio moieties. The major pathway in the rat apparently involves
ring hydroxylation of the THPI to 3-OH-THPI, and further degradation to
3-OH-THPAM. The second pathway involves epoxidation of THPI to THPI-
epoxide, followed by hydrolysis to 4,5-di-OH-THPI. (See Figure 4.) If
the urinary distribution is any indication, then it would appear that
the major component of the residue is 3-OH-THPI (38%) , lesser amounts
of component THPI (15%), other metabolites including THPI-epoxide (5-12%),
and little if any captan per se (0.4%).
Gale et al. (1971)2/ demonstrated that in vitro captan was a potent
inhibitor of incorporation of thymidine, purine, and L-leucine into the
acid insoluble fraction of Ehrlich ascites tumor cells. Prior addition
of sulfhydryl groups or albumin to the media prevented this effect.
Glycolysis was highly sensitive to captan; this could be prevented with
added thiol groups also.
I/ Hoffman, L.J., J. R. Debaun, J. Knarr, and J. J. Menn, "Metabolism
of N-(trichloromethylthio)!, 2-dicarboximido l^C-4-cyclohexene
(Captan) in the Rat," Stauffer Chemical Co., Westport, Conn.
(August 1973).
21 Gale, G.R., A. B. Smith, L. M. Atkins, E. M. Walkers, Jr., and R. H.
Gadsden, "Pharmacology of Captan: Biochemical Effects with
Special Reference to Macromolecular Synthesis," Toxicol. Appl.
Pharmacol., 18:426-441 (1971).
57
-------
II CAPTAN
O
3-OH-THPAM
RAT (R)
GOAT (G)
C-OH
THPAM
THPI-EPOXIDE
|| 4,5-diOH-THPI
O
Figure 4. Metabolic Pathway for
Captan-14c=0 in the Rat and Goat
58
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A report by the World Health Organization (FAO/WHO, 1970) suggests that
in the presence of cysteine or glutathione, captan is matabolized to
tetrahydrophthalimide, thiophosgene and chloride ion, carbon disulfide and
sulfide. If cysteine is present, an additional compound, a substituted
thiazolidinethione, has also been identified. Menzie (1969)!/ points out
that the carbon disulfide was erroneously identified and should really be
carbonyl sulfide, as identified by gas chromatography.
Summary -
1. Captan is rapidly absorbed from the gastrointestinal tract and
rapidly destroyed in the blood.
2. It does not accumulate in the tissues of pigs or chickens.
3. Captan reacts readily with cysteine, glutathione, or other
compounds containing SH groups.
4. Captan induces mitochondrial swelling by two mechanisms, one
of which is energy dependent.
5. The major metabolic products of captan are tetrahydrophthalimide,
chloride ion, thiophosgene, carbonyl sulfide, hydrogen sulfide, and
2-thiazolidinethione-4-carboxylic acid.
Effects on Reproduction
Laboratory Animals - A three-generation reproductive study (FAO/WHO, 1970)
was conducted with rats which received technical captan in their diet in
concentrations of 0, 100, 500,and 1,000 ppm. Groups of 16 female animals
were used and two litters were produced in each generation. No significant
differences were found between control and captan-treated rats with respect
to fertility, gestation, viability or lactation indices or in the weanling
weights in the first two generations. No effects were observed in the
third generation except a slightly lowered lactation index for the group
receiving 1,000 ppm of captan. Histopathological examination of tissues
from 10 pups receiving 1,000 ppm captan in the third generation revealed
no damage.
A study by Zhorzholiani (1971)—' indicated that captan is gonado-
tropic. Rats and mice given daily oral doses of captan at 6 to 57 mg/kg
and 2.5 to 20 mg/kg body weight, respectively, showed decreased sperm
motility and abnormal changes in fetal development.
I/ Menzie, C. M. "Captan," Metabolism of Pesticides, U.S. Bureau of
Sport Fisheries and Wildlife, Special Scientific Report—Wildlife
No. 127, 67-71 (1969).
2J Zhorzholiani, V. S., "Effect of Prolonged Administration of Captan
on the Function of the Gonads," Soobshch. Akad. Nauk. Gruz., SSR,
64(3):749-751 (1971).
59
-------
Studies on the effect of captan on the reproductive fitness of
DBA/2J male mice were performed by Collins (1972b).I/ Polygenic repro-
ductive fitness was tested using two generations of male mice given
oral doses of 50 to 100 mg/kg body weight per day for 5 days. A known
inutagen, trie thylenemelamine (TEM), was used as the positive control.
TEM produced decreases in overall productivity (as measured by the fer-
tility index) and decreased survival from birth to day 4, and from day 5
to weaning at 21 days. Captan-treated animals showed a decrease in
fertility index, although neither dose rate produced as severe decreases
as TEM administered at the rate of 0.1 mg/kg body weight. A decrease in
average weaning weight was also observed in the first litter of the
second generation for the 100 mg/kg dosage of captan.
Domestic Avian Species - Technical grade captan was fed to hens at levels
of 100, 1,000 and 10,000 ppm for a period of 90 days:
Captan
Hens Roosters (ppm)
1 15 3 0
2 15 -- 100
3 15 — 1,000
4 15 3 10,000
Captan did not alter fertility or hatchability at any level. There was
a reduction in food consumption of the birds on the 10,000-ppm diet
which caused a decrease in weight. The number of eggs produced by this
group was reduced by 80% compared to the controls. No gross pathology
was observed (Weir, 1957).
Hens in one study consumed a diet containing 2,300 ppm (equivalent
to 75 mg/kg body weight) captan. The test group (five male and 18 female
leghorn chickens) was maintained on the diet for 6 weeks. One female in
the test group died, none in the controls. The control hens produced
432 eggs; the treated hens produced 428 eggs. Slightly more than 70%
of the control eggs hatched and 77.1% of the test eggs hatched. No
abnormal physical or behavioral reactions were noted in either test
or control groups-?.',
I/ Collins, T. F. X., "Effect of Captan and Triethylenemelamine (TEM)
on Reproductive Fitness of DBA/2J Mice," Toxicol. Appl. Pharmacol
23:277-287 (1972b). ^ S2i '
2_l Palazzolo, R. , Industrial Bio-Test Laboratories Report on Captan,
EPA Pesticide Petition No. 124.
60
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Teratogenic Effects
Teratology is the study of congenital malformations. The
teratogenicity of a compound is the result of damage to certain cells,
or their death in a developing organism at some point where the suscepti-
bility is at a maximum. Avian teratology involves damage to the embryo
that may bring about death or cause malformations (Durham and Williams,
1972)!/.
The structure of captan has a moiety (ortho dicarboximido) similar
to that of the proven teratogen, thalidomide. This similarity has
prompted studies on the teratogenic effects of these compounds to labor-
atory animals. From a metabolic point of view, the breakdown of captan
is not like that of thalidomide; captan has an easily broken N-S bond,
thalidomide has a strong N-C bond.
In 1970, a search was made for metabolites of thalidomide which might
be similar to those found in the degradation products of captan, folpet
and captofol. No chemical compounds were found in common. The formation
of an aliphatic fragment due to hydroxylation, decarboxylation, and/or
other reactions from phthalic and tetahydrophthalic moieties is conceivable,
but whether this aliphatic fragment would be associated with teratogensis
is doubtful because of its instability and lack of known toxicity.
Investigations of biological effects, enzyme inhibition, and tera-
togenesis have revealed that it is the intact molecule (thalidomide)
which causes malformations. However, since the intact thalidomide
molecule has been shown to have teratogenic activity, and since the
breakdown of captan differs from thalidomide, the concern for the
possible teratogenic effect of captan as it related to thalidomide is
not supported.
Monkeys - In a study by Courtney (FAO/WHO, 1968) groups of seven pregnant
rhesus monkeys were given daily oral doses of 6.25, 12.5 or 25 mg/kg body
weight of captan on days 22 through 32 of gestation. Thalidomide was
used as a positive control at dosage levels of 5 mg/kg body weight per
day in six animals and at 10 mg/kg body weight per day in four animals.
Fetuses were recovered on approximately day 84 of gestation by caesarian
section. The fetuses were examined for organ and skeletal defects.
Fetal mortality occurred in three of seven monkeys at the 25 mg/kg level.
The fetal mortality in the parent colony not fed captan was 13.2% on 439
conceptions. There was no abnormality among any fetuses in either of the
three dose levels of captan.
_!/ Durham, W. F. , and C. H. Williams, "Mutagenic, Teratogenic, and
Carcinogenic Properties of Pesticides," Ann. Rev. Entomol., 17:123-
148 (1972).
61
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In another study (Vondruska et al., 1971)!/ captan was administered
orally to a group of pregnant monkeys (Rhesus and stump tail) at levels
of 10 25, and 75 mg/kg body weight. Doses were given on days 21 through
34 of'gestation. Thalidomide was also administered to a positive control
group at levels of 5 and 10 mg/kg body weight. As shown in Table 7,
neither abnormal fetuses nor abortions occurred in the captan-fed group.
No systemic toxic effects were observed in the mothers, even though
exposure was for longer periods of time and at higher levels than with
thalidomide.
Rabbits - During a study by Fabro (1965) four pregnant New Zealand white
rabbits were given daily oral doses of 80 mg/kg body weight during days
7 to 12 of gestation. Five additional rabbits were given oral doses of
150 mg/kg body weight of thalidomide (positive controls) and five rabbits,
used as negative controls, received no treatment. As indicated in Table
8, no embryotoxicity was observed in litters from the captan-fed rabbits.
In a more detailed study by Kennedy et al. (1968) a group of six
pregnant Dutch belted rabbits were given 75 mg/kg body weight per day of
technical captan, orally on days 6 through 16 of gestation. Three other
groups, each containing five to seven New Zealand white rabbits, were
given 18.75, 37.5 or 75 mg/kg body weight per day on days 6 through 18
of gestation. A control group (no treatment) and a positive control
group (75 mg/kg thalidomide) were included. Two additional groups of
Dutch belted rabbits were given oral doses of 75 mg/kg body weight of
the captan metabolites phthalimide and tetrahydrophthalimide (THPI).
As shown in Table 8, no teratogenic effects were observed with captan
or the two metabolites. Young obtained from treated does appeared
grossly normal, possessed well-defined skeletal structures, were of
normal size and showed excellent survival during a 24-hr incubation
period following recovery at gestation day 29. Females given thalidomide
!_/ Vondruska, J. F., 0. E. Faucher, and J. C. Calandra, "An Investigation
into the Teratogenic Potential of Captan, Folpet, and Difolatan in
Nonhuman Primates," Toxicol. Appl. Pharmacol., 18:619-624 (1971).
62
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Table 7. RESULTS OF CAPTAN AND THALIDOMIDE ADMINISTRATION
TO PREGNANT MONKEYS
U>
Test material
Captan
Thalidomide
R = Rhesus monkeys;
Data from Vondruska
Dose
(mg/kg)
10.0
25.0
75.0
5.0
5.0
10.0
10.0
Gestational
days of
dosing
21-24
21-34
21-34
26-28
24-30
25-27
24-30
10.0 23-29
S = stump-tailed macaques.
et al., op. cit. (1971).
Pregnant
females Normal Abnormal
dosed fetuses fetuses Abortions
3R,4S 3R,4S
7R 7R
3R,4S 3R,4S
2S -- 2S
IS -- IS
11R.3S 2R 6R,2S 3R,1S
IS -- -- IS
2S -- — 2S
-------
Table 8. TERATOCENIC ACTIVITY OF TIIALIDCMIDE, CAFTAN
AND CAPTAN METABOLITES IN RABBITS
Species
Rabbit
Rabbit
Rabbit
Rabbit DB+
Rabbit NZ4
Rabbit DB
Rabbit NZ
Rabbit DB
Rabbit NZ
Rabbit NZ
Rabbit NZ
Rabbit DB
Rabbit DB
Oral
dose
Compound (mg/kg)
None
Thalldomide 150*
Captan 80
None
None
Thalldomide 75.0*
Thalldomide 75.0
Captan 75.0
Captan 18.75
Captan 37.5
Captan 75.0
Phthallmide** 75.0
THPI** 75.0
Number
of
pregnant
females
5
5
4
7
10
7
10
6
6
7
5
10
9
Dosed,
gestational
days
--
7-12
7-12
6-16
6-18
6-16
6-18
6-16
6-18
6-18
6-18
6-16
6-16
Total
number of
implantations
41
46
37
52
66
55
74
43
46
56
39
66
66
Average
number of
implantations
8.
9.
9.
7.
6.
7.
7.
7.
7.
8.
7.
6.
7.
2
2
2
4
6
9
4
2
7
0
8
6
3
Number of
resorptions
3
19
3
0
2
15
10
1
11
2
33
3
9
Average
litter
size
7
5
8
7
6
5
6
7
5
7
1
6
6
.6
.4
.5
.4
.4
.7
.4
.0
.8
.7
.2
.3
.3
Number
of
normal
fetuses
38
18
34
51
64
26
40
42
35
54
6
63
57
Number
of
terata Reference
0
9 a/
0
1
0
14 b/
24
0
0
0
0
0
0
* Daily oral dose.
~t~ Dutch belted (thalldomlde susceptible).
^ New Zealand white (thalidoraide susceptible),
** Captan metabolite.
a./ Fabro et al., op. cit. (1965).
b/ Kennedy et al., op. cit. (1968).
-------
at the same dose level produced young which exhibited mild to severe limb
abnormalities, attesting to the sensitivity of the two rabbit strains
employed.
The only work reported for rabbits in which malformed fetuses were
observed is that of Mclaughlin et al. (1969).—' In this study, groups of
nine pregnant New Zealand white rabbits were given captan at dose levels
of 37.5, 75 or 150 mg/kg body weight per day from days 6 through 16 of
gestation. Thalidomide, used at the rates of 75 and 150 mg/kg body weight,
produced the usual teratogenic response. Captan at 75 mg/kg body weight
of the mother caused nine malformed individuals from 75 implantation sites
of six does. Among the malformations were deformed limbs, cleft lip, and
fused upper lip at the 75 mg/kg dosage. At the 37.5-mg/kg dosage the one
malformed individual was acephalic.
Dogs - Earl et al. (1974)2.' conducted a study of the effects of captan on
reproduction and the young of dogs. They fed three groups of dogs (five
per group), 15, 30 and 60 mg/kg/day of captan, respectively, throughout
the gestation period. They had a dog colony, not used in this study,
which consisted of 48 females. These dogs had the following reproductive
record. The percent that became pregnant was 87.5% (42 out of 48 females).
The average litter size was 4.8 pups. Two percent were born dead. There
were 5.17o resorptions. The following abnormalities occurred in 203 pups:
nine subcutaneous hemorrhages, one abdominal hemorrhage, two cerebral
edemas, two congestive kidneys, one subcutaneous edema, two front leg
terata, one cleft palate, and one short tail.
The control dogs in this particular study produced 6.6 pups per litter
and 107o were stillborn. Of the five dogs that received 15 mg/kg/day, only
two became pregnant and of the pups produced 18.2% were stillborn. One
pup had a single kidney. It was the investigator's experience that single
kidney occurred once out of 500 births in control dogs. All five dogs
became pregnant on the 30-mg/kg/day level. The average litter size was
6.8 pups. There were 20.6% stillborn. Three of the pups born alive had
abnormalities. Two pups had crooked tails and one had gastroschisis.
Five of the dozen bitches given the 60-mg/kg/day level of captan had pups.
_!/ Mclaughlin, J. P., E. F. Reynaldo, J. K. Lamar, and J. P. Marlaio,
"Teratology Studies in Rabbits with Captan, Folpet and Thalidomide,"
Toxicol. Appl. Pharmacol., 14:641 (1969).
2/ Earl, F. L., E. Miller, and E. J. van Loon, "Reproductive Teratogenic
and Neonatal Effects of Some Pesticides and Related Compounds in
Beagle Dogs and Miniature Swine," E. D. William and B. Deichmann,
Pesticides and the Environment, a Continuing Controversy, Intercon-
tinental Medical Book Corporation, New York, New York (1974).
65
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The average litter size was 4.4 pups. Only one pup was stillborn. One
pup had a dome-shaped skull and was hydrocephalic. One pup had an open
fontanelle; another pup had a single kidney.
When captan was administered in the diet of beagles at doses of 0,
30, or 60 mg/kg/day, either throughout gestation or throughout gestation
with an eight week lactation period, no signs of teratogenecity or embryo-
toxicity were noted. Survival of the pups during the lactation period was
not affected by captan (Kennedy et al.).!/.
Hamsters - In a study performed by Kennedy et al. (1968), groups of preg-
nant female hamsters were fed diets containing sufficient concentrations
of captan so that the animals received an average daily intake of 0, 125,
250, 500 and 1,000 mg/kg body weight from days 1 through 15 of gestation.
At day 15, all females were sacrificed, the young were surgically removed
and the fetal development and structural formation of each were examined.
As indicated in Table 9, the incidence of abnormal effects was not greater
in any test group than in the controls. A significant increase in fetal
resorption was observed at the dose level of 1,000 mg/kg body weight. The
following terata were observed in hamster fetuses by Kennedy et al. (1968):
Dose
level
(mg/kg)
125
250
500
1,000
Control
Finding
Total abnormal
Meningoencephalocele
Microphthalmia
Total abnormal
Microphthalmia
Developmental retardation
Total abnormal
Cranial blister
Exencephaly
Shortened forelimb
Gross developmental retardation
Total abnormal
Microphthalmia
Total abnormal
Microphthalmia
Caudal vertebrae absent
Absence of eye pigmentation
Facial hematoma
No skeletal structures present
Incidence
3.1
0.6
2.5
1.8
0.9
0.9
3.5
1.2
0.6
0.6
1.2
3.1
3.1
5.8
1.6
0.5
2.6
0.5
0.5
I/ Kennedy, GO. E. Fancher, and J. C. Calandra, "Tetratologic Evaluation
of Captan xn the Beagle Dog." unpublished report, Industrial Bio-Test
Laboratories, Inc., Northbrook, Illinois (undated)
66
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Table 9. TERATOGENIC ACTIVITY OF CAPTAN IN HAMSTERS
Species
Golden
Golden
Golden
Golden
Golden
Golden
Golden
Golden
Golden
Golden
Golden
Golden
Golden
Golden
Golden
Golden
Golden
hamster
hamster
hamster
hamster
hamster
hamster
hamster
hamster
hamster
hamster
hamster
hamster
hamster
hamster
hamster
hamster
hamster
Compound
Corn oil
(control)
Captan
Captan
Captan
Captan
None
Captan
Captan
Captan
Captan
Captan
Captan
Captan
Captan
Captan
Captan
Captan
Oral
dose
125*
250
500
1,000
—
2 , 500
1,500
1,000
500
1,000"^
750
600
500
400
300
200
Number
of Dosed,
pregnant gestational
females days
21
19 1-15
15 1-15
23 1-15
14 1-15
143
4 6-10
6 6-10
4 6-10
2 6-10
6 7 or 8
7 7 or 8
5 7 or 8
10 7 or 8
8 7 or 8
9 7 or 8
3 7 or 8
Total
number of
implantations
212
194
149
213
108
1,588
49
54
44
25
64
76
64
122
93
115
40
Average
number of
10
10
9
9
7
11
12
9
11
12
10
10
12
12
11
12
13
.1
.2
.9
.3
.7
.1
.2
.0
.0
.5
.7
.9
.8
.2
.6
.8
.3
Average
Number of litter
23 9.0
33
33
40
76
66
23
14
4
0
36
11
12
14
6
5
5
8.5
7.7
7.5
2.3
10.7
6.8
6.7
10.0
12.5
5.8
10.4
10.4
10.9
10.9
12.3
12.0
Number
of
normal
180
161
115
167
32
1,515
25
40
40
25
20
55
48
103
87
101
35
Number
of
11 a/
5
2
6
1
7 b/
1
0
0
0
8
10
4
5
0
9
0
* Daily intake.
~h Total dose administered as five small daily doses.
•f- Single dose.
a./ Kennedy et al., op. cit. (1968).
b/ Robens, op. cit. (1970).
-------
Using a slightly different approach, Robens (1970) compared the
teratogenic potency resulting from single administration with the com-
monly recommended multiple administration throughout organogenesis.
Captan at 200 to 1,000 mg/kg body weight was administered to pregnant
hamsters either on the seventh or eighth day of gestation or for five
consecutive days of gestation (days 6 through 10). Maternal mortality
resulted from many of these levels. Terata from single administration
included defects of the head, axial skeleton, limbs and viscera. As
was shown in Table 9, the most highly teratogenic levels, calculated as
percentage of implantation sites resulting in terata, was for captan at
1,000 mg/kg given as a single dose during the critical period of organo-
genesis (7 or 8 days). With multiple administration of each compound,
litters were apparently normal at the low levels, while at the high
levels maternal and fetal deaths and some decrease in fetal size occurred.
No anomalies, such as resulted from a single administration, were found.
Rats - The teratogenic activity of captan in rats was studied by Kennedy
et al. (1968). The results of feeding daily doses of 0, 50, 100 and 250
mg/kg body weight on days 6 through 15 of gestation and 500, 1,000 and
2,000 mg/kg body weight on days 8 through 10 of gestation are shown in
Table 10. No teratogenic effects were seen at any dose rate through
500 mg/kg body weight. Teratogenic effects were observed only at the
highest rates fed (1,000 and 2,000 mg/kg body weight). The terata ob-
served were in the form of subdermal hematomas and umbilical hernia.
One subdermal hematoma was observed in a control fetus. There was a
slight reduction in weight of the normal fetuses produced by rats fed
at the 2,000-mg/kg body weight level (4.5 g as compared with 4.8 g in
the controls).
Mice - A mouse study was reported in an abstract by Kennedy et al. (1972) .i/
Swiss white mice treated from gestation days 6 through 14 failed to show a
teratogenic response to captan doses up to 100 mg/kg body weight.
The U.S. Health, Education and Welfare Department (1969)2/ reported that
100 mg/kg captan in Dimethyl Sulfoxide (DMSO) caused an increase in the
proportion of abnormal litters and proportion of abnormal fetuses per litter
in the C57BL/6 mouse. The level of statistical significance was .01. When
captan was given to the same strain of mouse in honey or when given in DMSO
to the AKR mouse, no anomalies were noted at 100 mg/kg.
17 Kennedy, G. L. , J. F. Vondruska, 0. E. Fancher, and J. C. Calandra,
"The Teratogenic Potential of Captan, Folpet, and Difolatan "
Teratology. 5:259 (1972).
2/ U.S. Health, Education and Welfare Department, "The Report of the Secretary's
Commission on Pesticides and their Relationship to Environmental Health "
Table 1, p. 670-671; Table 3, p. 673 (December, 1969). '
68
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Table 10. TERATOGENIC ACTIVITY OF CAPTAN IN RATS
Compound
Corn oil
(control)
Corn oil
(control)
Captan
Captan
Captan
Captan
Captan
Captan
Oral
dose
(mg/kg)
500*
500
50
100
250
500
1,000
2,000
Number
of
pregnant
females
10
7
6
7
5
5
5
5
Dosed,
gestational
days
6-15
8-10
6-15
6-15
6-15
8-10
8-10
8-10
Total
number of
implantations
126
80
79
86
49
58
63
60
Number of
resorptions
3
2
2
4
4
10
4
0
Average
litter
size
12.3
11.1
12.8
11.7
9.0
9.6
11.8
12.0
Number
of
normal
fetuses
122
78
77
82
45
48
56
58
Number
of
terata
1(0.
0
0
0
0
0
3(5.
2(3.
8%)
17.)
3%)
* Daily oral dose.
Data from Kennedy et al., op. cit. (1968).
-------
Avian Embryotoxicity Verrett et al. (1969)1' states that, "captan is
indeed teratogenic in the developing chicken embryo." In this study,
captan was injected directly into either the yolk or air cell of fresh
fertile eggs at dose levels ranging from 0 to 20 ppm. Of a total of
1,292 eggs injected, 101 malformations (7.81% of total) were observed.
Of the 101 abnormalities observed, 26 were in the head region, 31 in
wing structure, 19 in leg structure, and 25 malformations of the lower
body. Although it is concluded that captan is highly teratogenic, these
studies were performed by egg injection and are atypical with respect to
absorption of captan through the egg membrane during egg formation in the
chicken. Actual feeding studies with captan (Verrett et al., 1969) indi-
cate that captan is not absorbed through the egg shell membrane during
egg production and no teratogenic effects can be observed.
In one study a group of five male and 18 female white leghorn chickens
were fed a diet containing 0 or 2,300 ppm (equivalent to 75 mg/kg body
weight) technical captan for 6 weeks. The birds were observed for body
weight effects, food consumption, behavioral reaction, and egg production.
Eggs collected during days 29 through 39 were incubated to determine the
extent of hatchability and the presence of any effects on the chicks. No
adverse effects were noted (Palazzolo, 1966).±7
A summary of teratogenic studies reviewed in this section is given
in Table 11.
Behavioral Effects
The review of the literature did not reveal any reports on adverse
behavioral effects of captan.
Toxicity Studies with Tissue Cultures
Legator et al. (1969)—' made a study of the mutagenic effects of captan.
In this study, cell growth was evaluated. A heteroploid human embryonic
cell line L/32 was used. Only a slight reduction of growth was obtained
with 3 ppm captan. At the 4-jig/ml level, growth was severely inhibited for
the initial 48 hr. After 48 hr, the cells recovered from captan treatment.
Mutagenic Effects
The Durham and Williams (1972) report has been used as the basis for
this section dealing with investigations of captan's mutagenic effects.
I/ Verrett, M. J. , M. K. Mutchler, W. F. Scott, E. F. Reynaldo, and
J. Mclaughlin, "Teratogenic Effects of Captan and Related Com-
pounds in the Developing Chicken Embryo," Ann. N. Y. Acad Sci
160:334-343 (1969). L
2/ Palazzolo, R. , Report on Captan, Industrial Bio-Test Laboratories,
unpublished report, Northbrook, Illinois (1966).
_3/ Legator, M. S., F. J. Kelly, S. Green, and E. J. Oswald, "Mutagenic
Effects of Captan," Ann. N. Y. Acad. Sci. . 160:34^-351 (1969).
70
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Table 11. SUMMARY OF TERATOGENIC INVESTIGATIONS WITH CAFTAN
Test animal
Results
Reference
Monkey
Monkey
Rabbit (NZ)+
Rabbit (DB)*
Rabbit (NZ) +
Rabbit
Dog
Dog
Hamster
Hamster
Rat
Mouse
Mouse
Chicken
No fetal abnormalities or abortions when dosed with 10-75 mg/kg captan on days 21-34 of
gestation.
No fetal abnormalities when dosed with 6.25-25 mg/kg captan on days 22-32 of gestation.
Fetal mortality in three of seven monkeys at 25-mg/kg level.
No fetal abnormalities with 80 mg/kg captan on days 7-12 of gestation. Four resorptions
of 43 implantations (no significant difference compared to control).
No fetal abnormalities with 75
43 implantations.
captan on days 6-16 of gestation. One resorption in
No fetal abnormalities with 18.75-75.0 mg/kg captan on days 6-18 of gestation. Thirty-
three resorptions in 39 implantations at 75 mg/kg.
Nine malformed individuals from 75 implantation sites at dose level of 75 mg/kg. Malfor-
mations included deformed limbs, cleft lip, and fused upper lip.
Daily captan dosage throughout gestation was 15, 30, or 60 mg/kg. 15 mg/kg gave 18.2%
stillborn and one abnormality; 30 mg/kg gave 20.6% stillborn and three abnormalities; 60
mg/kg gave 4.5% stillborn and three abnormalities.
Captan, up to 60 mg/kg/dog throughout gestation produced no signs of teratogenicity or
embryotoxicity
Incidence of terata in test groups (125-1,000 mg/kg on gestation days 1-15) no higher than
control group. Resorption incidence increased significantly at 1,000
Single captan injection of 750 and 1,000 mg/kg on day 7 or 8 of gestation gave 13.7 and
22.9% fetal abnormalities, respectively Respective fetal resorptions were 17.1 and 57.8%.
Multiple administration of 100-500 mg/kg/day on days 6-10 of gestation gave only one terata
at highest dose. Resorption rate increased with dose.
No fetal abnormalities at dosages 50-250 mg/kg on gestation days 6 to 15. At 1,000 and
2,000 mg/kg on gestation days 8-10, 3.3 and 5.1% terata occurred, respectively.
Captan levels up to 100 mg/kg on gestation days 6-14 showed no teratogenic response.
100 mg/kg captan in DMSO, produced terata in one species while the same dose in DMSO
to another species was negative; captan in honey was also negative.
Injection of captan into egg yolk or air sac at up to 20 ppm resulted in 101 abnormal-
ities (7.8% of total). Feeding captan to chickens resulted in no terata.
* DB - Dutch belted.
+ NZ - New Zealand white.
al Vondruska et al., op cit. (1971).
b_/ Courtney (1968). Quoted in Anon. , FAO/WHO report, op. cit.. (1970).
£/ Fabro et al., op. cit. (1965).
d_/ Kennedy et al. , op. cit. (1968).
e/ McLaughlin et al., op. cit. (1969).
f/ Earl et al., op. cit. (1974).
£/ Kennedy et al., op. cit. (1972).
h/ Robens, op. cit. (1970)
i/ Kennedy et al., op. cit. (1972).
j_/ U.S. Health, Education and Welfare Department, op. cit. (1969).
k/ Verrett et al., op. cit. (1969).
f/
JBL/
I/
V
il
k/
71
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Mutagenesis is defined as the study of mutations or an inherited change
in the genetic material of an organism. The change may be a chemical trans-
formation of a gene so that its function is altered, or it may be a chromo-
somal alteration. The mutations of most interest are those transmitted by
way of sperm or ovum to the next generation. Roughly, the methodology can
be divided into four categories:
1. Submammalian tests
a. Bacterial
b. Neurospora spp.
c. Drosophila spp.
2. Cytogenicity of mammalian cell culture
3. Host-mediated assay test
4. Mammalian tests
a. Specific locus test
b. Dominant lethal test
There are a number of opinions as to what type of test should be used
to estimate mutagenesis. Epstein (1970)JL' felt that submammalian systems
were not of great value. Epstein and Shafner (1968)—' advocated the dominant
lethal test.
Durham and Williams (1972) quoting Jacobson (1971) reported that 275
chemicals had been tested for mutagenicity by the dominant lethal test, and
seven gave positive results. One hundred compounds had been evaluated by
the host-mediated assay, and six positive results were obtained.
Legator (1970)2' addressed the value of mutagenicity tests by listing
some contributions from the Food and Drug Administration research: (1) char-
acterization of the natural occurring mycotoxin (aflatoxin) as a mutagenic
agent; (2) determination of the in vivo cytogenetic effects of cyclohexylamine,
a metabolite of cyclamate; (3) characterization of captan as a mutagenic
agent; and (4) the induction of the dominant lethal effects of DDT. These
compounds reveal an interrelationship between mutagenic, carcinogenic, or
teratogenic effects. Aflatoxin is teratogenic, carcinogenic, and mutagenic.
Cyclamate has been shown to induce bladder tumors. Captan is teratogenic
in laboratory animals, and DDT produces tumors in animals. Legator stated
that carcinogenic agents are usually mutagenic, but the converse is not
always true.
II Epstein, S. S., "Control of Chemical Pollutants," Nature, 228:816-819 (1970)
2J Epstein, S. S., and H. Shafner, "Chemical Mutagens in the Human Environ-
ment," Nature, 219:385-387 (1968).
3/ Legator, M. S. , "Chemical Mutagenesis Comes of Age," J. Hered 61(5)-
239-242 (1970). '
72
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Legator et al. (1969) evaluated the mutagenic activity of captan in
bacteria. The bacteria used in the study were Escherichia coli SD4-73
strains. The bacteria were grown for 24 hr in an aerated broth culture,
supplemented with 100 ug of streptomycin per milliliter. The washed
cells were added to soft agar; and the seeded layer was added to 15 ml of
a 2% nutrient agar base with and without the antibiotic. A small disk
was placed on the surface of the media and moistened with dimethyl
sulfoxide containing the test chemical. With the concentration of 250 ug
per assay disk, the mutants were increased sixfold. When the concentra-
tion of captan was raised to 1,000 ug per disc a tenfold increase of
mutants occurred over the control. An E. coli thymine-dependent strain
was used as a test organism and 1,000 ug of captan per assay disk brought
about a tenfold increase in the mutants over the control.
Ficsor and Nii Lo Piccolo (1970a and 1972)1_2_?_/ tested 14 pesticides
purchased from a hardware store for mutagenicity in E. coli and Salmonella
typhimurium. Two of the pesticides were mutagenic and both of them con-
tained captan (157° and 57°). Their test procedure was a rather simple one,
about 1 to 2 x 10^ bacteria were plated on minimal plates. The plates
were dried and spotted with pesticides and the mutagen nitrosoguanidine.
Among the strains tested cys B-12 in S. typhimurium responded with the
highest frequency of reversions.
Ficsor and Nii Lo Piccolo (1970b).£' made a study of the effect of
heating to sterilization temperatures on captan mutagenicity. They used
JL. coli- and cys mutant of S. typhimurium. The heat treatment of the
pesticide was accomplished by making a 1:10 suspension of the pesticide
in sterile distilled water. The suspension was divided into three parts:
(1) to stand at room temperature; (2) steam sterilization for 15 min,
which is about 100°C; and (3) autoclaved 15 min at 15 Ib pressure. In
the latter situation the temperature rose to about 121°C. After cooling,
the pesticides were placed on the plates, and reverted colonies were
counted. In the lac mutant the autoclaved pesticide induced 21 times
fewer reversions than the pesticide kept at room temperature. The steam-
sterilized pesticide induced five times fewer reversions than the room
temperature check.
j./ Ficsor, G., and G. M. Nii Lo Piccolo, "Captan-Induced Reversions of
Bacteria," Newlett. Environ. Mutagen. Soc., 3:38 (1970a).
_2/ Ficsor, G., and G. M. Nii Lo Piccolo, "Survey of Pesticides for
Mutagenicity by the Bacterial-Plate Assay Method," Environ. Mutagen.
Soc., 6:6-8 (1972).
_3/ Ficsor, G., and G. M. Nii Lo Piccolo, "The Effect of Temperature on
the Mutagenicity of Captan," Environ. Mutagen. Soc., 3:38 (1970b).
73
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Mailing and deSerres (1970)— tested captan on Neurospora crassa in
a series of pilot experiments to see if they could induce forward muta-
tions in the ad-3 region of a two-component heterokaryon and reverse
mutations in a series of test strains. They were able to obtain positive
evidence of mutagenesis of captan in the forward mutation system, but not
in the reverse mutation system.
Siebert et al. (1970)^ used Saccharomyces cerevisiae to test 14
fungicides for genetic activity. Their test system involved the induc-
tion of mitotic gene conversion at two different loci and cytoplasmic
respiratory deficient mutants. Captan was found to be a weak agent for
involving mitotic gene conversion and did not induce cytoplasmic mutation.
Clarke (1971)3/ used a mutational system of reversion to tryptophan
independence in the Escherichia coli B/r ochre auxotrophic mutant WWP-2.
Both the repair competent and excision repair deficient derivatives of
this strain were used in an effort to determine whether or not the muta-
genic activity of a pesticide was dependent on excision repair. Three
formulations of captan were tested. These chemicals markedly brought
about mutagenic activity causing an approximate 20-fold increase in
revertant numbers in the excision repair competent strain and approxi
mately 100-fold in the excision repair deficient strain.
Bridges et al. (1972a)4_/ worked with a number of repair-deficient
strains of Escherichia coli. These strains provided a sensitive assay
system for the mutagenic activities of chemicals and also permit useful
information to be obtained about the characteristics of the mutagenic
process. Using the various strains in simple spot testing experiments,
they observed mutagenic actions occurring in five strains. They showed
that a substantial part of the mutagenic activity of the fungicide cap-
tan is due to excisable DNA damage mediated by a volatile breakdown
product. They felt that the mutagenic properties of captan are in
essence those of one or more alkylating agents.
JL/ Mailing, H. V., and F, J. deSerres, "Captan--A Potent Fungicide with
Mutagenic Activity," Environ. Mutagen. Soc., 3:37 (1970).
2/ Siebert, D., F. K. Zimmermann, and E. Lemperle, "Genetic Effects of
~ Fungicides," Mutat. Res., 10:533-543 (1970).
37 Clarke, C. H. , "The Mutagenic Specificities of Pentachloronitrobenzene
and Captan, Two Environmental Mutagens," Mutat. Res., 11(2):247-248
(1971).
kj Bridges, B. A., R. P. Mottershead, M. A. Rothwell, and M. H. L. Green,
"Captan Mutagenesis of Repair-Deficient Strains of Escherichia coli,"
Environ. Mutagen. Soc., 6:9 (1972).
74
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Seller (1973)I/ made a survey of some 30 pesticides for their pro-
pensity for mutagenesis. They made their evaluations in five different
strains of Salmonella. Captan proved to be mutagenic in two of these
strains. The rating given by the authors was 2+ which they considered
medium. Captan has been shown to be a mutagenic substance through its
alkylating potency (Legator, 1969; Clarke, 1971). Investigations have
failed to disclose the similar effect in Drosophila (Mollet, 1973)!/
as well as in the dominant lethal test in mice (Anon., FAO/WHQ report,
1970, quoting Arnold, 1967).
Buselmaier et al. (1972)I/ evaluated 16 chemicals in host-mediated
and dominant lethal tests. None of the compounds proved to be mutagenic
in the dominant lethal test. Captan was definitely mutagenic in the host-
mediated assay.
Kramers and Knaap (1973)^./ investigated the mutagenic effects of
captan in Drosophila melanogaster. They administered pure captan by
injection into the abdomen of 4-day-old males (approximately 0.2 ug/ml)
or by continuous feeding of larvae from the first instar until the adult
stage. They checked three types of induced genetic damage: (1) complete
and mosaic sex-linked recessive lethal mutations in male germ cells;
(2) II to III translocations in male germ cells; and (3) dominant lethal
mutations in male and female germ cells. In the sex-linked recessive
tests, the frequency obtained in the captan series appeared to be rather
high, but the pooled data (19 lethals in 4,360 chromosomes tested) did
not differ significantly at the 570 level from the control (pooled 24
lethals in 9,155 chromosomes tested). No translocations were found in
the total of 1,271 gametes after a larval feeding of captan at concentra-
tions of 0.3 and 17o. And none were observed in the total of 2,172
gametes tested after injection of the same substance. No evidence was
produced to indicate the induction of dominant lethal mutations. They
concluded that their results failed to demonstrate mutagenic activity of
captan under the conditions employed although the possibility was not
ruled out that a very mild effect may exist. The investigators' inter-
pretation was that possibly captan is destroyed before it reaches the
gonads in an effective concentration.
ITSeiler, J. P., "A Survey on the Mutagenicity of Various Pesticides,"
Experientia, 29:622-623 (1973)
2J Mollet, P., "Untersuchungen uber Mutagenitat and Toxizitat von Captan
~ bei Drosophila," Mutat. Res.. 21:137-138 (1973).
3/ Buselmaier, W., G. Rohrborn, and P. Propping, "Mutagenitats-Unter-
suchungen mit Pestiziden im Host-mediated assay und mit dem
Dominanten Letaltest an der Maus," Biol. Zbl., 91:311-325 (1972).
4_/ Kramers, P G. N., and A. G. A. C. Knaap, "Mutagenicity Tests with
Captan and Folpet in Drosophila melanogaster," Mutat. Res., 21:
149-154 (1973).
75
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Mollet (1973) tested captan for its mutagenicity in adult males of
Drosophila melanogaster. He determined mutagenicity from the frequency
of sex-linked recessive lethal in pre- and post-meiotic germ cells. It
was found that captan was not mutagenic at low nontoxic or at high toxic
concentrations. Even in combination with the solvent dimethyl sulf oxide,
captan was not mutagenic. The results were explained by the assumption
that captan is inactivated before it reaches the germ cells.
Legator et al. (1969) evaluated the mutagenic activity of captan in
a cell line derived from human embryonic lung cells and from the kidney
of the kangaroo rat.
The embryonic lung cell line was a heteroploid human embryonic cell
line L-132. Growth was reduced slightly by 3 ug/ml of captan. At the
4-jig/ml level minimal growth occurred up to 48 hr. After 48 hr, the cells
recovered from captan treatment. When the concentration was in excess of
5 ug/ml, no growth occurred. It is noteworthy that 100 pg/ml of tetrahydro
phthalimide and phthalimide were nontoxic. Initial inhibition of mitosis
by captan at the time of incubation was found at 3 and 4
Chromosome studies were made and the procedure was the same for
mitotic inhibitions. The cells were exposed to captan after 40 hr of
incubation. After the addition of captan, cells were removed and meta-
phase cells examined for chromosome effects. There appeared to be
increases in breaks in 2 to 4 hr after the addition of captan and the
increase persisted through 24 hr. These breaks were mainly of the
chromatid type with a few exchange figures found in the 24-hr time
interval.
The kangaroo rat cell line was grown in mono layer cultures, at 37 °C
in an atmosphere of 3% carbon dioxide. After 16 hr exposure to 1 jig/ml
captan, there was approximately 3% mitosis; 5 ug/ml produces 1% mitosis.
The percentage of chromosome breaks rose from 10% at 1 ug/ml of captan to
70% at 10 ug/ml of captan.
Epstein and Shafner (1968) studied the mutagenicity of a wide variety
of environmental pollutants using mice as a screening element. In general,
the LD5Q doses were selected for testing and they rated the reaction of the
chemicals in terms of a mutagenic index (MI) . This index reflected the
incidence of dominant lethal mutations, and was calculated by the following
formula:
MT = deciduomata + late deaths ,nn
total implantations * 1UU'
Captan was evaluated at two dosage levels (500 and 9 mg/kg) , and it was
administered both intraperitoneally for low doses, and orally for higher
doses. They bred 21 females in one instance and 18 in another, and the
percentage pregnancies were 95% and 83%, respectively. The average number
of implants were 10.5 and 11.4. The MI values for captan were in the con-
trol range.
76
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A number of structurally related compounds, captan, captafol, folpet
and thalidomide were studied in two types of mutagenic tests: the dominant
lethal study in mice and the host-mediated assay in rats using a histidine
auxotroph of Salmonella typhimurium (Kennedy et al) .—' Doses of captan in
the dominant lethal study were 3 and 6 mg/kg injected IP once and in the
host-mediated assay, 125 and 250 mg/kg by intubation for 14 days. None of
the compounds were positive in either test system.
Captan, 3.5 or 7.0 mg/kg, was injected into male mice prior to mating
with untreated females. One positive control was methylmethane sulfonate,
while actinomycin D was also used as a positive control, since it has been
reported to induce chromosomal breaks in vitro similar to those seen with
captan (Arnold et al. 1967)^:/. No dominant lethal mutations were noted.
3/
Collins (19723)—' injected technical grade captan into male rats
and mice. The administrations were given either intraperitoneally IP in
doses of 2.5, 5.0, or 10.0 mg/kg/day for 5 days or by oral intubation
doses of 50, 100, or 200 mg/kg/day for 5 days. An increase in the mean
number of early fetal deaths per pregnancy was seen in rats during the
first 7 weeks after IP administration of captan at the highest dose
level, but this increase was not statistically significant. Similar
effects were obtained with intubation. There were increases in the
mean number of early deaths at all dose levels but were statistically
significant only after the fourth week after intubation with 100 mg/kg/
day and weeks 1, 2, and 5 with 200 mg/kg/day. Mutagenic damage appeared
to be slight. Mutagenic effects as measured by the increase in the
mean number of early fetal deaths per pregnancy were visible in mice
after IP treatment of captan at the highest dose level for the first
7 weeks after implantation. But the increase was only significant for
weeks 4 and 5. Increases were notable at the highest dosage levels for
the first 5 weeks after oral intubation of captan, but no statistically
significant increases were found after the second week. At all levels
of IP treatment, captan produced no significant increase in the percent-
age of litters with one or more early deaths and only one significant
increase in the percentage of the litters with two or more early deaths.
With oral intubation, similar results were obtained. Even at the highest
dose levels of intraperitoneal or orally administered captan no dominant
lethal mutants were detected by any decrease in total implantations per
pregnant female.
_!/ Kennedy, G., D. Arnold and M. Keplinger, "Mutagenic Studies with Captan,
Captofol, Folpet and Thalidomide," unpublished report, Industrial
Bio-Test Laboratories, Northbrook, 111. (undated).
_2/ Arnold, D., R. Kodras, and 0. Francher, "Mutagenic Study on Captan,"
unpublished report by Industrial Bio-Test Laboratories for Chevron
Chemical Co., Richmond, Calif. (1967).
3/ Collins, T. F. X., "Dominant Lethal Assay. I. Captan." Food Cosmet.
Toxicol., 10:353-361 (1972a).
77
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A summary of the investigations of the mutagenic effects of captan
is presented in Table 12.
Oncogenic Effects
It is advisable that the route of the administration for the testing
of chemicals for carcinogenesis should be by the same exposure route as
used for humans, for example, as in exposures from residues and food
(Durham and Williams, 1972).
Steckerl and Turner (1965)!/ had found in early experiments that the
extracts of seeds inhibited the development of mouse ascites carcinoma
and this inhibitory action had been traced to the presence of captan,
which had been used as a seed treatment. These investigators injected
white Swiss mice with 0.15 g/kg of captan intraperitoneally for 14 days,
and these animals had been inoculated 1 day before injection with 2 x 10°
ascites tumor cells. Dosages of captan above this level were found to
be too toxic. The mean survival of mice inoculated with ascites tumor
cells was increased from 26 to 80 days by the injection of the captan.
They also noted that all the mice treated with captan, on autopsy, had
solid masses apparently originating from the injection site in the
abdominal wall. No histopathological examination of the masses was made.
Innes et al. (1969) investigated the tumorigenicity of 130 compounds
in mice. They used two hybrid strains of mice of both sexes with 18
animals per group. Maximum tolerated doses were either administered by
single subcutaneous injection or continuous oral administration. For
their tumorigenicity test, the dose was given by stomach tube beginning
when the mice were 7 days of age. The same absolute amount of each com-
pound was given each day until the mice were 4 weeks old. Captan was
given at a daily dosage of 215 mg/kg in a vehicle which is equivalent to
about 560 ppm in a 0.5% gelatin vehicle. The dose was not adjusted
according to weight. As the mice were weaned at 4 weeks of age, captan
was added directly to the diet at 560 ppm. No vehicle was used when
captan was fed in the diet. The test ran for 18 months, and there was
no significant increase in tumors in the animals fed captan as compared
with the controls.
Swiss white mice were fed technical captan at doses of 0, 3,750 or
7,500 ppm in the diet which approximated 0, 560 or 1050 mg/kg/day.
N-Nitroso diethylamine (10 ppm) was the positive control. The positive
control caused focal hyperplastic changes in the livers of both sexes
and neoplastic lesions in the liver, lung and forestomach of the females.
Captan did not cause any gross or microscopic changes nor did it cause
increased mortalities. Other parameters besides histology and gross
observations were not measured. (Reyna et al. 1973),2J
I/ Steckerl, F. , and M. L. Turner, "Effect of Captan on the Mouse Ascites
Tumor of Ehrlich," Nature. 206:839 (1965).
27 Reyna, M. , G, Kennedy, and M. Keplinger, Eighteen-Month Carcinogenic
Study with Captan Technical in Swiss White Mice, unpublished report,
Industrial Bio-Test Laboratories, Northbrook, 111. (April, 1973).
78
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Table 12. SUMMARY OF MUTAGENIC INVESTIGATIONS WITH CAFTAN
System
Organism or tissue
Results
Reference
Bacteria
Yeast
Tissue
culture
Escherichia coli
SD4-73 strains
Escherichia coli
NG 422 and YA 482
Salmonella ty phimur ium
CYS_-(CYS B12)
LEU-CAP 517, 5BU 504)
Neurospora crassa
Neurospora crassa
Escherichia coli
B/r ochre auxotrophic
Mutants WWP-2 (her+ and her-)
Escherichia coli
WP2 TRP (ochre)
WP2 uvrA, CM 561 exrA. CM 571
recA, CM 611 uvrA. exrA
Salmonella strains
G46, TA1530, TA1531, TA1532,
TA1534
Salmonella typhimurium G46 His-
Salmonella typhimurium G46 His-
Saccharomyces cerevisiae
Diploid strain DY
Haploid MA20: a, ga!2, ade2-2,
trp5-12 leul; MD 20: a +,
ade2-I, trp5-27 - +
Embryonic lung cell human L-132
Rat kangaroo cell line
Drosophlla Drosophila melanogaster
Drosophila melanogas ter
Mice Mice, NMRI strain
Swiss mice, CD-I
CR Mice
Swiss white mice
Mice and Osborne Mendel rats
rats CBA-J mice
Mutations were observed aj
Mutagenic b/
Mutagenic cj
Mutagenesis in forward mutation system d_/
None in reverse mutation system d/
Markedly mutagenic in excision repair e/
deficient and competent strain
Mutagenesis occurred in five strains f/
Mutagenic in two strains
Mutagenic in host-mediated assay
Nonmutagenic in host-mediated assay h/
Weak agent for inducting mitotic gene il
conversion
No induced cytoplasmic mutation
Above 5 mg/ml no growth occurred a/
Break in chromosomes occurred
Mitosis resumes at 1 ug/ml; 70% chromo- a./
somes break at 10 ug/ml
Failed to demonstrate mutagenic activity j_/
using sex-linked recessive lethal,
II-III translocations and dominant
lethal tests
No mutagenic effects by sex-linked k/
recessive lethal tests
Nonmutagenic in dominant lethal test _!/
Mutation index (dominant lethal test) 37
same as controls m/
Nonmutagenic in dominant lethal test n/
Nonmutagenic in dominant lethal test oj
No dominant lethal mutants were detected p_/
a/ Legator et al., op. cit. (1969).
b/ Ficsor and Nii Lo Piccolo, op. cit. (1970a).
£/ Ficsor and Nii Lo Piccolo, op. cit. (1972).
d/ Mailing and deSerres, op_. cit. (1970).
_e/ Clarke, op. cit. (1971).
f/ Bridges et al., ££. cit. (1972).
£/ Sailer, op_. cit. (1973).
h/ Kennedy et al., Industrial Bio-Test Laboratories, unpublished report, op. cit.
17 Siebert et al. , op_. cit. (1970).
j_/ Kramers and Knaap, op. cit. (1973).
k/ Mollet, o£. cit. (1973).
I/ Buselmaier et al. , op_^ c±t_. (1972).
m/ Epstein and Shafner, op. cit. (1968).
n/ Kennedy et al., Industrial Bio-Test Laboratories, unpublished report, op. cit.
£/ Arnold et al., op. cit. (1967).
£/ Collins, op_. cit. (1972a).
79
-------
In a chronic study!/ with rats of 104 weeks duration, 10 female and
10 male rats were placed on each of four diets, basal, basal plus 0.1%
captan, basal plus 0.5% captan, and basal plus 1.0% captan. At the 24th
week half of the animals were placed on 1% recrystallized captan. At the
time of death or sacrific the following observations were made:
Diet Tissue Abnormalities
Control 1 Male - Intragastric fibroma-ulcerating
1 Female - Adeno fibroma - breast
0.1% Captan 1 Male - Benign liver hepatoma
1 Female - 2 Benign cystic breast tissues
1 Benign papillary cyst adenoma
1 Breast adenoma
0.5% Captan 1 Male - Interstitial adenoma of the testes
1 Male - Benign liver hepatoma
4 Females - 1 Benign liver hepatoma
1 Benign hurthe cell adenoma thyroid
2 Hyperplastic breast tissues
2 Benign papillary cyst adenofibromas
of the breast
Diet 1 Benigh fibroma or reticular cell tumor -
marked hyperplasia and malignant potentialities
1 Lutein cyst of ovary
1 Benign fibroma
1.0% Captan None
Preliminary data indicates an increase in lung tumors in female Swiss
mice receiving 11 doses of approximately 20 mg/kg captan for 22 days. Captan
was administered either intraperitoneally or by gavage (Rosenkranz, 1974)±A
Effects on Man
There was little information available on the acute and subacute
toxicity of captan, the symptoms of its poisoning, dermal and inhalation
effects, the occupational hazards posed by the use of captan in crop
application, and the hazards that might be involved in its manufacture.
One study in an article by Durham and Williams (1972) cites an Idaho
Pesticide Community Study, EPA. The study reported no lymphocyte chormosome
abberations could be attributed to captan among workers in a formulation
plant.
I/ Captan Reports, EPA Pesticide Petition Nos. 15 and 124, Section C.
2J Rosenkranz, H. S., Department of Microbiology, Columbia University, N.Y.C,
personal communication (1974).
80
-------
Accidents involving captan, however, have been more fully reported.
Preliminary data from the EPA Pesticide Accident Surveillance System (PASS)
show that captan was cited in 33 episodes (involving humans, animals, and
plants as well as area contamination) for the period of 1972 through
January 1974. Eleven of these cases were reported for 1973 (captan was the
39th most frequently cited pesticide for 1973).
The available accident data does not establish a pattern between cap-
tan and any specific use. Ten of the 33 reported episodes, however, did
involve possible intoxication of children from home and garden products
(treated flowers and vegetable seeds, tomato dust, etc.).
Summary
Reproduction - In reproductive studies with rats, as much as 1,000 ppm
of captan was fed through to two generations (two litters per generation)
without any effect on fertility, gestation, viability or lactation indices.
In the third generation, the lactation index was suppressed slightly.
When captan was given in daily doses of 6 to 57 mg/kg, sperm motility
was decreased. The same observation was made for mice (daily dosage 2.5
to 20 mg/kg). In another test, mice received 50 or 100 mg/kg for 5 days.
The fertility index was depressed at both levels. The weaning weights
were decreased in the first litter of the second generation.
Teratology - Single and multiple doses (200 to 1,000 mg/kg) of captan
have been given to pregnant hamsters on the seventh and eighth day or on
days 6 through 10 of gestation. Anomalies occurred after single dose ad-
ministration; 13.7% of the young were deformed at a dose level of 750 mg/kg
given on day 7. The dose resulted in 22% dam mortality. After a dose of 500
mg/kg was given on days 6 through 10 of gestation, the young were normal. At
higher levels, fetal death and small fetuses were observed, but there were no
anomalies.
In another test, hamsters were given 125, 250, 500 and 1,000 mg/kg of
captan each day for the first 15 days of gestation. There were no more
abnormal effects in the test group that received 1,000 mg/kg than in the
control group.
There have been two reports where rabbits received 80 mg/kg and 75
mg/kg during gestation (days 7 through 12 and days 6 through 16) and no
malformed fetuses were produced. Conversely, it has been reported that
nine malformed fetuses were found in 75 implants in nine pregnant rabbits.
In one investigation in rats, high levels of captan (50 to 500 mg/kg
body weight) did not produce a significant increase in the number of
abnormalities (395 fetuses were observed). Abnormalities were observed at
the next highest levels of 1,000 and 2,000 mg/kg.
No teratogenic effects were observed in monkeys receiving daily doses
of 6.25, 12.5 or 25 mg/kg of captan. Fetal mortality was high at the 25 mg/
kg level.
81
-------
An incidence of 7.81% malformations (of the total number of embryos
tested) has been observed in chick embryos where the eggs were injected
with 0 to 20 ppm of captan.
In tissue cultures, 4 mg/ml of captan severely inhibited growth for
48 hr. After that period, the cells recovered and normal growth ensued.
Mutagenesis - There are a number of investigations of mutagenic effects
of captan. Mutations have been observed in bacteria (Escherichia coli and
Salmonella typhimurium) and in fungi (Neurospora crassa and Saccharomyces
cerevisiae). Concentrations of 250 ;ig of captan in contact with
Escherichia coli produced a sixfold increase in mutants; a ten-fold
increase was produced by 1,000 jig.
Captan produced positive evidence of mutagenesis in the forward muta-
tion system and none in the reverse mutation system with use of Neurospora
crassa as a test organism.
In one investigation with Saccharomyces ceverisiae, captan was found
to be a weak agent for mitotic gene conversion and did not induce cyto-
plasmic mutation.
Captan has produced marked mutagenic activity in causing an approxi-
mate 20-fold increase in revertant numbers in the excision repair-
deficient strain and approximately 100-fold increase in the excision
repair competent strain using Escherichia coli B/r ochre auxotrophic
mutant WWP-2.
It has been shown that a substantial part of the mutagenic activity
of captan is due to excisable DNA damage mediated by a volatile breakdown
product.
In one investigation, captan did not bring about sex-linked recessive
lethal mutations, translocations or dominant lethal mutations in
Drosophila melanogaster. Another investigator reported that captan was
not mutagenic (sex-linked recessive lethal test) in Drosophila melanogaster.
It was assumed that captan was inactivated before it could reach the germ
cells.
Chromosome studies were made of a heteroploid human embryonic cell
line exposed to captan. There was an increase in breaks in 24 hr after
the addition of captan. The break persisted for 24 hr. The breaks were
mostly chromatid types. In a kangaroo rat cell line, the percentage of
chromosome breaks rose from 10% at 1 ug/ml to 70% at 10 ug/ml of captan.
Captan did not produce dominant lethal mutations when mice were
injected intraperitoneally (single) with 3.5 and 7.0 mg/kg of captan.
In other investigations with mice, the incidence of dominant lethal muta-
tions xvas in the normal range.
82
-------
Mutagenic effects have been observed in mice as measured by the
increase in the mean number of early fetal deaths per pregnancy after intra-
peritoneal injection into the male of 10.0 rag/kg (5 days) during the first
7 weeks after implantation.
At the highest dose levels of intraperitoneally or orally administered
captan, no dominant lethal mutants were indicated by a decrease in total
implantations per pregnant female.
Oncogenesis - It has been shown that captan injected intraperitoneally
increases the mean survival times of mice (from 26 to 80 days) that have
been inoculated with ascites tumor cells. In addition, all the mice treated
with captan were found to have developed solid masses at the site of
injection into the abdominal wall. A histological evaluation to classify the
observed masses as tumors was not made.
Captan has been administered to mice at a level equivalent to about
560 ppm in the diet for 18 months and there was no significant increase of
tumors over the controls.
Information on the effects of captan on man relative to acute and
subacute toxicity, and inhalation effects, or the possible occupational
hazards involved in application or manufacture is limited.
In an EPA Pesticide Community study of possible chromosomal aberrations
among workers in a captan formulating plant, no chromosomal damage was reported.
83
-------
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Collins, T. F. X., "Effect of Captan and Triethylenemelamine (TEM) on Re-
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287 (1972b).
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"The Fate of N-Trichloro[14C] methylthio-4-cyclohexene-l,2-dicarboximide
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Earl, F. L., E. Miller, and E. J. van Loon, "Reproductive Teratogenic and
Neonatal Effects of Some Pesticides and Related Compounds in Beagle Dogs
and Miniature Swine," E. D. William and B. Deichmann, Pesticides and the
Environment, a Continuing Controversy, Intercontinental Medical Book
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Engst, R., and M. Raab, "Zum Metabolismus fungizider Phthalimid-Derivate
in lebens - mittelchemischtoxikologischer Sicht," Nahrung, 17:731-738 (1973)
Epstein, S. S., "Control of Chemical Pollutants," Nature, 228:816-819 (1970).
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Epstein, S. S., and H. Shafner, "Chemical Mutagens in the Human Environment,"
Nature. 219:385-387 (1968).
Fabro, S., R. L. Smith, and R. T. Williams, "Embryotoxic Activity of Some
Pesticides and Drugs Related to Phthalimide," Food Cosmet. Toxicol., 3:
587-590 (1965).
FAO/WHO, "Captan," 1969 Evaluations of Some Pesticide Residues in Food,
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Farm Chemicals Handbook, Meister Publishing Company, Willoughby, Ohio (1970).
Ficsor, G. , and G. M. Nii Lo Piccolo, "Captan-Induced Reversions of Bac-
teria," Ne^sJ.ett_._J^iy2.r^nJ.^^ 3:38 (1970a) .
Ficsor, G. , and G. M. Nii Lo Piccolo, "The Effect of Temperature on the
Mutagenicity of Captan," Environ. Mutagen. Soc., 3:38 (1970b).
Ficsor, G. , and G. M. Nii Lo Piccolo, "Survey of Pesticides for Mutagenicity
by the Bacterial-Plate Assay Method," Environ. Mutagen. Soc., 6:6-8 (1972).
Fogleman, R. , Report of Hazelton Laboratories on Captan, EPA Pesticide
Petition No. 15, (1955).
Gale, G. R. , A. B. Smith, L. M. Atkins, E. M. Walkers, Jr., and R. H.
Gadsden, "Pharmacology of Captan: Biochemical Effects with Special
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426-441 (1971).
Gray, E., Report of Hazelton Laboratories on Captan, EPA Pesticide Petition
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Innes, J. R. M. , B. M. Ulland, M. G. Valerio, L. Petrucelli, L. Fishbein,
E. R. Hart, A. J. Pallotta, R. R. Bates, H. L. Falk, J. J. Gart, M. Klein,
I. Mitchell, and J. Peters, "Bioassay of Pesticides and Industrial Chemi-
cals for Tumorigenicity in Mice: A Preliminary Note," J. Natl. Cancer
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Johnson, D. F., "A Toxicity Test of n-Trichloromethylthiotetrahydrophthali-
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Hazelton Laboratories, Report on Captan, 1957, EPA Petition No. 124, amended.
Hoffman, L. J., J. R. Debaun, J. Knarr, and J. J. Menn, "Metabolism of N-
(trichloromethylthio)l, 2-dicarboximido 1^C-4-cyclohexene (Captan) in the
Rat," Stauffer Chemical Co., Westport, Conn. (August 1973).
Kennedy, G. , 0. E. Fancher, and J. C. Calandra, "An Investigation of the
Teratogenic Potential of Captan, Folpet, and Difolatan," Toxicol. Appl.
Pharmacol., 13:420-430 (1968).
Kennedy, G. , 0. E. Fancher, and J. C. Calandra, "Tetratologic Evaluation of
Captan in the Beagle Dog," unpublished report, Industrial Bio-Test Labora-
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85
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Kennedy, G. , D. Arnold, and M. Keplinger, "Mutagenic Studies with Captan,
Captofol, Folpet and Thalidomide," unpublished report, Industrial Bio-
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Kennedy, G. L., J. F. Vondruska, 0. E. Fancher, and J. C. Calandra, "The
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Kramers, P. G. N., and A. G. A. C. Knaap, "Mutagenicity Tests with Captan
and Folpet in Drosophila melanogaster," Mutat. Res., 21:149-154 (1973).
Krijnen, C. G., and E. M. Boyd, "Susceptibility to Captan Pesticide of Al-
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Food Cosmet. Toxicol., 8:35-42 (1970).
Krijnen, C. G. , and E. M. Boyd, "The Influence of Diets Containing from 0
to 81 Percent of Protein on Tolerated Doses of Pesticides," Comp. Gen.
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Legator, M. S., F. J. Kelly, S. Green, and E. J. Oswald, "Mutagenic Effects
of Captan," Ann. N. Y. Acad. Sci., 160:344-351 (1969).
Legator, M. S., "Chemical Mutagenesis Comes of Age," J. Hered., 61(5):239-
242 (1970).
Link, R. P., J. C. Smith, and C. C. Morrill, "Toxicity Studies on Captan-
Treated Corn in Pigs and Chickens," J. Am. Vet. Med. Assoc., 128:614-616
(1956).
McLaughlin, J. P., E. F. Reynaldo, J. K. Lamar, and J. P. Marlaio, "Tera-
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Fisheries and Wildlife, Special Scientific Report—Wildlife No. 127,67-
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Mollet, P., "Untersuchungen uber Mutagenitat and Toxizitat von Captan bei
Drosophila," Mutat. Res., 21:137-138 (1973).
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86
-------
Palmer, J. S., "Tolerance of Sheep to Captan," J. Am. Vet. Med. Assoc.,
143:513-514 (1963).
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87
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PART II. INITIAL SCIENTIFIC REVIEW
SUBPART C. FATE AND SIGNIFICANCE IN THE ENVIRONMENT
CONTENTS
Page
Effect on Aquatic Species 89
Fish 89
Laboratory Studies 89
Lower Aquatic Organisms 96
Laboratory Studies • • 96
Field Studies 98
Effects on Wildlife 99
Laboratory Studies 99
Field Studies 99
Effects on Beneficial Insects 100
Bees 100
Parasites and Predators 100
Interactions with Lower Terrestrial Organisms 103
Microflora 103
Microfauna 108
Residues in Soil 109
Laboratory and Field Studies ..... 109
Monitoring Studies „ HI
Bioaccumulation, Biomagnification 113
Environmental Transport Mechanisms 114
References 116
88
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This section contains data on the environmental effects of captan,
including effects on aquatic species, wildlife, and beneficial insects
and interactions with lower terestrial organisms. Captan residues in
soil are also discussed. The section summarizes rather than interprets
data reviewed.
Effects on Aquatic Species
Fish -
Laboratory studies - Toxicity of captan to fish has been studied
in some detail. The effects of captan on other aquatic organisms (with
the exception of Daphnia magna) have not been as thoroughly examined.
Acute toxicity data for fish in terms of Tiro's, LCso's, and single
concentration exposure tests are summarized in Table 13.
The acute toxicity of captan for zebrafish larvae was demonstrated
by Abedi and McKinley (1967)JY, who advocated the use of this species in
a bioassay for the fungicide. The I^Q determined in this study was
0.67 ppm (90 min).
The death of zebrafish larvae from captan poisoning was reported to
be always associated with an observable head injury in which the eyeballs,
while still retaining connection with the optic tissues, appeared to be
blown out of the sockets and the head was ruptured into lateral halves
to give a bicephaleous appearance. The head injury reported for zebrafish
larvae during captan poisoning is considered to be a specific response of
this species (Abedi and McKinley, 1967; Abedi and Turton, 1968)2/. Captan
has not been reported to exhibit this toxicity effect for other fish.
Nishiuchi and Hashimoto (1969)!/ have reported the TLm (median
tolerance limit) for a 48-hr exposure to be 0.25 ppm for the common carp
and 0.037 ppm for the goldfish.
Rainbow trout were reported by Holland et al. (I960)—' to exhibit 50%
mortality when exposed to captan for 72 hr at a concentration of 0.16 ppm
in aerated freshwater. The smaller specimens were not as susceptible as
were the larger (2.8-in. versus 4.8-in. trout), at an equal concentration
of captan, but the condition of the smaller fish at the end of the experi-
ment indicated that some damage was produced at less than 0.32 ppm captan.
I/ Abedi, Z. H., and W. P. McKinley, "Bioassay of Captan by Zebrafish
Larvae," Nature (London), 216:1321-1322 (1967).
2J Abedi, Z. H., and D. E. Turton, "Note on the Response of Zebrafish
~~ Larvae to Folpet and Diofolatan," J. Assoc. Off. Anal. Chem., 51:
1108-1109. (1968).
3/ Nishiuchi, Y., and Y. Hashimoto, "Toxicity of Pesticides to Some Fresh-
water Organisms, "Rev. Plant Protec. Res., 2:137-139 (1969).
4/ Holland, G. A., J. E. Lasater, E. D. Neuman, and W. E. Eldridge, "Toxic
Effects of Organic and Inorganic Pollutants on Young Salmon and
Trout," Department of Fisheries Resource Bulletin No. 5, Washington,
B.C., 136-139 (1960).
89
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Table 13. TOXICITY OF CAFTAN TO FISH
Test species
Bluegills
Bluegills
Carp
Channel catfish
Coho salmon
Fathead minnows
Fathead minnows
Fathead minnows
Goldfish
Brook trout
Cutthroat trout
Lake trout
Lake trout
Rainbow trout
Rainbow trout
Zebraf ish
Sex and age
of animals
Fingerlings
Mixed sex,
1.5 months
Mixed sex,
young
Fingerlings
Fingerlings
Mixed sex,
3.5 months
Fingerlings
Mixed sex
Mixed sex,
young
Mixed sex,
1.5 months
Fingerlings
Fingerlings
Fingerlings
Fingerlings
Mixed sex ,
young
Mixed sex,
larvae
Toxicity
calculation
LC50 (96 hr)
TL50 (96 hr)
TI™ (48 hr)
LC5Q (96 hr)
LC50 (96 hr)
TL50 (96 hr)
LC50 (96 hr)
Toxicity, chronic
(45 weeks)
TLm (48 hr)
TL50 (96 hr)
LCso (96 hr)
LC50 (96 hr)
LCso (96 hr)
LC50 (96 hr)
72 hr toxicity
exposure
LC5Q (90 min)
Toxicity
measured
150 fig/1
72 jig/1
0.25 ppm
77.5^g/l
56.5 ug/1
65 ug/1
f
120 jig/1
Mortality at
29.5 and
63.5 ug/1
0.037 ppm
34 ug/1
48.5 ug/1
(x of 2)
51.0 ug/1
75.2 ug/1
102 jug/1
Mortality at
0.32 ppm
0.67 ppm
Comments
Static system
Flow-through system
-
Static system
Flow- through system
Flow-through system
Flow- through system
24% Mortality at 39.5
ug/1; 100% mortality
at 63.5 jig/1
-
Flow-through system
Static system
Flow-through system
Static system
Static system
50% Mortality at 32 ppm
-
Reference
b/
£/
I/
b/
b/
sJ
b/
a/
d/
sJ
y
b/
b/
b/
£/
£/
a./ Hermanutz, R. 0., L. H. Mueller, and K. D. Kempfert, "Captan Toxicity to Fathead Minnows
~~ (Pimephales promelas), Bluegills (Lepomis macrochinus), and Brook Trout (Salvelinus fontinalis),"
J. Fish Res. Board Can., 30:1811-1817 (1973).
_b/ United States Department of the Interior, Fish-Pesticide Laboratory, Columbia, Missouri, unpublished
data (1968-1972).
£/ Abedi and McKinley, op. cit. (1967).
d/ Nishiuchi and Hashimoto, op. cit. (1969).
~e/ Holland et al. , op. cit. (1960) .
-------
The lethal threshold concentration (LTC) is considered by some in-
vestigators to be a better measure of acute toxicity than is the 96-hr
TLcjg. However, as can be seen in Table 14, the data of the Hermanutz et
al. (1973) study shows good correlation (flow-through system) between the
two toxicity measurements for fathead minnow, bluegill, and brook trout.
In an extension of their study Hermanutz et al. (1973) also examined
the effect of static exposure to fathead minnows. Minnows placed in the
test tanks immediately after introduction of a static concentration of
550 ug of captan per liter died within 8 hr. A second group placed in
the same chamber 3 hr after introduction of the toxicant lived without
any apparent harmful effects (observed for 10 days) indicating that
breakdown of captan was rapid in the water used in these tests.
Mauck (1972)-i/ compared captan toxicity to several fish species
using two experimental water systems: (1) a static system and (2) a
flowing system. The results (Tables 15 and 16) indicated that in a
static system, where an initial level of captan might decrease with time
because of hydrolysis, etc., the toxic effect for fish diminishes rapidly.
For example, for Coho salmon, the 96-hr LC^Q in the static system was
137 ug/liter; but in a flowing system where the captan level was held
constant,the LC5Q was 56.5 ug/liter.
Hermanutz et al. (1973) studied captan toxicity to fathead minnows.
Growth and survival were not adversely affected by chronic exposure to
3.3, 7.4, or 16.8 ug of captan per liter of water. These relationships
are illustrated in Table 17.
Statistical evaluation of the data showed the maximum acceptable
toxicant concentration (MATC) to be between 39.5 and 16.8 ug/liter of
water. All but one of the fish died at a captan concentration of 63.5
Ug/liter in the 51-day period. However, the survival of fish at the
other concentrations did not differ significantly from the controls
after 51 days and 45 weeks of exposure.
JY Mauck, B., Annual Progress Report: 1972 (unpublished data), Fish-
Pesticide Research Unit, Bureau of Sport Fisheries and Wildlife,
La Crosse, Wisconsin (1972).
91
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Table 14. TOXICITY OF CAPTAN: 96-HR TL50 AND LTC
FOR THREE SPECIES OF FISH£/
Species
Mean temperature
(and range)
96-Hr TL
(US/1)
Fathead minnow
25.0
(25.1-25.4)
65
(59-72)
64
(58-70)
Bluegill
25.0
(24.8-25.0)
72
(47-111)
72
(47-111)
Brook trout
11.7
(11.5-12.0)
34
(22-52)
29
(18-46)
a/ Hermanutz et al., op. cit. (1973).
b_/ 957o confidence limits in parentheses.
_c/ Lethal threshold concentration.
Reproduced by persmission of Information Canada.
92
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Table 15. TOXICITY OF CAPTAN TO FISH IN STANDARD RECONSTITUTED
STATIC WATER AT 12°C
Average ^^50 Values (ug/X) and
weight 957o confidence limits
Formulation
Captan
(90-98%)
Captan
(90-98%)
Captan
(90-98%)
Captan
(90-98%)
Captan
(90-98%)
Captan
(90-98%)
(g) Species 24 hr
0.81 Coho salmon 138
118-160
0.70 Chinook salmon 139
115-168
0.73 Brown trout 81.0
69.8-94.0
0.42 Lake trout 53.0
44.5-63.1
0.34 Fathead minnow 290
211-398
0.67 Yellow perch 540
420-695
96 hr
137
117-160
120
103-140
80.0
63.8-100
49.0
40.1-59.9
200
168-238
420
311-520
Data from Mauck, op. cit. (1972).
93
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Table 16. TOXICITY OF CAPTAN TO FISH IN CITY FILTERED WATER AT
12°C (FLOW-THROUGH SYSTEM)
Formulation
Captan
(90-98%)
Captan
(90-98%)
Captan
(90-987,)
Captan
(90-98%)
Captan
(90-98%)
Average
weight
(g) Species
0.75 Coho salmon
0.60 Brown trout
0.42 Lake trout
0.43 Fathead minnow
1 . 1 Yellow perch
LCcjQ Values
; (ug/4) and
957, confidence limits
24 hr
75.0
65.0-86.6
26.2
21.9-31.3
75.0
51.7-109
152
124-186
> 154
96 hr
56.5
52.3-61.0
26.2
21.9-31.3
51.0
39.3-66.2
134
101-178
123
98.8-153
Data from Mauck, op. cit. (1972).
94
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Table 17. SURVIVAL AND GROWTH OF FATHEAD MINNOWS DURING
CHRONIC EXPOSURE TESTS
Measured captan concentration (ug/£)
63.5 39.5
Item *&L 1 A B
Survival (%) 4 b/ 0 80 72
Total length (mm)
Mean - - 21.3 b/ 20.2
vo Range - - 28-16 30-13
oi
Survival (%) 0 b/ o 73.3 80.0
Males/females at
termination - - 5/6 6/7
Mean total length (mm)
Male - - 57.4 b/ 63.7
Female - - 50.0 b/ 51.4
Mean weight (g)
Male - - 2.4 3.2
Female - - 1.3 1.4
16.8 7
A B A
51 Days
84 88 92
21.6 22.0 21.6
29-14 32-13 34-13
45 Weeks
100 92.3 100
6/5 5/7 6/4
64.5 67.4 69.2
50.6 54.9 55.5
3.2 3.7 4.0
1.3 1.5 1.6
.4
B
84
22.0
28-13
100
5/6
65.2
57.0
3.2
1.7
3.3 0
A .B A
76 72 88
23.4 22.1 23.
33-19 31-14 33-
100 90.9 100
6/5 3/7 5/8
61.2 63.3 64.
59.2 54.4 58.
2.5 3.1 2.
1.7 1.4 1.
(controlj
_B
80
0 22.4
10 30-12
90.9
4/6
2 69.3
1 58.5
8 3.8
7 1.8
a./ A and B indicate duplicate test chambers.
ID/ Values are significantly different from controls (P = 0.05).
Reproduced by permission of Information Canada.
Source: Hermanutz et al., op. cit. (1973).
-------
Although statistical significance could not be shown, the investigators
reported that mean spawnings per female and mean eggs spawned per female
appeared to be adversely affected at 39.5 and 16.8 fig/liter. Growth and
survival of the F]_ generation were reduced in 39.5 ug/liter after 30
days but no significant differences in growth or survival of the ~F^
generation were observed between treatments at 16.8, 7.4, and 3.3 jug/
liter and the untreated controls.
The scientific names of the fish studied in this review are listed
in Table 18.
Feeble swimming at the surface was reported by Hermanutz et al.
(1973) to be a characteristic response in fathead minnows, to exposure
to cap tan.
There is no known data on the effects (if any) of captan to fishes
under field conditions, although registered labels of captan-containing
commercial pesticides carry the caution statement "This product is toxic
to fish. Keep out of lakes, streams or ponds." (Captan is not registered
for use directly on bodies of water.)
Lower Aquatic Organisms
Laboratory studies - Frear and Boyd (1967)-=.' observed a LC5Q (26 hr)
of 1.3 ppm for Daphnia magna in a static water system.
Paris and Lewis (1973).?_/ conducted a comprehensive literature search
on the role of aquatic microbial metabolism in the environmental degradation
of 10 selected pesticides, including captan. There is little available
information in this area to date. The U.S. Environmental Protection Agency's
Athens, Georgia, Laboratory, has initiated experimental work on the inter-
actions between captan and aquatic organisms. Various studies on captan
began at the end of 1973. In preliminary experiments with captan, the concen-
tration of the fungicide decreased rapidly in bacterial cultures to which it
was added. Only traces of the 3.0 ppm initial concentration were still detec-
table after 19 hr. The concentration of captan decreased more rapidly in the
inoculated than in uninoculated preparations.
I/ Frear, D. E. H., and J. Boyd, "Use of Daphnia magna for microbioassay
of Pesticides," J. Econ. Entomol., 60:1228-1236 (1967).
2J Paris, D. F. , and D. L. Lewis, "Chemical and Microbial Degradation of
10 Selected Pesticides in Aquatic Systems," Residue Rev., 45:95-124
(1973).
96
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Table 18. SPECIES OF FISH USED
IN TOXICITY TESTS WITH CAFTAN
Common name
Bluegills
Brook trout
Brown trout
Carp
Channel catfish
Chinook salmon
Coho salmon
Cutthroat trout
Fathead minnow
Goldfish
Lake trout
Rainbow trout
Yellow perch
Zebrafish
Scientific name
Lepomis macrochirus
Salvelinus fontinalis
Salmo trutta
Cyprinus carpio
Ictalurus punctatus
Oncorhynchus tshawytscha
Oncorhynchus kisutch
Salmo clarki
Pimephales promelas
Carassius auratus (Cyprinus
auratus)
Salvelinus namaycush
Salmo gairdneri
Perca flavescens
Brachydanio rerio
97
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Lazaroff (1967)i/ studied the effects of pesticides on freshwater
algae in order to evaluate the use of such organisms in biological assays
for pesticide pollution. In enrichment cultures, algal development was
initially inhibited by captan at 1.0 ppm. Eventually, algal growth de-
veloped in such preparations due to the selections of resistant forms.
Field studies - Brisou and Denis (1969)-?/ also used a bacteriological
method to monitor pesticides in seawater, shore mud, and shellfish
including oysters, clams, cockles and mussels. In their method, the
shellfish are removed from their shells and pulverized mechanically.
Pesticide residues were extracted by suitable solvents and the use of
appropriate extraction and centrifugation equipment and procedures.
Bands of heavy blotting paper are impregnated with the final extracts,
dried, and then placed on a nutrient medium in a petri dish with strains
of Bacillus licheniformis and F1avobacterium sp. These cultures are
then incubated for 20 to 24 hr at 37°C. A zone of growth inhibition
around the paper bands characterizes a positive result. In this procedure,
captan demonstrated "very great inhibitory activity" for both test
organisms. The authors state that the method is specific for captan
and carbamates.
No additional reports on the interactions between captan and lower
aquatic organisms were found. The data reviewed in this area is not
sufficient for making an evaluation of captan's effects on aquatic
microorganisms. No data were obtained on possible effects of captan
on phytoplankton or most other aquatic plants, zooplankton, or benthic
invertebrates. The summary of data on the toxicity of pesticides to
aquatic animals in the Federal Water Pollution Control Administration's
Publication on "Water Quality Criteria" does not include any data on
captan. The review of the ecological effects of pesticides on non-
target species by Pimentel (1971)1.' likewise does not contain any
information on the effects of captan on aquatic organisms.
I/ Lazaroff, N., "Algal Response to Pesticide Pollutants," Bacteriol
Proc., 48 (1967). '
21 Brisou, J., and F. Denis, "The Use of Bacteria for the Detection of
Certain Pesticides," Compt. Rend. Soc. Biol.. 163(6):1426-1427
I/ Pimentel, D., "Ecological Effects of Pesticides on Nontarget Species "
Executive Office of the President, Office of Science and Technology,
Superintendent of Documents, U.S. Government Printing Office
Washington, D.C. (1971). '
98
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Effects on Wildlife
Laboratory Studies - Heath et al. (1972)I/ have calculated LC50 values
(ppm in feed) for four species of birds. The values were determined by
administering captan to mallards, pheasants, bobwhite quail and Japanese
quail for 5 days; test animals were 2 weeks of age. The data from these
determinations are summarized as follows:
Specie
Bobwhite quail
Japanese quail
Pheasant
Mallard duck
Number of
concentrations
tested
6
3
3
3
Birds per
concentration
8
14
12
10
C^Q (ppm in
feed)
> 2,400
> 5,000
> 5,000
> 5,000
Schafer (1972)—' found captan not to be toxic to the red-winged
blackbird (Agelaius phoeniceus) or the starling (Sturmus vulgaris) at
a single oral dose of 100 mg/kg.
Based on these limited data, the toxicity of captan to birds does
not appear to be of a high order by dietary routes. Dermal toxicity,
inhalation toxicity, etc., have not been reported.
No reports were found on toxicity of captan to wild mammals as
determined by controlled studies.
FieJLd Studies - Data on the effects (if any) of captan to wildlife under
field conditions appear to be nonexistent.
Data from laboratory investigations on the toxicity of captan to
birds indicate that captan is relatively nontoxic to these species. As
far as could be determined, no adverse effects on wildlife have been
attributed to captan in more than 20 years of commercial use in the U.S.
and in many other countries.
I/ Heath, R. G., J. W. Spann, E. F. Hill, J. F. Kreitzer, "Comparative
Dietary Toxicities of Pesticides to Birds," U.S. Bureau of Sport
Fisheries and Wildlife, Special Scientific Report, Wildlife No. 152,
pp. 1-40 (1972).
2J Schafer, E. W., "The Acute Oral Toxicity of 369 Pesticidal Pharmaceutical,
and Other Chemicals to Wild Birds," Toxicology and Applied Pharmacology,
21, 315-330, (1972).
99
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Effects on Beneficial Insects
Bees - Beran and Neururer (1955)i/ investigated the toxicity to bees of
a large number of pesticides, including captan. The LD5Q of captan,
when fed orally, was 2.44 ug/bee, placing it among those pesticides
considered to be relatively nontoxic to the honeybee.
Anderson et al. (1957)— I found no significant mortality associated
with bees sprayed with captan at two pounds/100 gal.
Parasites and Predators - Bartlett (1963)—' reported that when captan
was sprayed in orchards at the rate of 1 lb/100 gal. of water some
mortality of parasitic wasps (especially Metaphycus helvqlus) occurred.
There was little or no mortality of predatory coccinellid beetles.
Croft and Nelson (1972)— studied the toxicity of more than 20
commonly used pesticides including captan to several populations of the
beneficial predatory mite Amblyseius fallacis. Predators were collected
in August and September from several commercial Michigan apple orchards,
and laboratory colonies started. Toxicity was determined by exposing
mites to slides, and, in another test series, to apple leaf disks immersed
in field use concentrations of the test pesticides. By both methods,
captan had little activity on several strains of A. fallacis.
I/ Beran, F., and J. Neururer, "The Action of Plant Protectants on the
Honey Bee (Apis mellifera). I. Toxicity of Plant Protectants to
Bees," Pflanzenschutz Ber., 15:97-147 (1955).
2J Anderson, E. J., F. R. Shaw, and D. J. Sutherland, "The Effects of
Certain Fungicides on Honey Bees," Jour. Econ. Ento., 50(6), 570-573,
(1957). ~
3/ Bartlett, B. R., "The Contact Toxicity of Some Pesticide Residues
to Hymenopterous Parasites and Coccinellid Predators," J. Econ.
Entomol., 56:694-698 (1963).
47 Croft, B. A., and E. E. Nelson, "Toxicity of Apple Orchard Pesticides
to Michigan Populations of Amblyseius fallacis," Environ. Entomol.,
l(5):476-579 (October 1972). ——
100
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Nelson et al. (1973)1' studied the toxicity of pesticides includ-
ing captan to another important predatory mite Agistemus fleschneri.
Field collected specimens were exposed to the test pesticides in the
laboratory by the slide-dip method. Slides treated with captan at the
rate of 2 Ib AI/100 gal. of a 50% wettable powder formulation produced
the lowest percent mortality (1.3% at 48 hr) among 35 pesticides
studied. In field tests, five applications of captan 50% wettable
powder (three at 20 ounces, two at 10 ounces/100 gal.) were not toxic
to the predatory mite, nor to the phytophagous mite Panonychus ulmi.
In mixtures with insecticides, the presence of captan in the combina-
tion did not result in higher predator mortality. The authors char-
acterize captan as "rather innocuous" to A. fleschneri.
Several Canadian and European workers report generally similar ob-
servations. MacPhee and Sanford (1956.2/ and 197ll/) studied the in-
fluence of spray programs on the fauna of apple orchards, specifically
beneficial arthropods. Captan was found to be "relatively harmless."
There was little or no reduction in the number of beneficial predacious
and parasitic arthropods when captan was used in orchards at recommended
rates.
Benoit and Parent (1973)-!' studied the population densities of the
European red mite (Panonychus ulmi), on apples in Quebec during the
period 1960 through 1967. Abiotic factors responsible for the natural
reduction of P. ulmi were predacious mites, arachnids, coccinellids,
pentatomids, thrips and mirids. The experimental plot where these
studies were conducted was sprayed regularly with fungicides, primarily
captan, for the control of diseases. The captan sprays did not appear
to adversely affect any of the natural enemies of the European red mite.
I/ Nelson, E. E., B. A. Croft, A. J. Howitt, and A. L. Jones, "Toxicity
of Apple Orchard Pesticides to Agistemus fleschneri," Environ.
Entomol., 2(2):219-222 (1973).
_2/ MacPhee, A. W., and K. H. Sanford, "Influence of Spray Programs on
the Fauna of Apple Orchards in Nova Scotia. X. Effects of Some
Beneficial Arthropods," Can. Entomol., 88:631-634 (1956).
_3/ MacPhee, A. W., and K. H. Sanford, "The Influence of Spray Programs
on the Fauna of Apple Orchards in Nova Scotia. XII. Second Sup-
plement to VII. Effect on Beneficial Arthropods," Can. Entomol.,
93:671-673 (1961). In: Pimentel (1971).
47 Benoit, J. P. H., and B. Parent, "Natural Population Densities of
the European Red Mite on Apple in Quebec," Environ. Entomol.,
2(6)-.1064-1068 (1973).
101
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Schneider (1958)1/ found that captan at normal rates of applica-
tion in orchards had no effect on the parasitic wasp, Aphelinus mall.
Van deVrie (1967),-/ however, found that when captan was applied to
apple trees at the rate of 0.15%, some mortality to Aphelinus mail, and
also to the predatory bug Orius sp. resulted. In the same study, Van
deVrie found this rate of captan to be harmless to the predatory bug,
Anthocoris nemorum.
Besemer (1964)!/ found that captan applied to fruit trees at
normal recommended dosages did not harm the beneficial predatory mite,
Thyplodromus sp., or such beneficial parasitic wasps as Mormoniella sp.
and Aphelinus mali.
Ankersmit et al. (1962)^/ reported that in laboratory tests, a
spray concentration of captan of 0.125% caused no mortality to the para-
sitic, wasp, Mormoniella vitripennis_.
In tests of potted apple trees, captan at the rate of 0.2%, caused
little or no toxicity to beneficial predatory mites (Van deVrie, 19622.')
Ulrich (1968).§/ found that captan residues remaining on a surface
after treatment at the rate of 1,000 ppm had little or no effects on
female adults of the parasitic wasp Trichogramma sp. when exposed for
10 hr.
!_/ Schneider, H., "Untersuchungen uber den Einfluss neuzeitlicher
Insektizide und Fungizide auf die Blutlauszehrwesp (Aphelinus mali
Hald.)," Z. Ang. Ent., 43:173-196 (1958). In: Pimentel (1971).
_2/ Van deVrie, M., "The Effect of Some Pesticides on the Predatory Bugs
Anthocoris nemorum L. and Orius Spec, and on the Wooly Aphid Para-
site Aphelinus mali Hald.," Entomophaga, Me. hors Serie 3:95-101
(1967). In: Pimentel (1971).
_3/ Besemer, A. F. H., "The Available Data on the Effect of Spray Chemi-
cals on Useful Arthropods in Orchards," Entomophaga, 9:263-269
(1964). In: Pimentel (1971)
4/ Ankersmit, G. W., J. T. Locher, H. H. W. Velthuis, and K. W. B. Zwart,
"Effect of Inse'cticides, Acaricides, and Fungicides on Mormoniella
vitripennis Walker," Entomophaga, 4:251-255 (1962). In: Pimentel
(1971).
5_/ Van deVrie, M. , "The Influence of Spray Chemicals on Predatory and
Phytophagous Mites on Apple Trees in Laboratory and Field Trials in
the Netherlands," Entomophaga, 7:243-250 (1962). In: Pimentel
(1971).
<5/ Ulrich, H. , "Versuche uber die Empfindlichkeit von Trichogramma
(Hymenoptera, Chalcidoidea)gegenuber Fungiziden," Anz. Schadli ngskunde.
51:101-106 (1968). In: Pimentel (1971;.
102
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Russian workers (Kapitan et al., 1972—') investigated the toxicity
of a number of pesticides to larvae of the aphid lion, Chrysopa carnea.
The pesticides were applied at concentrations ranging from 0.03 to 1.07=.
Captan was among those least toxic to this predator.
These observations by U.S., Canadian, West European, and Russian
workers indicate that captan at fungicidally effective rates of applica-
tion appears to be relatively harmless to beneficial predators and para-
sites occurring in deciduous fruit orchards. Among all of the accounts
reviewed above, there was only one report of "some mortality" to the
predatory bug Orius sp., and to the parasitic wasp, Aphelinus mali.
Interactions with Lower Terrestrial Organisms
Microflora - Agnihotri (1971).?/ studied the persistence of captan and
its effects on the microflora, respiration and nitrification of a forest
nursery soil. Captan was applied to the soil (fine sand with 3.87o
organic matter and a pH of 6.1) at the rates of 62.5, 125 and 250 ppm.
Ammonium sulfate (100 ppm N) was thoroughly mixed with the soil, and
calcium carbonate was added to neutralize the acidity produced in
nitrification. The soil moisture was adjusted, and the soil samples
thus prepared were incubated in the laboratory in glass pint milk
bottles. Captan affected the soil microflora and some of its activi-
ties. Captan killed the population of two pathogenic fungi, Rhizoctonia
and Pythium spp. After an initial decrease, the population of actino-
mycetes increased gradually. Some bacteria also increased, but after
35 days, the population had dropped back to that of the control soil.
All concentrations of captan tested impaired nitrification for varying
periods of time. Respiration in the soil was inhibited initially, but was
subsequently stimulated. The author suggests that this may have been
due to the use of captan decomposition products by the microorganisms.
The initial depression of carbon dioxide production was directly pro-
portional to the captan concentration in the soil.
_!/ Kapitan, A. I., G. I. Sukhoruchenko, and Y. S. Tolstova, "Toxicity
of Pesticides for Aphid Lions," Zashch. Rast., 7:24-25 (Moscow)
(1972).
2_l Agnihotri, V. P., "Persistence of Captan and Its Effects on Micro-
flora, Respiration and Nitrification of a Forest Nursery Soil,"
Can. J. Microbiol.. 17(3):377-383 (1971).
103
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Wainwright and Pugh (1973)i/ investigated the effects of captan on
the nitrification rate of soil amended with ammonium sulfate in com-
parison to soils not treated with a fungicide, but also amended with
ammonium sulfate. Under these conditions, low concentrations of captan
(5 ug Al/g of soil) stimulated nitrification activity of the soil,
while ammonification was not significantly affected. However, at (un-
specified) higher concentrations, ammonification appeared to be markedly
increased. It is noted that the rate of 5 ug of captan per gram of
soil which stimulated nitrifiction in these tests is more than 10 times
lower than the lowest rate studied by Agnihotri (1971).
Chinn (1973)—' studied the effects of captan (and several other
fungicides) on microbial activities in the soil by a bioassay method.
Included in these tests were three species of bacteria, two of actino-
mycetes, and three of fungi. Captan (and two other fungicides) showed
little or no activity under these conditions. Concentrations studied
ranged from 1.0 to 1,000 ppm. The author points out that the captan
results may have been influenced by its low solubility.
Tews (1971)—' investigated the effects of captan and a number of
other fungicides on the microfungi of a cattail marsh. Captan at "field
concentration" was applied to cultures of the predominant microfungi of
the marsh, i.e., Hansenula saturnus, Mucor hiemalis, Penicillium stipitatum,
and Trichoderma viride. The growth of all four fungi was inhibited by
captan. However, when captan was subsequently applied to field plots in
a cattail marsh, it did not reduce the number of microfungal propagules
in the litter, water or mud, while several other chemicals studied did
produce such effects. This study was unreplicated and preliminary in nature.
Hansen (1972)-' studied the effects of captan and other fungicides
on 211 strains of bacteria isolated from various soils, from marine and
_!_/ Wainwright, M. , and G. J. F. Pugh, Soil Biol. Biochem., 5 (5): 577-584
(1973).
2/ Chinn, S. H. F., "Effect of Eight Fungicides on Microbial Activities
in Soil as Measured by a Bioassay Method," Can. J. Microbiol., 19(7):
Ill-Ill (1973).
_3/ Tews, L. L., "Effects of Selected Fungicides and Soil Fumigants Upon
the Microfungi of a Cattail Marsh," Proc. Conf. Great Lakes Res.
(14th), pp. 128-136 (1971).
4/ Hansen, J. C., "The Effect of Some Sulphur and Mercury Containing
Fungicides on Bacteria," Chemosphere, 1(4):159-162 (1972).
104
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freshwater sediments, and from outdoor dust. Several of the chemicals
tested produced a marked inhibitory effect, and there were considerable
differences between chemicals and test organisms. The author concluded
that captan appears to pose no risk to a bacterial population since most
strains were "resistant or relatively resistant" to it.
Naumann (1970)—' studied the effects of captan and several other
fungicides on the soil microflora. In field and greenhouse trials, cap-
tan at the concentration of 250 ppm stimulated the soil bacteria in loam
soil for about 12 weeks. Actinomycetes were least affected. Most of
the physiological groups of the soil bacteria such as nitrogen-fixing
organisms, cellulose decomposers, spore-forming bacteria, and denitrify-
ing bacteria were stimulated. In some instances, the addition of captan
resulted in a decrease in the nitrifying bacteria, ammonifying forms,
anaerobic bacteria, and soil algae. Azotobacter chroococcum was signifi-
cantly inhibited for several weeks. Many soil fungi including Penicillium,
Aspergillus, Trichoderma, Cephalosporium, Hyalopus, Acrostalagmus,
Verticillium, Aleurisma, Sporotrichum, Strachybotrys, Phymatotrichum,
Phoma, Spicaria, Hormodendrum, Claddsporium, Scopulariopsis, Oospora and
Fusarium were reduced markedly by the application of captan. After a
short inhibition, the soil respiration was stimulated by 250 ppm of cap-
tan, while the dehydrogenase activity was strongly reduced for 4 weeks.
Domsch (1959).2/ reported that the effect of captan on the soil
microflora varies with the dosage rates. Applied to soil at the "low"
rate of 400 to 600 ppm, captan reduced the populations of sensitive
algae, actinomycetes and fungi, while bacterial numbers remained unchanged.
Picci (1956)^.' found that at the rate of 1,000 ppm, captan inhibited
nitrifying bacteria, but affected ammonifying bacteria only slightly. Both
Picci (1956) and Domsch (1959) observed that little permanent damage occurs
to fungi such as Penicillium, Pythium, Fusarium, and Rhizoctonia in soils
treated with captan. Lukens (1968)^t/ found Trichoderma to be quite
_!/ Naumann, K., Jr., "The Dynamics of Soil Microflora After the Use of
the Fungicides Olpisan (Trichlorodinitrobenzene), Captan and
Thiuram," Arch. Pflanzenschutz, 6(5):383-398 (1970).
2/ Domsch, K. H., "The Effects of Soil Fungicides. III. Quantitative
Changes in Soil Flora," Z. Pflanzenkrankh, Pflanzenschutz, 66:17-26
(1959) .
3/ Picci, G., "Effect of Captan on Soil Microorganisms," Agr. Ital. (Pisa)
56:376-382 (1956). In: Torgeson (1969).
4/ Lukens, R. J., (1968), unpublished data, quoted from Torgeson, D.C.
(1969).
105
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resistant to captan also. Torgeson (1969)!/ states that "soil bacteria
are resistant to captan."
Kokke (1970)-/ studied the soil and water microflora in search of
DDT-accumulating, resistant, sensitive, and degrading microorganisms.
Microbial cultures were isolated from tap water, polluted surface v,ater,
garden soil, and recently pesticide treated nursery soil. The author
reports that DDT-accumulating bacteria were more plentiful in the media
on which captan had been sprayed.
Langkramer (1970)!/ applied a "rapid and simple" laboratory method
for testing the effects of captan and other pesticides on soil biota.
This German paper, available to us only in abstract form, includes a
fairly detailed description of the method, but no results.
Tiefenbrunner (1973)^ reported that captan decreased the formation
of aerobic mycelia in cultures of Suillus plorans when added to culture
media at 0.05, 0.1, and 0.37=.
Several authors investigated the effects of captan on beneficial
soil microorganisms, particularly the nitrogen-fixing bacteria of
leguminous plants.
Gillberg (1971)!/ studied the effects of captan on two strains each
of Rhizobium melilotj-, R. l_eguminosarum, and R. trifolii. These
I/ Torgeson, D. C. (ed.), "Fungicides, an Advanced Treatise," Vol. II.
"Chemistry and Physiology," Chapter V., "Captan and the R-SCCls
Compounds," Academic Press (1969).
2/ Kokke, R. , "DDT: Its Action and Degradation in Bacterial Popula-
tions," Nature, 226(5249):977-978 (1970).
3/ Langkramer, 0,, Jr., "Investigations Into the Influence of Pesticides
on Soil Microorganisms in Pure Cultures by Means of a Laboratory
Method," Zentr. Bakteriol. Parasitenk., Abt. II.: Na; 125(7):713-
722 (1970).
4/ Tiefenbrunner, F., "Mycelial Weight Increase of Myconnhizal Fungi
Under the Influence of Fungicides in vitro," Z. Pilzk, 38(1-4):
105-107 (1973).
_5_/ Gillberg, B. 0., "On the Effects of Some Pesticides on Rhi zobi urn and
Isolation of Pesticide-Resistant Mutants," Arch. Mikrobiol., 75(3):
203-208 (1971).
106
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organisms were plated on a glucose medium containing various concentra-
tions of captan. Resistant mutants were selected by culturing techniques
and ultraviolet irradiation was used to induce mutations when no spontaneous
mutants were found. All wild strains were inhibited by captan at 50 ug/
ml. Spontaneous mutants resistant to this captan concentration were
isolated from all but one of the strains. The ability to infect legumi-
nous plants was not affected in any of the resistant mutants that were
isolated.
Petrovic (1970)i/ studied the effect of several pesticides on the
nodulation of alfalfa and red clover. Captan (concentration not given)
was more toxic to the nodulation of alfalfa than of red clover, while
the reverse was true for another fungicide studied under the same con-
ditions .
Mukewar and Bhide (1969)^7 and Muthusamy (1973)!/ studied the ef-
fects of captan on the nodulation of peanuts (groundnuts) by Rhizobium
species. Mukewar and Bhide found no significant effects on nodule num-
bers or plant weight with peanut seeds grown on steamed soil treated
with captan (rate not given). When peanuts were grown on unsterilized soil
fungicide treatment increased both the nodule number and plant weight.
When Rhizobium inoculated plants were grown in sterilized soil,
sterilized sand, or unsterilized soil from captan treated seeds, higher
plant weight and nodule numbers were observed in comparison to uninocu-
lated controls not treated with the fungicide. The authors conclude
that treatment of peanut seeds with captan as a seed protectant will not
adversely affected bacterial inoculants. By contrast, Muthusamy (1973)
reported that seed treatment of peanuts with captan at the rate of 2 g/kg
of seed inhibited Rhizobium growth. The reasons for these divergent ob-
servations are not clear from the available data.
I/ Petrovic, V., "Effect of Some Pesticides on Nodulation of Medicago
sativa (Alfalfa) and Trifolium pratense (Red Clover)," Mikrobiologija,
7(2):183-193 (1970).
2/ Mukewar, P. M., and V. Bhide, "Effect of Seed Treatment with Fungi-
cides and Antibiotic Aureofungin on Nodulation by Rhizobium in
Groundnut," Hindustan Antibiot. Bull., 12(2-3):75-80 (1969).
3/ Muthusamy, S., "Effect of Seed Dressing and Soil Fungicides on the
Growth of Rhizobium in Groundnut," Pesticides, 7(l):27-28 (1973).
107
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Fiscor and Nil Lo Piccolo (1970)!/ studied the effects of tempera-
ture on the mutagenicity of captan to several strains of E. coli and S.
typhimurium using captan in the form of "tomato vegetable dust" (con-
centration not given in abstract). A 1:10 suspension of the pesticide
in sterile distilled water was prepared, and aliquots were allowed to
stand at room temperature, steamed-sterilized for 15 min at about 100°C,
and autoclaved for 15 min at 15 Ib pressure at about 121°C, respectively.
After cooling, these captan-containing suspensions were placed on plate
cultures of the test organisms. Mutagenic response was determined by
counting the number of revertant colonies appearing on the plates in
96 hr at 37°C. All captan treatments significantly increased reversions
compared to the controls. The steam-sterilized pesticide induced five
times fewer reversions, the autoclaved material 21 times fewer rever-
sions than the room temperature check.
Microfauna - Drift (1970)!/ reviewed the interrelationships between a
number of pesticides and the soil fauna. Captan had only a temporary
effect on the microfauna including millipedes, dipterous larvae, col-
lembola, oribatid mites, earthworms, enchytraeids, nematodes, insect
larvae, centipedes, mesostigmatic mites, carabids and spiders. Soils
studied included samples of arable land, horticultural soils, grass-
land, orchards, and woodlands.
Martin and Wiggans (1959)!/ studied the toxicity of captan to earth-
worms, Eisenia joetida, in the laboratory. When earthworms were immersed
for 2 hr in suspensions of captan at 10 ppm, there was little mortality,
but at 100 ppm all of the earthworms were killed.
DeVries (1962)—' investigated the toxicity of moderate and very high
rates of captan to two species of earthworms. Soil treated with captan
at 15, 60 and 500 Ib/acre was nontoxic to Lumbricus species after 32 days
_!/ Fiscor, G., and G. M. Nii Lo Piccolo, "The Effect of Temperature on
the Mutagenicity of Captan," Newslett. Environ. Mutagen Soc., 3:38
(1970).
2/ Drift, J., "Pesticides and Soil Fauna," Meded. Rijksfac.
Landbouwwetensch Gent, 35(2):707-716 (1970).
_3/ Martin, W. L. , and S. C. Wiggans, "The Tolerance of Earthworms to
Certain Insecticides, Herbicides, and Fertilizers," Oklahoma Agr.
Exp. Stat. Proc. Ser. P-334 (1959). In: Pimentel (1971).
4/ DeVries, M. L. , "Effect of Biocides on Biological and Chemical
Factors of Soil Fertility," Ph.D. Dissertation, University of
Wisconsin, Madison, Wisconsin, 89 pages (1962). In: Pimentel
(1971).
108
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exposure. Helodrleus species was unaffected at the two lower rates, but
there was 47% mortality after 32 days exposure to the 500 Ib/acre rate.
The data reviewed in this subsection indicate that captan affects
a number of soil bacteria and fungi under laboratory conditions. Under
field conditions, effects from normal concentrations (i.e., those result-
ing from application at recommended rates) of captan appear to be either
nonexistent or very short-lived. In addition to its principal use as a
foliar fungicide, captan is recommended as a seed protectant, as a dip
for the control of rots and damping off of cuttings and bulbs, as a
potato seed piece treatment for the control of rots, and for the con-
trol of some diseases on turf and lawns. Some recommendations on some
labels also provide for broadcast application directly into the soil,
but these uses are very minor. Thus, the use of captan in accordance
with the registered labels will generally not result in high captan con-
centrations in the soil.
Few reports were found on the toxicity of captan to the lower ter-
restrial fauna. Hewever, the review by Drift (1970) and the reports
on earthworms indicate that captan is relatively nontoxic to such
organisms.
Residues in Soil
Laboratory and Field Studies - Munnecke (1958)i/ studied the soil per-
sistence of captan and three other nonvolatile diffusible fungicides in
a soil mix containing by volume 50% fine sand and 5070 Germam peat moss.
Twenty milliliters of a suspension containing 1,000 ppm of captan active
ingredient (AI) were added to flasks containing 30 g of this soil mix-
ture, plus a full complement of fertilizers. Prior to addition of the
fungicide, the flasks were treated in three different ways: one lot was
sterilized for 1 hr at 10 to 12 Ib psi steam pressure; one lot was
sterilized with gaseous propylene oxide; and one lot was left untreated.
When soil samples were plated, no growth occurred from soil treated with
steam or propylene oxide, whereas about 1 million fungal colonies and
2 to 3 million bacterial colonies were produced per gram of untreated
soil. The fungicides were added after these steps. The fungicidal
activity in the soils was determined at intervals for up to 150 days by
a bioassay technique using agar plates seeded with spores of Myrothecium
verrucaria. Under these conditions, the activity of captan persisted
for at least 65 days. There were no significant differences between
untreated, steamed, or propylene oxide-treated soil.
_!/ Munnecke, D. E., "The Persistence of Nonvolatile Diffusible Fungi-
cides in Soil," Phytopathology. 48:581-585 (1958).
109
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Burchfield (1959)i/ investigated the stability of captan and three
other fungicides in a silt loam soil with a natural pll of 4.5 to 5.
This soil was composted with manure and fertilizer, and with sufficient
limestone to increase the pH to above 6, then stored in the field for
2 to 3 years. Captan was mixed at rates of 10 and 100 ug of active in-
gredient per gram of soil with moist and air dried soil. The moist
soil had a pR of 6.4 and contained 17.5% water; the air dried soil had
a pH of 6.2 and contained 1.6% water. Captan residues remaining in the
soil samples were analyzed colometrically. The half-life of captan in
the dry soil was more than 50 days; in the moist soil, 3.5 days; and
in a phosphate buffer (pH 7), 0.1 day,
Kluge (1969)-/ studied the effects of soil pH on the degradation
and residual effectiveness of captan and two other fungicides in the
soil. The rate of degradation of captan was not affected by hydrogen
ion concentrations ranging from pH 3.6 to 7.4, while the other two
fungicides, TMTD and ferbam, were markedly affected by differences in
pH. Captan was applied to the soil in the form of a 507o formulation,
at the rate of 200 ppm of active ingredient. Its biological effective-
ness declined to less than 107o within 10 weeks after initiation of the
test, as determined by a bioassay technique measuring growth inhibition
of a test fungus, Rhizoctoni a solani, on agar plates.
Griffith and Matthews (1969).£/investigated the persistence of cap-
tan well incorporated into the soil, and added to the soil on the sur-
face of glass beads (simulating seeds). In the first test series,
captan at 125 ppm was thoroughly mixed into unsterilized medium loam
soil having a moisture content of 457», In the second series, the fungi-
cide was added to the soil on the surface of 0.7 mm diameter glass beads
at a rate equivalent to 125 ppm. The amount of captan remaining in the
soil was measured by bioassay after 0, 1, 2, 4, 8, and 21 days. Plugs
of soil containing captan were incubated on agar plates seeded with
spores of Myrothecium verrucaria, and the diameter of the zone of fungal
_!/ Burchfield, H. P., "Comparative Stabilities of Dyrene, l-Fluoro-2,4-
dinitrobenzene, Dichlone and Captan in a Silt Loam Soil," Contrib.
Boyce Thompson I_ns_t_^, 20:205-215 (1959).
2/ Kluge, E., "Der Einfluss der Bondenreaktion auf den Abbau and die
Wirkungsdauer von Thiuram, Ferbam, und Captan in Boden," Arch.
Pflanzenschutz, 5(4):263-271 (1969).
3/ Griffith, R, L., and S. Matthews, "The Persistence in Soil of the
Fungicidal Seed Dressing Captan and Thiuram," Ann. Appl. Biol. ,
64(1):113-118 (1969).
110
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inhibition was measured. The diameters of the inhibition zones were then
converted into parts per million of fungicide by means of regression
equations for the calibrations. When mixed with the soil, captan showed
very low persistence, having a half-life of 1 to 2 days. By contrast, when
added to the soil on the surface of glass beads, captan persisted; there
was little change in the initial concentration after 21 days. The authors
concluded that captan persists far longer in the soil when localized in
high concentrations than when uniformly distributed. The results help to
explain the effectiveness of captan as a seed protectant, despite its
apparently low persistence in the soil.
Foschi et al. (1970)— / studied the degradation and vertical movement
of captan and several other pesticides in soils. In their tests, DDT,
dieldrin, captan and benlate had about the same degree of persistence;
another group of pesticides was less persistent.
Suzuki and Nose (1970)— / studied the decomposition of pentachloro-
phenol (PGP) in farm soil. At low concentrations (100 ppm) , the rate of
PGP decomposition varied with soils, but at high concentrations (1,000 ppm)
there were few differences in the rate of PCP decomposition between different
soil types at 20 and 28°C. The rate of PCP decomposition was suppressed
slightly when captan was added to the system.
Pack (1974)1/ studied the fate of 5.33 ppm of 14C carbonyl- labeled
captan in a sandy loam soil. Degradation was rapid; after 7 days 99% of
the captan had been degraded. Other than 14C02, the two major metabolites
were tetrahydropthalimide, which reached a maximum level of 66% of applied
14C in 7 days, and tetrahydropthalimic acid which reached a maximum level
of 16.5 per cent in 14 days. Several other minor products were observed,
but all reached a maximum level within 37 days. 14C02 evolution was measured
throughout the experiment; after 322 days 95% of the applied radioactivity
could be accounted for as
Monitoring Studies - Stevens et al. (1970)A/ reported on a pilot monitoring
study conducted nationwide at 51 locations in 1965, 1966, and 1967 to
!_/ Foschi, S., Jr., A. Cesari, Jr., I. Ponti, Jr., P. G. Bentivogli, Jr.,
and A. Bencivelli, Jr., "Study of the Degradation and Vertical Movement
of Pesticides in Soil," Notiz. Mai. Piante, 82(3):37-49 (1970).
2/ Suzuk-, T. , Jr., and K. Nose, Jr., "Decomposition of Pentachlorophenol
in Farm Soil. I. Some Factors Relating to PCP Decomposition,"
Noyaku Seisan Gijutsu, 22:27-30 (1970).
3_/ Pack, D. E., "The Soil Metabolism of Carbonyl l^C-Captan," Chevron Chemical
Co., San Francisco, Calif., File No. 773.21 (October 23, 1974).
4/ Stevens, L. J., C. W. Collier, and D. W. Woodham, "Monitoring Pesticides
in Soils from Areas of Regular, Limited, and No Pesticide Use," Pest.
Monit. J., 43(3)=145-163 (1970).
Ill
-------
determine pesticide residue levels in soil. Samples were collected from
17 areas in which pesticides were used regularly. 16 areas with a record
of at least one pesticide application, and 18 areas with no history of
pesticide use. Pesticide use records indicating that captan had been
used at a number of the sites samples, including Bade County, Florida;
Adams County, Pennsylvania; Quincy-Moses Lake, Washington; and Tulelake,
California; and in other fruit growing areas. However, no detections
of captan residues were reported.
In the National Soils Monitoring Program for pesticides, 1,729
samples of cropland soils from 43 states were collected in 1969 (Wiersma
et al., 1972!/). Pesticide use records indicated that captan had been
used at 11.16% of 1,684 sites sampled, at an average application rate
of 0.12 Ib Al/acre. No detections of any captan residues were reported.
In the National Soils Monitoring Program for pesticides in 1970
(Crockett et al., 197C)!/) , soil and crop samples were collected from
1,506 cropland sites in 35 states. Pesticide use records indicated
that captan was used at 106 (7.88%) of the 1,346 sites sampled, at
mean application rate of 1.68 Ib Al/acre. Crops receiving captan ap-
plications included field corn, cotton, and soybeans. Again, there
are no reports of any captan residues detected.
Carey et al. (1973)x/ monitored organochlorine pesticide residues
in soils and crops of the corn belt region in 1970. Samples of soil,
corn, cornstalks, soybeans, sorghum grain, sorghum fodder, and mixed
hay were obtained from 400 sites in 12 corn belt states. Pesticide use
records indicated that captan had been used at 68 of the 400 sites
sampled, at an average application rate of 0.03 Ib Al/acre. Captan was
the second most widely used pesticide, after atrazine. The residue
analysis method employed was capable of detecting captan. No captan
residues were detected in any of the soil, plant or seed samples analyzed.
I/ Wiersma, G. B., H. Tai, and P. F. Sand, "Pesticide Residue Levels in
Soils, FY 1969-National Soils Monitoring Program," Pest. Monit. J.,
6(3):194-201 (1972).
2J Crockett, A. B., G. B. Wiersma, H. Tai, W. G. Mitchell, and P. J.
Sand, "National Soils Monitoring Program for Pesticide Residues -
FY 1970," U.S. Environmental Protection Agency, Technical Services
Division (unpublished manuscript) (1970).
.37 Carey, A. E., G. B. Wiersma, H. Tai, and W. G. Mitchell, "Organo-
chlorine Pesticide Residues in Soils and Crops of the Corn Belt
Region, United States - 1970," Pest. Monit. J., 6(4):369-376 (1973)
112
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The data on captan soil residues reported in the foregoing four
reports from the National Soils Monitoring Program for pesticides are
subject to question because in this program, soil samples are being
shipped and stored at room temperature until processed for analysis, as
reported by Stevens et al. (1970). No information is given in these
reports on the relationships between time of pesticide application,
time of sampling, and time of processing and analysis of the samples.
No information is available on the effects of shipping and storage of
the samples on the captan residues that may have been present at the
time of sampling.
Since the results of the 1972 National Soils Monitoring Program were
not yet published at the time of this review, data from this source could
not be included.
The scientific data on the residues of captan in the soil reviewed
indicate that captan appears to be rapidly degraded in natural soil.
Captan is believed to be degradable by biological as well as by chemical
mechanisms. When captan is uniformly distributed in the soil, its half-
life is about 1 to 2 weeks at the most, only 1 to 2 days in many instances.
When applied to the soil at higher concentrations in specific areas (e.g.,
seed protectant use), captan residues persist longer in those specific
locales.
Bioaccumulation, Bipmagnification
The propensity of captan for bioaccumulation and biomagnification
was recently studies by investigators in Illinois (Illinois Natural
History Survey, 1973i')» using a laboratory terrestrial-aquatic model
ecosystem developed by Metcalf et al. (1971).A' The model ecosystem,
consisting of a terrestrial-aquatic interface and a seven-element food
chain, simulates the application of pesticides to crop plants and the
eventual contamination of the aquatic environment. The procedure and
results are described below.
I/ Illinois Natural History Survey, "The Fate of Select Pesticides in
the Equatic Environment," unpublished report prepared for the Water
Quality Office, Environmental Protection Agency, EPA Grant R-800736,
84 pages (1973).
2] Metcalf, R. L., G. K. Sangha, and I. P. Kapoor, "Model Ecosystem for
the evaluation of Pesticide Biodegradability and Ecological Magni-
fication," Jnvir^nmejitaJLS^iejic^_and_jre£hn^logY, 5(8):709-713
(1971).
113
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Sorghum (Sorghum halepense) was grown in sand to a height of 10
then treated with 5 rag of radiolabeled captan dissolved in
acetone. The design of this system and the treatment level correspond
to a farm pond surrounded by a watershed under cultivation treated with
cap tat) at 1 Ib Al/acre. After treatment of the sorghum, larvae of the
saltmarsh caterpiller (Estigmene acrea), were added to eat the treated
plant, simulating both the first member of a food chain, as well as
acting as an effective distributing agent for the labeled pesticide
inside the system. The water phase contained several members of a fresh-
water aquatic food chain, i.e., snails (Physa sp.) , water fleas (Daphnia
ma_gjaa) , and green filamentous algae (Oedogonium cardiacum) After 27
days> mosquito larvae were added to the system, and after three more
days, mosquitofish (Gambusia affinis) were added. At the end of 33
days, the entire system was taken apart, and the organisms and the
water extracted and analyzed for radioactivity. In addition, extracts
were spotted on thin-layer chromatographic plates, developed with ap-
propriate so]vents, and exposed to X-ray film to locate and identify
the chemical composition of the compounds in the solvent extract.
Metabolites were identified by co-chromatography with hypothesized
metabolites, as well as by infrared, nuclear magnetic resonance, and
mass spectrometry techniques.
At the end of the 33-day test period, none of the organisms con-
tained any captan residues. In view of the alkaline pH of the aqueous
Portion of the system, the authors suggest that captan underwent hydroly-
sis as soon as ±'r. came in contact with the water. Small amounts of
unidentifiable residues (but no captan) were detected in snails, fish,
and algae.
The authors conclude that captan does not persist in water, at"J
that "it appears that continued use of captan will not have any serious
environmental impact as it does not persist in the water of this 33-
day model ecosystem, nor does it accumulate in the fish which is the
upper member of the food chain. The probable reason for die non/per-
sistence of this fungicide in this model ecosystem is the extremely
labile trichloromethyl sulfur-nitrogen bond which can be split either
by hydrolysis or reaction with mercaptan groups in biological systems."
Environmental Transport Mechanisms
The data reviewed in the preceding subsections of thLs report sec-
tion indicate that under field conditions, captan is relatively rap-idly
degraded by chemical as well as by biological mechanisms. The degrada-
tion of captan in the soil is believed due to chemical hydrolysis and
the actions of soil microorganisms. No data was found on whether «\' not
volatilization may be an important environmental transport mechanism for
captan. The chemical has a relatively low vapor pressure.
114
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Freed et al. (unpublished data, quoted in von Rumker and Horay,
1972— ) determined the propensity of captan for volatilization and
leaching under simulated field conditions from loam soils at 25°C at
an annual rainfall of 59 in. Volatilization of pesticides under these
conditions, i.e., from a porous, sorptive medium (loam soil) in a
nonequilibrium situation, is different from volatilization from an
inert surface or from the chemical's own surface. Therefore, the en-
vironmental volatilization index assigned to pesticides studied in
this manner may or may not parallel a chemical's vapor pressure. By
this method, captan rated a volatilization index of 2, indicating an
estimated median vapor loss from treated areas of 1.3 Ib/acre/year.
This index number indicates that the propensity for volatilization of
captan from treated fields is in the intermediate range, compared to
many other pesticides.
Leaching index numbers for pesticides indicate the approximate
distance that the chemical would move through the standardized loam
soil profile under an annual rainfall of 59 in. Under these conditions,
captan rated a leaching index number of 1, indicating movement of less
than 4 in.
This data, as well as the model ecosystem studies by the Illinois
Natural History Survey (1973) reviewed in the preceding subsection,
indicates that under field conditions, residues of intact captan are
unlikely to migrate away from target areas to a significant extent.
Captan is degraded rapidly in soil and in water under environmental
conditions. Its residual effectiveness on treated plants lasts for
about 3 to 7 days. Little information is available on the nature,
toxicity, persistency, and environmental fate and effects of the
degradation products of captan.
Captan has been in large-scale commercial use in the United States
and in many other countries for about 20 years. No environmental prob-
lems have been attributed to its use as a fungicide to this date.
I/ von Rumker, R. , and F. Horay, Pesticide Manual, Vol. I, Department of
State, Agency for International Development (1972).
115
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1811-1817 (1973).
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118
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121
-------
PART II. INITIAL SCIENTIFIC REVIEW
SUBPART D. PRODUCTION AND USE
CONTENTS
Page
Registered Uses 123
Federally Registered Uses 123
State Regulations ..... 144
Production and Domestic Supply 144
Volume and Production 144
Imports • 145
Exports . 145
Domestic Supply 145
Formulations 146
Use Patterns of Captan in the United States . 148
General 148
Agricultural Uses of Captan 149
Farm Uses of Captan by Regions 153
Farm Uses of Captan by Crops 153
Home and Garden Uses of Captan 154
Captan Uses in California 154
References 172
122
-------
Registered Uses
Federally Registered Uses - Captan is a contact fungicide that is effec-
tive against a fairly broad spectrum of plant-pathogenic fungi. It is
registered and reoctnmended in the United States for use on more than 80
different crops. Tolerances for captan residues have been established on
67 raw agricultural commodities, ranging from 2 to 100 ppm. Ten of these
tolerances are currently designated as "interim tolerances." It is also
registered for use on surfaces and as a preservative for textiles, plastics,
cosmetics, etc.
The registered uses of captan by crops, established tolerances,
dosage rates, and use limitations are summarized in the "EPA Compendium
of Registered Pesticides. "jL/
The registered uses of captan are detailed in this section in a set
of two tables as follows:
Table 19: Summary of Registered Use of Captan, a listing of crops,
common and scientific names of the fungal organisms affecting each crop,
rates of application, and limitations.
Table 20: Registered uses of captan 50% wettable powder (one of
the most commonly used formulations of captan) by crops, diseases controlled
on each crop, recommended dosage rates, and general and specific directions
for, and limitations of use.
I/ U.S. Environmental Protection Agency, EPA Compendium of Registered
Pesticides, Vol. II: Fungicides and Nematicides, pp. II-C-2.1-2.11
(1973).
123
-------
Crop or Site of Application
Table 19. SUMMARY OF REGISTERED USES OF CAFTAN*
Disease or Organism Controlled ,
rb/-
Rates-5/
AI-7 Lb/100 Gal
or Lb/Acre
Limitations
I. Foliage and Fruit Applications
A. Agricultural Crops -
Fruit and Nut Crops
Almonds
Apples
Blossom Blight
(Monilinia)
Brown Rot, Twig Blight
(Monilinia)
Scab (Cladosporium)
Shothole (Coryneum)
"Bitter Rot (Glomeralla)
Black Pox (Helminthosporium)
Black Rot (Physalospora)
Botryosphaeria
(White Rot)
Botrytis Rot
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
Do not apply within
12 days of harvest
Do not feed hulls to
dairy animals or
cattle 2.0 ppm on
almonds 100.0 ppm
on almond hulls.
A C/
do~
do
do
No time limitation.
25.0 ppm
do
do
do
do
*Tabulation prepared by Eugene M. Wilson and E. N. Pelletier, Criteria and Evaluation Division, Office of Pesticides
Programs, from EPA Compendium of Registered Pesticides, Vol. II, op. cit. (1973).
a/ Rates are expressed as follows: 1) AI Lb/100 Gal or Lb/Acre for Foilage and Fruit Applications and Soil Applica-
tions; 2) AI 100 Lb Seed for Seed Applications; 3) Lb or % for Miscellaneous Agricultural Uses.
b_/ AI = Active Ingredient.
c/ do = ditto as above
-------
Crop or Site of Application
Table 19. (Continued)
Disease or Organism Controlled
Rates
AI Lb/100 Gal
or Lb/Acre
Limitations
Apples (Cont'd.)
Apricots
Brooks Spot
(Mycosphaerella)
Bullseye Rot
(Neofabraea)
Cedar-Apple Rust
(Gynosporangium)
Flyspeck
(Microthyriella)
Frogeye Leaf Spot
(Physalospora)
Quince Rust
(Gymnosporangium)
Scab (Venturia)
Sooty Blotch
(Gloeodes)
Storage Rots
Brown Rot, twig blight
(Monilinia)
Green Rot, Jacket rot
Molds
0.25-1.0
1.0
1.0
0.25-1.0
1.0
1.0
0.75-1.0
1.0-1.2
1.0
1.0
1.0-1.2
do
do
do
do
do
do
do
Apply as a post-
harvest dip or
spray. Limits:
0.12% solution.
25.0 ppm
No time limit.
50.0 ppm.
do
Post-harvest spray
or dip. 50 ppm
Storage Rots
do
do
-------
Jrop or Site of Application
Avocados
Blackberry
Blueberries
Cherries
Citrus (All)
Cranberries
Table 19. (Continued)
Disease or Organism Controlled
Blotch, Cercospora Spot
Anthracnose
(Elsinae)
Fruit Rot
Botrytis Blight,
(Graymold)
Mummy Berry
(Monilinia)
Brown Rot
(Monilinia)
Leaf Spot
(Coccomyces)
Postharvest Decay
Brown Rot
(Phytophythora)
Post-harvest Decay
Blotch rot
(Acanthorhyncus)
Guigardia blight
Storage rots
Rates
AI Lb/100 Gal
or Lb/Acre
1.0
1.0
1.0
1.0
1.0
1.0
1.0-2.0
1.0-1.2
1.0-2.0
1.0-2.0
1.0
1.0
1.0
Limitations
25.0 ppm. No time
limits.
No time limitation.
25.0 ppm
do
No time Limitation.
25.0 ppm
do
No time Limitation.
100.0 ppm.
do
100.0 ppm
No time limitation.
Do not feed bypro-
ducts to diary
animals or animals
used for meat.
25.0 ppm.
Dip or Spray
25.0 ppm
do
do
do
-------
Crop or Site of Application
Dewberry
Grapes
Grapes (Raisins)
Mango
Nectarines
Table 19. (Continued)
Disease or Organism Controlled
Twig Blight
(Lophodermium)
Anthracnose
(Elsinoe)
Fruit Rot
Black Rot (Guigardia)
Botrytis Bunchrot
Dead Arm
(Cryptosporella)
Storage Rots
Mold, While Drying
Cercospora Leaf Spot
Molds and Storage Rots
Brown Rot
(Monilinia)
Coryneum Blight
(shothole)
Post-harvest Diseases
Scab (Cladosporium)
Rates
AI Lb/100 Gal
or Lb/Acre
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0-1.5
1.0
1.0-1.2
1.0
1.0
1.0-1.2
1.0
Limitations
No time limitation.
25.0 ppm
No time limitation.
25.0 ppm
do
No time limitation.
50.0 ppm
do
do
Do not apply within
5 days of a pre-
harvest application
of captan, 100.0
ppm.
50.0 ppm
Dip or spray. 50.0 ppm
No time limitations.
50.0 ppm
do
Dip or spray 50.0 ppm
No time limitation
50.0 ppm
-------
Crop or Site of Application
Oranges and Tangelos
Peaches
Table 19. (Continued;
Disease or Organism Controlled
Brown Rot
(Phythophthora)
Melanose (Diaporthe)
Scab (Elsinoe)
Brown Rot
Blossom Blight(Monilinia)
Post-harvest Decay
Rhizopus Rot
Pears
Scab (Cladosporium)
Shothole Blight
(Coryneum)
Crown Gall
Fruit Spot (Leptothyrium)
Rates
AI Lb/100 Gal
or Lb/Acre
1.0
do
do
1.0
1.0-1.2
1.0
1.0
1.0
2.0
1.0
Limitations
Do not apply after
fruit size exceeds
0.5 inches in dia-
meter. 50.0 ppm
do
do
No time limitation
or 6.0 Ibs/A and do
not apply within 1
day of harvest.
50.0 ppm
Dip or spray 50.0 ppm
No time limitation
or 6.0 Ibs/A. Do
not apply within 1
day of harvest
50.0 ppm.
do
do
None (non-food use)
Use in Mixture with
Sodium hypochlorite
200 ppm Chloride.
No time limitation.
25.0 ppm
Post-harvest Diseases
1.0-1.2
Dip or spray 25.0 ppm.
-------
Crop or Site of Application
Pineapples
Plums and Prunes
S3
VO
Quince
Raspberry
Strawberry
Table 19. (Continued)
Disease or Organism Controlled
Scab (Venturia)
Heart Rot(Phytophthora)
Root Rot(Phytophthora)
Storage and Transit Rot
Brown Rot (Monilinia)
Russet or lacy scab
(Cladosporium)
Brown Rot (Monilinia)
Scab (Venturia)
Anthracnose (Elsinoe)
Botrytis Blight
Fruit Rot
Spur Blight (Didymella)
Botrytis Rot
Rates
AI Lb/100 Gal
or Lb/Acre
1.0
5.0
2.0
5.0
1.0
1.0
5.0
5.0
1.0
1.0
1.0
1.0
1.5
Limitations
No time limitation.
25.0 ppm
No time limitation.
25.0 ppm
do
Dip or spray
25.0 ppm
No time limitation.
50.0 ppm
do
Do not apply within
7 days of harvest
25.0 ppm
do
No time limitation.
25.0 ppm
do
do
do
No time limitation-
25.0 ppm
Leaf Spots
1.5
do
-------
Crop or Site of Application
I.E. Agricultural Crops -
Vegetable Crops
Asparagus
Beans (Field and Snap)
Table 19. (Continued)
Disease or Organism Controlled
Beets
Cantaloupe, Cucumbers,
Honeydew Melon, Pumpkins,
Squash, (Summer and Winter)
and Watermelon
Botrytis Blight,
Phoma Rot,
Penicillium Rot,
Fusarium Rot
Anthracnose (Collectotrichum)
Downy Mildew(Phytophthora)
Rust (Uromyces)
Alternaria Leaf Spot
Cercospora Leaf Spot
Leaf Spots (septoria)
Angular Leaf Spot
(Psedomonas)
Anthracnose
(Marssonina)
Downy Mildew
(Pseudoperonospora)
Post-harvest Decay
Rates
AI Lb/100 Gal
or Lb/Acre
1.5
0.5
0.5
0.5
1.0
1.0
1.0
1.5
1.5
1.5
1.25
Limitations
Preplanting dip.
Non-food use
No time limitation-
25.0 ppm
do
do
No time limitation-
2.0 ppm
on roots, 100.0 ppm
on greens.
do
do
No time limitation.
25.0 ppm
No time limitation.
25.0 ppm
do
As dip or spray
25.0 ppm
-------
Crop or Site of Application
Carrots
Celery
Corn (Sweet)
Cucumbers (see Cantaloupes)
Eggplant
Lettuce
Table 19. (Continued)
Disease or Organism Controlled
Alternaria Blight
(Late Blight)
Cercospora Blight
(Early Blight)
Septoria Leaf Spot
Late Blight
(Septoria)
Pink Rot
(Sclerotinia)
Helminthosporium
(Leaf Blight)
Anthracnose
(Colletotrichum)
Fruit Rot
Early Blight
(Alternaria)
Phomopsis Blight
Downy Mildew (Bremia)
Rates
AI Lb/100 Gal
or Lb/Acre
1.0
1.0
1.0
1.0
1.0
0.75
1.0
1.0
1.0
1.0
1.0
Limitations
No time limitation.
2.0 ppm
do
do
No time limitation.
50.0 ppm
do
2.0 ppm
No time limitation.
25.0 ppm
do
do
do
No time limitation.
100.0 ppm
Onions (Green and Bulb-pre-
harvest)
Downy Mildew
(Peronospora)
1.0
No time limitation.
50.0 ppm on green
onions, 25.0 ppm
on dry
-------
Crop or^ Site of Application
Table 19. (Continued)
Disease or Organism Controlled
Rates
AI Lb/100 Gal
or Lb/Acre
Limitations
Purple Blotch
(Alternaria)
1.0
do
No time limitation.
Peppers, Pimentos
Potatoes
LO
ISJ
Rhubard (Greenhouse)
Spinach
Tomatoes
Molds, Storage Rots
Anthracnose
(Colletotrichum)
Cercospora Leaf
Spot and Stem-End Rot
Early Blight
(Alternaria)
Late Blight
(Phytophthora)
Storage rots
Seed-piece Treatment
(Browneye, Damping-off
and Verticillium)
Botrytis(Leaf rot)
Downy Mildew
(Peronospora)
Anthracnose
(Collettotrichum)
Early Blight
(Alternaria)
Grey Leaf Spot
(Stemphylium)
1.25
1.5
1.5
2.0-4.0
2.0-4.0
1.25
0.5-1.5
1.0
1.0
2.0
2.0
2.0
do
No time limitation.
25.0 ppm
do
No time limitation.
25.0 ppm
do
25.0 ppm
25.0 ppm
No time limitation-
25.0 ppm
100.0 ppm
No time limitation.
25.0 ppm
do
do
-------
Crop or Site of Application
I.C. Agricultural Crops
Table 19. (Continued)
Disease or Organism Controlled
Late Blight
(Phytophthora)
Septoria Leaf Spot
Rates
AI Lb/100 Gal
or Lb/Acre
2.0
2.0
Limitations
do
do
Ornamental Crops
Azaleas
Begonias
Camellias
Carnations
Chrysanthemum
Dichondra
Gladiolus
Roses
Petal Blight
(Ovulinia)
Damplng-of f
Damping-off
Powdery mildew (Erysiphe)
Petal Blight
(Sclerotinia)
Alternaria Leaf Spot
Damping-off
Rust(Uromyces)
Botrytis Flower Blight
Damping-off
Septoria Leaf Spot
White mold(Sclerotium)
Corm rot
Black Spot(Diplocarpon)
Botrytis Blight
2.0
2.0
2.0
0.11-0.22
0.5
1.0
2.0
1.0
1.0
2.0
1.0
1.0
2.0-7.5
1.0
1.0
None
None
None
None
None
None
None
None
None
None
None
None
None
None
-------
Crop or Site of Application
Grasses
Hollyhock
Lilacs
Snapdragon
Spdrea
Stock
II Soil Application
A. Agricultural Crops-
Vegetable Crops
Beets
Cantaloupe, Cucumber,
Honeydew Melon
Pumpkin, Squash and
Watermelon
Table 19. (Continued)
Disease or Organism Controlled
Brown Patch(Rhizoctonia)
Copper Spot(Gloeocercospora)
Damping-off
Leaf spots
Melting-out
(Helminthosporium)
Seedling Blight
Anthracnose
(Colletotrichum)
Anthracnose
Anthracnose
Anthracnose
Botrytis Blight
Root Rots
Rates
AI Lb/100 Gal
or Lb/Acre
1.0-2.0
3.3/A
Limitations
Non-pastured areas
only
do
do
do
do
do
2. I/A
2. I/A
2. I/A
2. I/A
4.0-5.0/A
do
do
do
do
do
None
None
None
None
None
Damping-off
Root rots
1.0
preplanting 2.0 ppm
on roots
preplanting 25.0 ppm
-------
Crop or Site of Application
Table 19. (Continued)
Disease or Organism Controlled
Rates
Limitations
Celery
Col lards
Corn (sweet)
Cucumbers
Eggplant
Kale, Collards
Mustard, Rutabagas, Turnips
Peppers
Spinach
Tomatoes
II. B. Agricultural Crops-
Field Crops
Cotton
Soybeans
II. C. Agricultural Crops-
Ornamental Crops
Azaleas
Flowers
Datnping-off
Damping-off
Damping-off
Root rot
Damping-off
Root-Rot
Damping-off
Damping-off
Damping-off
Damping-off
Damping-off
Root Rot
Damping-off
Damping-off
Petal Blight (Ovulinia)
Seed & Root Rot
AI Lb/100 Gal
or Lb/Acre
1.0
7.5/A
6.0/A
6.0/A
1.0
1.0
5.0-6.0
7.5/A
1.0
2.0-6.0/A
5.0-7.5/A
4.0-6.0/A
2.0-6.0/A
2.0
1.0
preplanting
prep Ian ting
preplanting
do
do
do
do
preplanting
on greens 2.
on roots
preplanting
preplanting
preplanting
50.0 ppm
2.0 ppm
2 . 0 ppm
2.0 ppn
0 ppm
25.0 ppm
100.0 ppm
planting 2.0 ppm
do
none
None
-------
u>
Os
Table 19. (Continued)
Disease or Organism Controlled
Rates
Limitations
Trees
Grasses
III. Seed Applications
Alfalfa
Barley
Beans
Beets (Sugar)
Bluegrass
Broccoli
Brussels Sprouts
Cabbage
Cantaloupe
Cauliflower
Clover
Collards
Corn (Field)
Corn(Sweet)
-• • •** — •— • •— — -
Damping-of f
Damping-off
Damping-of f
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
AI Lb/100 Gal
or Lb/Acre
1.0
1.0
AI 100 Lb Seed
0.4-6.0
0.6-2.0
0.2-3.0
0.6-9.6
2.2-6.0
0.4-2.25
0.4-2.25
0.4-2.25
0.8-2.25
0.4-2.25
2.2-6.0
0.4-1.8
0.5-1.8
0.8-3.75
None
None
Do not use treated
seed for food, feed
or oil purposes
non-food use.
do
do
do
do
do
do
do
do
do
do
do
do
do
-------
Table 19. (Continued)
Crop or Site of Application
Cotton
Cowpeas
Crucifers
Cucumbers
Flax
Grasses
Kale
Lespedeza
Milo
Muskmelon
Mustard
Oats
Onions
Disease or Organism Controlled
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Rates
AI 100 Lb Seed
0.75-4.0
0.8-2.25
0.4-1.8
0.7-2.2
1.0-2.2
2.2-9.0
0.4
2.2-6.0
0.8-3.0
0.5-1.5
0.3-2.2
0.6-5.63
0.75-16.0
Limitations
do
do
do
do
do
do
do
do
do
do
do
do
do
-------
Table 19. (Continued)
LO
oo
Crop or Site of Application
Peanuts
Pumpkins
Peas
Peppers
Rice
Rye
Safflower
Sesame
Sorghum
Soybeans
Spinach
Squash
Swiss Chard
Disease or Organism Controlled
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Rates
AI 100 Lb Seed
0.4-6.0
0.5-1.54
0.8-3.0
0.8-2.25
0.9-3.75
0.6-3.2
0.3-1.9
0.75-1.6
0.5-2.4
0.7-3.0
1.8-4.5
0.5-1.54
3.4-9.0
Limitations
do
do
do
do
do
do
do
do
do
do
do
do
do
-------
Co
VQ
Crop of Site of Application
Table 19. (Continued)
Disease or Organism Controlled
Rates
House Plants
Home Gardens
non-specified
do
Variable
do
Limitations
Tomato
Trefoil
Turnips
Watermelons
Wheat
,IV, Miscellaneous Agricultural Uses
Packing Boxes
Soil and Greenhouse
Bench Preplanting Treatment
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Seedling Diseases
Storage Rots
Damping-off
Root Rots
AI 100 Lb Seed
0.8
2.2-6.0
0.4-1.5
0.5-1.54
0.4-3.0
Lb or %
1.0/100 gallons
5.0-6.0 Ibs/A
do
do
do
do
do
None
None
None
As with specific
agricultural uses
-------
Crop or Site of Application
IV. Home Environment -
Table 19. (Continued)
Disease or Organism Controlled
Rates
Lb or "/,
Limitations
Inside and Outside
Paints
Surfaces
V. Industrial Uses
Cosmetics and Pharmaceuticals
Lacquers, Paints (oil based)
Paper
Paste (Wallpaper Flower)
Plasticizers
(Fungicidal Plastics)
Polyethylene
Rubber Stabilizer
Textiles
Vinyl
Mildew
Fungi
Fungi
Fungi
Mold & Mildew
Mold & Mildew
Fungi
Mold & Mildew
Mold & Mildew
Molds & Mildew
Mildew
1.0 oz/gal
0.31%
by weight
0.1-0.5%
by weight
0.52-2.1%
by weight
0.15-0.90%
by weight
0.225%
by weight
0.225%
by weight
0.44-1.74%
by weight
0.44-1.75%
by weight
0.90-1.7Z
by weight
0.44-0.90%
by weight
Control on painted
surfaces
None
None
None
None
None
None
None
None
None
None
-------
Table 20. REGISTERED USES OF CAFTAN 507. WETTABLE POWDER-
CROPS AND OTHER USES, DISEASES CONTROLLED
DOSAGE RATES, AND USE LIMITATIONS
(FUNGICIDE)
Active Ingredient By Wt.
*Captan _ 50%
Inert Ingredients __ 50%
*N-f(trichloromethyl)thio]-4-cyc!ohexene-1,2-dicarboximide.
Not licensed for use or export outside of the United States, its
territories and possessions, Canada or Mexico.
READ ENTIRE LABEL. USE STRICTLY IN ACCORDANCE WITH CAUTIONS
AND DIRECTIONS, AND WITH APPLICABLE STATE AND FEDERAL REGULA-
TIONS.
KEEP PESTICIDE IN ORIGINAL CONTAINER. DO NOT PUT CONCENTRATE
OR DILUTE INTO FOOD OR DRINK CONTAINERS.
STORE IN COOL, DRY PLACE. PROTECT FROM EXCESSIVE HEAT.
BURN BAG IMMEDIATELY WHEN EMPTY. STAY OUT OF SMOKE.
NOTE: For concentrate sprayer applications, apply the same quantity (per
acre) of ORTHOCIDE 50 Wettable in sufficient water for coverage as would
be normally applied when spraying dilute mixture.
APPLES: Primary Scab Infection—11/2 to 2 Ibs. per 100 gals, spray. Second-
ary Apple Scab, Brooks Fruit Spot, Flyspecking—1 Ib. per 100 gals, spray.
Severe Infection—2 fbs. per 100 gals, spray. Bitter Rot, Black Rot, Botryos-
phaeria. Black Pox—2 Ibs. per 100 gals, spray. Bull's Eye Rot, Botrytis Rot
—2 Ibs. per 100 gals, spray. Make 1 or 2 applications with late cover
sprays and 1 or 2 preharvest applications. Special Sooty Blotch Sprays
(August and September}—1 Ib. ORTHOCIDE 50 Wettable and 1 Ib. ORTHO
Zineb Wettable per 100 gals, spray. Where lead arsenate has been used
in the apple maggot cover sprays, use ORTHOCIDE 50 Wettable at 2 Ibs.
per 100 gals, spray. Do not use lead arsenate within 30 days of harvest.
ORTHOCIDE 50 Wettable should not be used in combination with or closely
following or in alternation with wettable sulfur products on sulfur sensitive
varieties of apples such as Red Delicious, Stayman, Baldwin, King, etc. as
severe foliage injury and defoliation may occur.
APRICOTS: Brown Rot (Twig Blight), Jacket Rot—2 Ibs. per 100 gals, spray.
Apply at red bud stage, bloom and repeat at 75 per cent petal fall.
ALMONDS: Brown Rot. Shot Hole, Scab, Leaf Blight-2 Ibs. per 100 gals.
spray. Apply at popcorn, bloom, petal fall stages and up to 5 weeks after
petal fall. May be used up to 12 days of harvest if hulls are not fed to
dairy animals or animals being finished for slaughter.
NET WEIGHT
Chevron Chemical Company
Ortho Division/San Francisco, Calif. 94119
Richmond, California Fresno, California
Des Moines, Iowa Cherry Hill, New Jersey Orlando, Florida
Form 3640-Y2 Product 1760 Made in U.S.A.
EPA Reg. No. 239-533-AA
Source: Chevron Chemical Company, San Francisco, Calif.
141
-------
Table 20. (Continued)
ASPARAGUS: Preplanting Root Dip—Stimulation of shoot growth—3 pounds
to 100 gals, spray. Dip root sections for 1 minute, drain and plant.
GRAPES: Downy Mildew, Blackrot—2 Ibs. in 100 gals, spray. Apply just
before bloom, repeat immediately after bloom. Depending upon suscepti-
bility of grape variety, from 1 to 3 more sprays may be needed at 7 to
10-day intervals. For late season control on foliage, use ORTHO Copper 53
Fungicide. GRAPES: Dead Arm Disease (California)—2 Ibs. per 100 gals.
spray, 3 to 6 Ibs. per acre. First spray at bud break to 1" shoot length.
Second Spray 2 weeks later or shoots 4 to 8" in length, at 4 to 6 Ibs. per
acre. (Northeast)—2 Ibs. per 100 gals, spray. Make first application when
new growth is 4 to 6" long, repeat when growth is 8 to 10 inches long.
PEACHES, NECTARINES: Brown Rot, Scab, Coryneum (Shot Hole)—2 Ibs.
per 100 gals, spray. Apply at pink bud, full bloom and petal fall stages.
Repeat at 10 to 14-day intervals after petal fall. Also make late fall appli-
cations for Coryneum Blight.
PEARS: Pear Scab (Except Pacific Northwest)-PRIMARY INFECTION-2 Ibs.
per 100 gals, spray. Apply during early finger stage and Petal Fall stage.
SECONDARY INFECTION-1 Ib. per 100 gals, spray during cover sprays.
Severe Scab Infection—2 Ibs. per 100 gals, spray. Repeat as necessary.
Russeting may be reduced on Bosc Pears. Do not use on D'Anjou Pears.
CHERRIES: Cherry Leaf Spot (West only), Brown Rot, Botrytis Rot—2 Ibs. per
100 gals, spray. Spray at prebloom, bloom, petal fall.
RASPBERRIES: Spur Blight, Anthracnose-2 Ibs. to 100 gals, spray. Apply
when blossoms are in bud (young canes are 8 to 10 inches long). Make
second application 2 weeks later. Apply a fall spray after old canes are
removed. Thorough coverage is essential. Fruit Rot—2 Ibs. to 100 gals.
spray. Make 3 applications as follows. First—3 to 5 days before harvest
starts; Second—At mid-harvest; Third—8 to 10 days after second application.
STRAWBERRIES: Botrytis Rot-2 to 3 Ibs. to 100 gals, spray. (200 diluted
gals, per acre or equivalent of 4 to 6 Ibs. per acre in water to cover).
Apply when new growth starts in spring before fruit starts to form. Repeat
weekly. Severe Infection—Continue through harvest period, treating imme-
diately after each picking.
PRUNES, PLUMS: Brown Rot-2 Ibs. per 100 gals, spray. Apply at Green Tip
or popcorn stage. Repeat at bloom and 75% petal fall stages. Also repeat
later in season as necessary. Prune Russet Scab (Lacy Scab in California)—
READ THE LABEL
KEEP OUT OF REACH OF CHILDREN.
^-/"AvJ I iv-'lNt Avoid inhalation of dust or spray mist. Avoid
contact with skin. Do not store or transport near feed or food. Foliage
injury may at times occur to Red Delicious, Winesap and other sensitive
varieties of apples in early season sprays. Do not apply under conditions
involving possible drift to food, forage or other plantings that might be
damaged or the crops thereof rendered unfit for sale, use or con-
sumption.
This product is toxic to fish. Keep out of lakes, streams or ponds.
142
-------
Table 20. (Continued)
2 Ibs. per 100 gals, spray (8 Ibs. per acre). Apply at full bloom.
LETTUCE, SPINACH: Downy Mildew-2 Ibs. per 100 gals, spray (100 to
200 gals, spray per acre). Apply at first sign of disease. Repeat at 7 to 10-
day intervals as necessary to maintain control.
TOMATOES: Early Blight, Late Blight, Gray Leaf Spot, Anthracnose, Septoria
Leaf Spot—2 Ibs. per 100 gals, spray or apply 4 to 6 Ibs. per acre in water
to cover. Severe Infection: 4 Ibs. per 100 gals, spray or apply 6 to 8 Ibs. per
acre in water to cover. Apply at first sign of diseases. Repeat at 5 to 7-day
intervals or as necessary to keep diseases under control.
CANTALOUPES, CUCUMBERS, SUMMER AND WINTER SQUASH, WATER-
MELONS. PUMPKINS: Anthracnose, Downy Mildew-2 Ibs. per 100 gals.
spray or apply 4 Ibs. per acre in water to cover. Apply at first sign ol
disease. Repeat at 5 to 7-day intervals or as necessary.
CELERY: Late Blight (Septoria), Pink Rot (Sclero:inia)-2 Ibs. per 100 gals.
spray. Apply 200 diluted gallons per acre or equivalent of 4 Ibs. per acre in
water for coverage. Apply at first signs of diseases. Repeat at 7 to 10-day
intervals as necessary to maintain control.
TURF, LAWN: Brown Patch, Leaf Spot, Damp-Off, Root Rot—2 Ibs. per 100
gals, spray. Apply 10 gals, to each 1000 sq. ft. of turf or apply 8 Ibs. per
acre in water for coverage. Apply prior to infection. Repeat at 7 to 10-day
intervals as necessary.
LEMONS, LIMES, ORANGES, GRAPEFRUIT: Brown Rot (Phytophthora)-2 to
4 Ibs. to 100 gals, spray. Apply as a skirt spray prior to winter rains, thor-
oughly wetting tree to heights of 3 to 4 feet. Re-treat 10 weeks after first
application. ORANGES, TANGELOS: Scab, Melanose, Tree Response such
as increased Fruit Set—Apply 10 Ibs. in combination with 2'/2 pts. CHEVRON
Spray Sticker per 500 gals, in the Post-Bloom spray from % petal fall un-
til fruit reaches approximately Vj inch in diameter. NOTE: Apply ORTHO
Copper 53 Fungicide in Dormant Spray as primary scab spray. For fresh
fruit melanose control, apply ORTHO Copper 53 Fungicide as a second
Post-bloom spray 5 to 6 weeks after petal fall. For maximum tree response
and scab control, use ORTHOCIDE 50 Wettable as near Petal Fall as pos-
sible. Do not feed treated raw citrus by-products to livestock.
BEANS, PEAS: Damp-off on Beans, Root Rot on Beans and Peas—Broadcast
10 to 12 Ibs. per acre. Work into upper 3 or 4 inches of soil or apply 5 to 6
Ibs. per acre in row at planting time.
COMPATIBILITY: ORTHOCIDE 50 Wettable may be combined with most
commonly used insecticides, adjuvants and fungicides with the exception
of strongly alkaline materials such as hydrated lime, which reduces the
fungicidal activity. Do not use this product in combination with oil sprays
or with solvent formulations of Parathion products. Do not use this product
on foliage closely following oil sprays .
CONDITIONS OF SALE: 1. Chevron Chemical Company (Chevron) warrants
that this material conforms to the chemical description on the label and
is reasonably fit for use as directed hereon. Chevron neither makes, nor
authorizes any agent or representative to make, any other warranty of
FITNESS or of MERCHANTABILITY, guarantee or representation, express
or implied, concerning this material.
2. Critical and unforeseeable factors beyond Chevron's control prevent it
from eliminating all risks in connection with the use of chemicals. Such
risks include, but are not limited to, damage *o plants and crops to which
the material is applied, lack of complete conlrol, and damage caused by
drift to other plants or crops. Such risks occur even though the product is
reasonably fit for the uses stated hereon and even though label directions
are followed. Buyer and user acknowledge end assume all risks and lia-
bility (except those assumed by Chevron under 1 above) resulting from
handling, storage, and use of this material.
143
-------
Table 20 is a copy of the label of a widely used captan formulation,
registered by the Ortho Division of Chevron Chemical Company, the largest
formulator and marketer of captan (EPA Registration Number 239-533-AA).
As this label indicates, the directions for use of captan are quite complex
and differ considerably from crop to crop.
The registration data on captan presented in Tables 19 and 20 indi-
cate that this product is a broad spectrum fungicide useful in the control
of foliage diseases of many fruit, vegetable and ornamental cuttings and
bulbs; for the control of some diseases on turf and lawns; as a seed pro-
tectant; and as a potato seed piece treatment for control of rots.
State Regulations - Captan is one of the less toxic synthetic pesticides,
rated "slightly toxic" for labeling purposes. Captan is not currently
subject to specific use restrictions under state pesticide laws or regu-
lations. Seed treatment uses of captan may be subject to state laws
covering this area, including such matters as coloring and labeling of
treated seeds, etc.
Production and Domestic Supply
Volume of Production - According to the United States Tariff Commission's
synthetic organic reports, there has been only one basic source of pro-
duction of captan in the United States in recent years, up to and including
1972, i.e., Stauffer Chemical Company's Calhio Chemicals Division plant
located in Perry, Ohio (a unit operated jointly by Stauffer and the Ortho
Division of Chevron Chemical Company).
In the Tariff Commission's reports, the production and sales volumes
of captan are not reported individually. In the most recent report, cover-
ing calendar year 1972—', captan is included in a category identified as
"all other cyclic fungicides." In addition to captan, this group includes
six other specific cyclic fungicides; tri- and tetra-chlorophenols; and
additional, unspecific cyclic fungicides. The production volume for
this composite group in 1972 was reported at 45,360,000 Ib of active
ingredients.
Through a process of careful analysis of the production and use
patterns of all organic fungicides in this group, supported by information
from trade sources, Midwest Research Institute developed estimates on the
volume of production of all major products in the group. The estimated
volume of production of captan in 1972 is 17 million pounds of active
ingredient (AI).
I/ U.S. Tariff Commission, Synthetic Organic Chemicals, U.S. Production
and Sales, 1972, TC Publication 681 (1973).
144
-------
Imports - Imports of pesticides that are classified as "benzenoid chemicals"
(this group would include captan) are reported in a 1973 U.S. Tariff
Commission annual report.I' According to the report, there were no imports
of captan into the United States in 1972.
Exports - Pesticide exports are reported by the Bureau of the Census
annually. Technical (unformulated) captan is included in this report in
Schedule B, Section 512.0610, a category including all technical synthetic
organic fungicides. Formulations of captan are included in Schedule B,
Section 599.2055, entitled "Captan and Mercury Fungicidal Preparations,
Except Household and Industrial."!/
Total exports of organic fungicides in these two categories for 1972
were as follows:
Section 512.0610 (Technical Synthetic Organic Fungicides)
8,111,219 Ib.
Section 599.2055 (Captan and Mercury Fungicide Formulations)
761,875 Ib.
To derive the 1972 export volume of captan from these composite
totals, we made a thorough analysis of these two pesticide export cate-
gories by unit dollar values and by countries of destination. In the
next step this information was matched against our knowledge of the crop
protection problems and the pesticide trading patterns of the countries
of destination. Additional information was obtained from trade contacts,
from the U.S. Agency for International Development (AID), and from other
sources. Based on all data and information obtained in this manner,
Midwest Research Institute estimates the 1972 export volume of captan at
1.0 million pounds AI.
Domestic Supply - The estimated domestic supply of captan in the United
States in 1972 was as follows, based on the data presented in the preced-
ing three sections:
17 U.S. Tariff Commission, Imports of Benzenoid Chemicals and Products,
TC Publication 601 (1973).
2J U.S. Bureau of the Census, U.S. Exports, Schedule B, Commodity by
Country, Report FT 410.
145
-------
U.S. Production 17.0 Million Ib AI
Imports None or negligible
Exports 1.0 Million Ib AI
Domestic Supply 16.0 Million Ib AI
Comparable estimates for 1973 cannot be made at this time because
the U.S. Tariff Commission report on the production and sales of pesti-
cides in 1973 will not be published until the fall of 1974.
Formulations - Captan is available to users in the United States in a
great variety of dry formulations, i.e., wettable powders and dusts of
various concentrations. An aqueous suspension captan formulation is
available on the market at the present time.
The basic producer of captan, Stauffer Chemical Company, sells a
substantial share of its production to fonnulator-customers in the form
of technical or manufacturing concentrates. The largest formulator by far
is the Ortho Division of Chevron Chemical Company. Ortho and some other
formulators then prepare and sell formulations containing captan under
their own labels and brand names to end users, either directly, or through
wholesalers and/or retailers. Stauffer Chemical Company also prepares and
markets formulated captan products.
Frear (1972)_L/ lists the following pesticide products containing cap-
tan as the only active ingredient:
13 Dust formulations (ranging in concentration from 5.0-25.0%; 7.5%
apparently the most popular strength)
1 Dust base concentrate (90.0%.)
6 Wettable powders (five of these 50% AI; one 80%)
2 75%, Seed treatment formulations (for slurry treaters)
2 Manufacturing concentrates for industrial and pharmaceutical purposes.
In addition to these products containing captan as the only active
ingredient, a number of combination formulations, primarily dusts, are
listed in which captan is combined with other fungicides and/or insecti-
cides, for foliar application, seed treatment, and related uses.
_!/ Frear, D. E. H., Pesticide Handbook-Entoma, 24th ed., College Science
Publishers, State College, Pa. (1972).
146
-------
Since the 1972 edition of the Pesticide Handbook was put together,
a number of additional captan formulations have become available, es-
pecially seed treatment products. For instance, as of the spring of 1974,
the Ortho Division of Chevron Chemical Company carried the following cap-
tan products in its line:
Sprayable formulations for foliar applications;
Captan 50% wettable powder
Captan 80% wettable powder
Captan 40% - zineb 30% wettable powder
Captan 15% - malathion 7.5% - methoxychlor 15% wettable powder
Dust formulations for foliar applications;
Fungicides only;
Captan dusts containing 5, 7.5, 10, and 15% of AI
Captan-sulfur combination dusts in seven different ratios i.e.,
5-50; 7.5-25; 10-10; 10-25; 10-50; 15-25; and 15-40
Captan 10% - Botran 5% - sulfur 40% dust
Fungicide - insecticide combinations;
Captan 5% - naled 6% dust
Captan 10% - naled 4% dust
Captan 5% - endosulfan 2% dust
Captan 5% - Omite 3% dust
Captan 5% - naled 3% - carbaryl 7.5% - sulfur 25% dust
Captan 5% - methoxychlor - 5% - rotenone 0.75% - other cube
resins 0.75% dust
Seed protectant and soil treatment formulations;
Fungicide(s) only, seed treatment:
Captan 5%, 10% and 15% dusts for potato seed piece treatment
Captan 25% dusts for soybean and peanut seed protection
Captan 65% seed protectant dust (peas)
Captan 75% seed protectant dust (many crops)
Captan 75% seed protectant for slurry treatments (many crops)
Captan 38% (4 Ib/gal) flowable seed protectant (many crops)
Captan 25% seed protectant with molybdenum (soybeans)
Captan 20% - hexachlorobenzene 40% (wheat)
Captan 35% - Botran 35% (peanuts)
Captan 60% - Botran 20% seed protectant (peanuts
147
-------
Captan 7.5% - Streptomycin 0.01% (potato seed pieces)
Captan 10% - pentachloronitrobenzene 20% (dust for infurrow or
planter box use on cotton)
Fungicide - insecticide combinations, seed treatment:
Captan 60% - dieldrin 15% (many crops, slurry treatment)
Captan 12.5% - lindane 25% (many crops)
Captan 60% - lindane 15% (many crops)
Captan 65% - methoxychlor 5% (peas)
Captan 65% - methoxychlor 10% (many crops)
Captan 75%, - methoxychlor 3% (many crops)
Captan 75% - methoxychlor 5%> (many crops)
Captan 10% - diazinon 30% (some field crops)
Fungicides - soil treatment;
Captan 10% - pentachloronitrobenzene 10% soil fungicide (several
crops)
Captan 30% - pentachloronitrobenzene 30% soil fungicide (several
crops)
The sprayable and dust formulations for foliar application are regis-
tered for use on a wide variety of crops. The many different strengths
and combinations of active ingredients are designed to meet a variety of
growers' needs in different parts of the country. In the case of the seed
protectant and soil treatment preparations, products designed for specific
crops have been so identified in the above list.
According to information from several major captan formulators and
marketers, the 50 and 80% wettable powder formulations and the 7.5 to 15%
dust formulations are the most widely used formulations of captan.
Use Patterns of Gaptan in the United States
General - Captan is a broad spectrum contact fungicide effective against
a fairly wide range of fungi causing plant diseases. It acts by inhibiting
fungus mycelial growth. Captan does not cure or eradicate fungal infec-
tions on plants after they have become established and has to be applied
prior to establishment of fungal infections.
Captan is registered and recommended for the control of foliage dis-
eases on many fruit, vegetable, and ornamental crops; as a dip for the
control of rots and damping off of cuttings, bulbs, and other planting
stock; for the control of certain diseases on lawns and turf; for the
control of rots of potato seed pieces, and as a protectant for the con-
trol of rots and damping off on many types of seeds.
148
-------
In a project sponsored jointly by the Environmental Protection Agency
and the Council on Environmental Quality (Midwest Research Institute-RvR
Consultants, 19741/) the production, distribution, use, and environmental
impact potential of 25 selected pesticides, including captan, were studied.
In that study, it was determined that about 10.0 million pounds of captan
AI were used for agricultural purposes in 1972. The manufacturers indi-
cated that 1.0 million pounds were used for the home and garden sector.
There were no significant uses of captan fy industrial, commercial or
industrial organizations, or by governmental agencies.
Agricultural Uses of Captan - Surveys on the use of pesticides by farmers
in the United States were conducted by the U.S. Department of Agriculture
in 1964, 1966, and 1971 (Agricultural Economic Reports No. 131, published
in 1968; No. 179, published in 1970; and No. 252, publisned in 1974).
Table 22 summarizes the farm uses of captan from these surveys. It
appears that the level of use of captan by farmers has remained relatively
constant during the period covered by three USDA surveys. Estimates of
the agricultural uses of captan in 1972 were developed by RvR Consultants
used in the MRI-RvR study are also shown in Table 22. Although the 1972
usage appears to be greater, the USDA data is not directly comparable to
the RvR estimates.
The USDA data is derived from interviews with farmers in selected
counties throughout the United States. These interviews were conducted
in nationwide programs whose principal purpose was the collection of data
on farm production expenditures. The original, raw pesticide data were
then expanded and adjusted by specific factors to translate them from the
survey sample to the national universe. The USDA authors point out that
the reliability of their data is related to the quantity of pesticides
used, the number of acres treated, and the importance of the crop in the
region. They state that the relative distribution of pesticides among
crops and regions shown in their reports is more reliable than absolute
quantities for individual crops and regions. Compared to all agricultural
pesticides, captan is not one of the major products in regard to volume
of use, and its use is scattered over many different crops, and over all
regions of the country. Thus, there are many potential sources of error
multiplication and/or extrapolation from too small a data base in a survey
of this type.
The RvR estimates, on the other hand, were obtained by starting out
with the estimated total domestic supply of captan. Based on information
from trade sources, MRI estimates that captan stocks in inventory at the
beginning of 1972 were very similar in size to those at the end of the
year; the domestic supply of captan is assumed to be equal to domestic
consumption. Manufacturer estimates indicate that about 1.0 million Ib
_!/ Midwest Research Institute/RvR Consultants, "Production, Distribution,
Use and Environmental Impact Potential of Selected Pesticides,"
(Draft), Council on Environmental Quality Control, Contract No. EQC-
311 (March 1974).
149
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Table 21. FARM USES OF CAPTAN IN THE U.S. IN 1964, 1966, 1971, AND 1972
Year
1972 1971 1966 1964
RvRl/ USDAk/ US DA a./ US DA-/
Source Thousands of pounds of active ingredient
Crops 9,600 6,013 6,587 5,661
Other farm uses 400 477 282 12
Total farm uses 10,000 6,490 6,869 5,673
a/ RvR estimates. See text.
b/ USDA reports on "Quantities of Pesticides Used by Farmers," in 1964
(Agricultural Economic Report No. 131, published 1968); in 1966
(Agricultural Economic Report No. 179, published 1970); in 1971
(Agricultural Economic Report No. 252, in press).
of captan active ingredient were used in the home and garden sector in
1972. Since there were no significant uses of captan in the industrial/
commercial sector or by Governmental agencies, MRI estimates that approxi-
mately 10-14 million pounds of active ingredient must have been used in
agriculture.
In comparing this estimate to the USDA figures (Table 21), MRI does
not believe that there was a 50% increase from 1971 to 1972 in the level
of use of captan. MRI believes that the USDA surveys have tended to under-
state the actual quantities of captan used by farmers in the U.S.
150
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Table 22 presents a further breakdown of the farm uses of captan in
1972 by regions and by major crops, based on RvR estimates developed in
the MRI-RvR study. The following information sources were used in
arriving at these estimates:
1. The three USDA surveys of pesticide uses by farmers mentioned
above;
2. The annual USDA publication "Pesticide Review" (Agricultural
Stabilization and Conservation Service);
3. Results of a survey of the Federal/State Cooperative Extension
Services in all 50 states and in Puerto Rico conducted by RvR
Consultants in 1973;
4. Analyses of state pesticide use recommendations;
5. Local and regional estimates on pesticide use volumes obtained
from State Research and Extension personnel in personal communi-
cations;
6. Pesticide use reports from the states of Arizona, California,
Illinois, Indiana, Michigan, Minnesota, and Wisconsin;
7- Data on pesticide uses supplied by the EPA Community Pesticide
Studies Projects in Arizona, Hawaii, Idaho, Mississippi, South
Carolina, Texas, and Utah;
8. Estimates and information obtained from basic producers of captan
and other pesticides, and from pesticide trade sources;
9. Pesticide use surveys conducted recently by Wallaces' Farmer,
Des Moines, Iowa; Prairie Farmer, Chicago, Illinois; and
Wisconsin Agriculturist, Madison, Wisconsin; and
10. "Agricultural Statistics," an annual publication of the U.S.
Department of Agriculture.
Data from all of these diverse sources was carefully analyzed, cor-
related, and cross-checked to arrive at the final estimates.
151
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Table 22, ESTIMATED FARM USES OF CAPTAN IN THE U.S. BY REGIONS AND
MAJOR CROPS (1972)
Thousands of pounds of active ingredient
Region
Northeast-
Southeast-'
c/
North Central-
South Central-/
Northwest-/
Southwest-'
Total, all
regions
Apples
2,200
1,100
1,400
Negligible
1,000
Negligible
5,700
All other
fruits
and nuts
1,050
800
400
350
500
300
3,400
Vege-
tables
150
Negligible
100
50
100
Negligible
400
All other
farm
uses
100
100
100
100
100
Negligible
500
Totals,
All f arm
uses
3,500
2,000
2,000
500
1,700
300
10,000
a/ Maine, New Hampshire, Vermount, Massachusetts, Rhode Island, Connecticut,
New York, New Jersey, Pensylvania.
b/ Maryland, Delaware, Virginia, West Virginia, North Carolina, South
Carolina, Georgia, Florida.
c_/ Ohio, Indiana, Illinois, Michigan, Wisconsin, Minnesota, Iowa,
Missouri, North Dakota, South Dakota, Nebraska, Kansas.
d/ Kentucky, Tennessee, Arkansas, Louisiana, Mississippi, Alabama,
Oklahoma, Texas.
e/ Montana, Idaho, Wyoming, Colorado, Utah, Washington, Oregon, Alaska.
tj New Mexico, Nevada, Arizona, California, Hawaii.
Source: RvR estimates. See text.
152
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Farm Uses of Captan by Regions - As previously mentioned, MRI esti-
mates that about 10-14 million pounds of captan AI were used in agricul-
ture in the U.S. in 1972 (Table 21). Of this total, the Northeastern
states used about 3.5 million pounds, primarily on apples, other deciduous
fruits, and small fruits. The Southeastern and North Central states used
approximately 2 million pounds of captan each, followed by the Northwestern
states (1.7 million pounds). The South Central (500,000 Ib) and South-
western (300,000 Ib) states accounted for the balance.
Farm Uses of Captan by Crops - In analyzing the agricultural uses
of captan by commodities (Table 22), it is obvious that this product is
primarily a fruit fungicide. The use of captan on apples accounts for more
than one-half of the total quantity used in agriculture in 1972. The larg-
est use of captan on apples was in the Northeastern states (2.2 million
pounds), followed by the North Central (1.4 million pounds), the South-
eastern (1.1 million pounds), and the Northwestern (1 million pounds)
states.
All other fruits and nuts (including citrus fruits, deciduous tree
fruits other than apples, small fruits and berries, etc.) accounted for
another 3.4 million pounds of captan consumption. The uses of captan on
"all other fruits and nuts" were distributed regionally in much the same
manner as the uses on apples. The largest quantity of captan in this cate-
gory was used in the Northeastern states (1,050,000 Ib), followed by the
Southeastern states (800,000 Ib). The remaining four regions each ac-
counted for 500,000 Ib or less.
Captan uses on all fruit and nut crops combined made up more than
90% of the total farm use of the product in 1972.
Uses of captan on vegetables, and for all other purposes combined
totaled about 900,000 Ib, distributed fairly evenly over all regions of
the country. "All other uses" include foliar uses of captan on crops other
than fruits and vegetables, uses for the protection of many types of seeds
against rots and damping off; as a dip for control of rots and damping
off of ornamental and horticultural planting stock; as a treatment for
the control of rots on potato seed pieces, for the treatment of fruit and
vegetable packing boxes against storage molds, etc.
153
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Home and Garden Uses of Captan - Manufacturer estimates indicate that
about 1.0 million pounds of captan AI were used by home gardeners in the
U.S. in 1972. The use patterns of captan in this area were not investi-
gated by MRI. No other published quantitative data is known to be avail-
able on nationwide home and garden pesticide uses.
In the home garden field, captan is widely used for the control of
diseases on roses, other flowers, home-grown vegetables and fruits, and
lawns. It is registered and recommended against blackspot on roses;
powdery mildew, rust, leaf spot and other diseases on other flowers;
against brown patch, leaf spot, damp-off, root rot and melting out on
lawns; against blights and leaf spots on tomatoes and other vegetables;
against scab, rots and leaf spots on apples, pears, stone fruits; and
strawberries, and against similar fungal diseases on other homegrown
ornamental and horticultural plants.
Nearly all retail outlets for home and garden pesticides throughout
the entire U.S. carry one or more formulations containing captan.
Captan Uses in California - The Statei' keeps detailed records of pesti-
cide uses by crops and commodities which are published quarterly and
summarized annually. Table 23 lists the uses of captan in California
by major crops and other uses for the 4-year period (1970-1973) .
In California, captan is not subject to the special restrictions and
reporting requirements imposed upon the sale and use of pesticides desig-
nated as "injurious materials." For this reason, the California Department
of Agriculture's statistics are probably less complete for captan than
for restricted pesticides. However, the Department and others familiar
with pesticide uses in California believe that these statistics include
a substantial share of the captan actually used. Thus, while the data
for individual and total uses may not be complete, they do provide a
good indication for the use patterns of captan on California crops.
According to these state reports (Table 23), the total use volume of
captan in California varied considerably, i.e., from a low of 115,000 Ib
in 1972 to a high of 292,000 Ib in 1973. Similar variations occurred in
the use of captan on individual crops.
Stone fruits (apricots, cherries, nectarines, peaches, plums, prunes)
appear to account for the single biggest share of the total use of captan
in California agriculture. Substantial quantities of the product are also
used on grapes, almonds, walnuts, and strawberries. Uses on tomatoes, many
other smaller crops, and some noncrop uses make up the balance.
I/ California Department of Agriculture, Pesticide use reports for 1970,
1971, 1972 and 1973.
154
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Table 23. CAPTAN USES IN CALIFORNIA BY MAJOR CROPS AND OTHER USES
(1970-1973)
Thousands of pounds of active ingredient
Crop
Stone fruits^'
Almonds, walnuts
Strawberries
Grapes
Tomatoes
All other crop uses
Noncrop uses
Totals, all uses
Year
1973
118
48
11
52
8
39
16
292
1972
29
14
11
28
9
17
7
115
197L
33
4
12
24
10
59
1
143
1970
135
37
7
8
4
14
5
210
a./ Apricots, cherries, nectarines, peaches, plums, prunes, etc.
Source: California Department of Agriculture, op. cit. (1970
through 1973).
Tables 24 and 25 present the captan uses in California in detail,
(by crops and other uses, number of applications, pounds of active in-
gredient, and number of acres treated) for 1972 and 1973, the two most
recent years for which such data are available. In both years, captan
was used in California on about 60 different crops.
The California Department of Agriculture's captan statistics cover
primarily captan uses by farmers. They probably include very little of
the captan used in the home and garden field.
At the present time, no other state records or publishes pesticide
use data in comparable detail,, Limitations of time and resources
available for this task did not permit development of estimates on the
uses of captan by states, crops, and other uses, beyond the detail
provided in Tables 21 and 22.
155
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Table 24. USE OF CAPTAN IN CALIFORNIA IN 1972, BY CROPS,
APPLICATIONS, QUANTITIES , AND ACRES TREATED
Commodity Applications Lb
U
P
P
P
P
Alfalfa
Almond
Apple
Apricot
- Asparagus
Barley
- Barley for seed
Beans, dry edible
- Beans, dry edible
Beans , green or forage
- Beans for seed
Berries
Boysenberry
Cabbage
Celery
Cherries, sweet
Citrus
City agency
Co Hard
Cotton
County or city parks
Cucumber or pickle
Grapefruit
Grape
Lettuce, head
Lettuce, leaf
Nectarine
Onion, dry
Orange
Ornamentals
Ornamental bedding plants
Other agencies
Pasture, range land
Peach
Pear
3
70
1
12
2
2
3
3
5
1
13
6
3
6
39
4
11
2
6
2
6
112
56
21
31
13
17
2
5
1
145
3
116.46
12,316.03
2.50
2,149.20
195.00
388.82
64.50
528.00
436.17
192.50
928.50
235.75
261.00
55.00
1,234.79
85.00
16.39
12.00
10.50
1,793.17
2.27
86.89
391.53
27,790.12
1,480.65
321.50
1,940.44
155.92
532.76
1.00
30.50
6,510.00
3.12
18,588.49
312.50
Acres*
124.00
2,079.50
5.00
538.00
1,350,000
361,700
60,000
176.00
450,300
55.00
8,373,650
155.50
87.00
52.00
685.50
20.00
144.20
6.00
1,156.00
22.00
95.40
8,917.00
1,027.90
229.25
471.50
253.50
406.20
0.50
30.50
79.00
3,550.60
75.00
156
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Table 24. (Continued)
Commodity
Pea
Pepper, bell
Plum
Potato
Prune
Raspberry
Residential control
Rice
P - Rice
School district
P - Sorghum for seed
Spinach
Squash, summer
State highway
Strawberry
Structural control
P - Sudangrass for seed
Tomato
University of California
Vector control
Walnut
P - Wheat for seed
Total
Applications
1
1
10
1
19
1
1
1
7
34
1
233
6
75
7
_ 1
1,005
Lb
Acres*
126.00
30.00
604.90
1.20
5,981.15
2.50
1,074.74
0.72
2,231.46
66.87
1,353.21
607.37
15.00
38.00
11,215.40
3.36
845.36
9,523.64
0.05
0.76
2 , 144 . 02
22.48
42.00
12.00
181.50
30.00
1,463.00
5.00
175.00
3,501,800
877,200
385.00
5.00
5,223.75
274,150
2,818.00
409.00
25,800
115,^57.16 31,991.30
* When the commodity listed is prefixed by Jf or U the amount listed
in the respective acreage column is not acreage but one of the
following, and is not tabulated in total acreage:
U = Miscellaneous Units P = Pounds
Source: California Department of Agriculture, op. cit. (1972).
157
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Table 25. USE OF CAPTAN IN CALIFORNIA IN 1973, BY CROPS,
APPLICATIONS, QUANTITIES, AND ACRES TREATED
p
p
p
p
p
p
Commodity
Alfalfa
Almond
Apple
Apricot
- Barley for seed
Beans, dry edible
Beans , green or forage
- Beans for seed
Berries
Cabbage
Carrot
Cauliflower
Celery
Cherries, sweet
Citrus
City agency
Corn, field
- Corn, field
Corn for seed
Corn for seed
Cotton
Cottonseed
County agricultural
commissioner
County or city parks
Cucumber or pickle
Flowers
Foliage
- Grain
Grapefruit
Grape
Lemon
Lettuce, head
Lettuce, leaf
Melons
Miscellaneous
Applications
1
139
9
125
1
1
1
14
1
3
1
1
22
9
5
63
1
5
8
6
9
4
92
5
1
8
411
3
70
5
2
1
Lb
0.64
47,554.07
184.12
22,874.32
4.83
0.24
9.00
1,220.12
90.00
2.08
70.00
1.04
580.00
579.12
2.06
1,684.28
216.89
0.01
103.43
3.04
1,141.64
17.78
5.50
6.42
29.00
592.13
52.84
94.81
510.25
52,005.38
25.44
1,484.32
28.00
360.00
0.12
Acres*
32.00
11,245.00
37.00
5,273.00
4,500
12.00
6.00
1,063,194
30.00
101.00
35.00
111.00
337.50
181.00
104.00
9,489.00
1,200
1,075.00
7,537
891.00
712.00
15.00
206.37
136.00
88,200
88.50
20,533.30
64.00
1,565.00
28.00
120.00
100
158
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Table 25. (Continued)
Commodity Applications Lb
Nectarine
Nonagricultural areas
Nursery stock
Onion, dry
P - Onion, dry
Orange
Ornamentals
Ornamental bedding plants
Other agencies
Peach
Pear
Peas for seed
P - Peas for seed
Pepper, bell
Pimento
Plum
Prune
Residential control
Rice
Saf flower
School district
Sorghum
Sorghum for seed
P - Sorghum for seed
Spinach
Squash, summer
State highway
Strawberry
Structural control
26
1
2
59
1
21
16
19
225
5
2
1
1
2
19
255
1
2
7
5
3
32
5
187
937.00
0.40
100.00
1,494.02
0.01
290.30
579.50
370.34
12,871.70
28,648.10
316.50
25,800.00
12.65
0.52
0.38
1,880.45
63,568.22
1,121.38
4.52
1.81
7.00
12.09
15.04
391.60
548.62
217.00
37.50
11,252.20
6.20
Acres*
298.00
1.00
52.00
852.25
130
325.00
304.50
86.23
6,938.25
101.00
172.00
36,000
100.00
150.00
440.50
15,246.50
201.00
140.00
675.00
772.00
228,030
529.50
96.00
5,122.75
159
-------
Table 25. (Continued)
p
p
Commodity
- Sudangrass for seed
Sugar beet
Tomato
University of California
Vector control
Walnut
- Wheat
Applications
2
3
92
2
1
Lb
1,596.60
13.43
8,019.07
2.05
0.12
318.04
0.03
Acres*
1,143,650
95.00
4,196.75
83.00
5,000
Total 2,024 291,967.31 89,406.50
* When the commodity listed is prefixed by P or U the amount listed
in the respective acreage column is not acreage but one of the
following, and is not tabulated in total acreage:
U = Miscellaneous Units P = Pounds
Source: California Department of Agriculture, op_. cit. (1972).
160
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PART III. MINIECONOMIC REVIEW
CONTENTS
Page
Introduction .......................... 163
Apples ............................. 165
Efficacy Against Pest Infestation .............. 164
Cost Effectiveness of Pest Control .............. 167
Peaches ............................ 167
Efficacy Against Pest Infestation .............. 167
Cost Effectiveness of Pest Control .............. 167
Strawberries .......................... 169
Efficacy Against Pest Infestation .............. 168
Cost Effectiveness of Pest Control .............. 169
Uses of Vegetables ....................... 170
Potatoes ........................... 170
Efficacy Against Pest Infestation ............. 170
Cost Effectiveness of Pest Control ............. 171
Soybeans ...........................
References ........................... 172
161
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This section contains a general assessment of the efficacy and
cost effectiveness of captan. Data on the production of captan in the
United States as well as an analysis of its use patterns at the regional
level and by major crop, were conducted as part of the Scientific Review
(Part II) of this report. For this reason, production and use data are
reported in the Production and Use subsection (p. 122) of the Scientific
Review.
Introduction.
The efficacy and cost effectiveness of a specific pesticide should
be measurable in terms of the increased yield or improved quality of a
treated crop which in turn results in a greater income or lower cost
than would be achieved if the pesticide had not been used. Thus, one
should be able to pick an isolated test plot of a selected crop, treat
it with a pesticide, and compare its yield with that of a nearby un-
treated test plot. The difference in yield should be the increase
due to the use of the pesticide. The increased income (i.e., the yield
multiplied by the selling price of the commodity) less the additional
costs (i.e., the pesticide, its application and the harvesting of the
increased yield) is the economic benefit due to the use of the pesti-
cide.
Unfortunately, this method has many limitations. The data derived
is incomplete and should be looked on with caution. Midwest Research
Institute's review of the literature and EPA registration files revealed
that experimental tests comparing crops treated with specific pesticides
to the same crop without treatment are conducted by many of the state
agricultural experimental stations. Only a few of these, however, have
attempted to measure increased yield and most of this effort has been
directed toward just a few crops such as cotton, potatoes, alfalfa and
selected fruits. Most other tests on crops measure the amount of reduc-
tion in pest levels which cannot be directly related to yield.
Even the test plot yield data are marginally reliable, since these
tests are conducted under actual field conditions that may never be
duplicated again and may not be representative of general field use.
Thus yield is affected by rainfall, fertilizer use, severe weather
conditions, soil type, region of the country, pesticide infestation
levels and the rate, frequency and method of pesticide application.
Because of these factors, yield tests at different locations and
in different years will show a wide variance ranging from a yield
decline to significant increases. For example, in a year of heavy
162
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pest infestation frequent pesticidal use can result in a high yield
increase because the crop from the untreated test plot is practically
destroyed. Conversely, in a year of light (or insignificant) infes-
tation, the yield increase will be slight (or undetectable).
The use of market price to estimate the value received by the
producer also has its limitations. If the use of the pesticide in-
creases the yield of a crop and the national production is increased,
then the market price should decline. According to J. C. Headley
and J. N. Lewis (1967),—' a 1% increase in quantity marketed has at
times resulted in a greater than 1% decrease in price. Thus the marginal
revenue from the increased yield would be a better measure of value
received.
A third limitation to the quantification of the economic costs
and benefits is the limited availability of data on the quantities
of the pesticide used by crop, disease or pest, the acres treated,
and the number of applications. In most cases the amount of captan
used on each crop or to treat each disease is not available.
As a result of these limitations an overall economic benefit by
crop or pest cannot be determined. This report presents a range of
the potential economic benefits derived from the use of captan to
control a specific disease on a specific crop. This economic benefit
or loss is measured in dollars per acre for the highest and lowest
yield increase developed from experimental tests conducted by the
pesticide producers and the state agricultural experimental stations.
The high and low yield increases are multiplied by the price of the
crop and reduced by the cost of the captan applied to generate the
range of economic benefits in dollars per acre.
In certain industrial, institutional, commercial, consumer and
governmental uses, economic benefits are difficult to assess by the
above methods. Because of large uses for aesthetic reasons along
with the absence of field test data no attempt was made to assign
an economic benefit to this area.
I/ Headley, J. C., and J. N. Lewis, The Pesticide Problem: An Economic
Approach to Public Policy, Resources for the Future, Inc., Washington,
D.C. (1967).
163
-------
Captan was first introduced as a fungicide in 1948 and has found
its largest use for treating fruits and vegetables to prevent scab
and rot. Not only does it control diseases without burning foliage
and fruit, it promotes greater carbohydrate production and storage
by plant tissues, resulting in heavier foliage growth, increased fruit
set and better fruit color and finish. Captan is available as a
variety of wettable powder and dust formulations.
Data on the efficacy and economic benefits due to the use of
captan have been reported for selected fruits and vegetables. These
include benefits from the control of scab and rot on apples, brown
rot and scabs on peaches, gray mold on strawberries, potato scab on
potatoes, and seed diseases of soybeans. These results are summarized
in the following paragraphs.
Apples
Efficacy Against Pest Infestation - Approximately 5,700,000 Ib of
captan were used in 1972 for fungicidal control of apple trees.
Captan is a good all-round fungicide for control of scab and rots;
it provides good finish and is often applied as a combination with
other fungicides and insecticides.
A review of available literature and the EPA registration files
has revealed numerous experiments which determined yields of apples
treated with captan. Unfortunately, most of these experiments compare
captan-treated apple trees with other chemicals. Most of these exper-
iments were conducted in the 1950 to 1954 period and often relate
the yield changes in bushels per tree. Others report the use of captan
in terms of pounds per hundred gallons of water but do not relate it
to the quantity applied to the tree.
A review of Fungicide and Nematocide Tests published by the
American Phytopathological Society revealed numerous tests conducted
on apple trees but most reported the results in terms of percent control
of fruit scab or percent fruit infection which is difficult to relate
to yield. However, many indicated that they used 3 to 5 gal. of
spray per tree. Since a 50% wettable powder formulation (SOW) is
recommended for apples in a mixture containing 2 Ib of this formulation
per 100 gal of water this would result in a use of 0.06 to 0.10 Ib/tree
or an average of 0.08 Ib of the formulation per tree (0.04 Ib active
ingredient (AI) per tree).
164
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Yields from tests varied from a low of 3.0 bushels per tree from
a summary of tests in Pennsylvania in 1952 to a high of 30.1 bushels
per tree from tests conducted on Baldwin apples in Medina, New York,
in 1954.
Since there were no tests which compared captan - treated trees with
untreated trees actual yield benefits are impossible to determine.
Test results, however, have shown the untreated trees most often will
have up to 100% scab or rot which would render the fruit worthless or
significantly reduce its value.
The yield of apples following application of captan and other fungi-
cides is illustrated in the following table:
Table 26. YIELD (BUSHELS/TREE) FROM CAPTAN (ORTHOCIDE SOW) SPRAYED
APPLE TREES
Test 1 - University of Maryland, Dr. Castillo Graham -
Apple Variety and Year
Golden Delicious Stayman York
Treatment 1951 1953 1951 1953 1952 1953 1954
Captan 7.0 7.0 12.0 13.7 15.0 9.5 4.7
Standard 4.0 4.0 4.0 5.2 8.0 5.0 2.3
Fungicides*
Test 2 - California Spray Chemical Company, Medina, N.Y. -
Baldwin variety in year
Treatment 1953 1954
Captan 20.0 30.1
Standard Fungicide** 15.0 23.6
Test 3 - University of Maine, Dr. M. T. Hilborn -
Mclntosh variety in year
Treatment 1952 1953 1954
Captan 17.66 18.72 26.51
Standard Fungicide** 14.80 16.74 15.32
*A combination of two commercial standard fungicides.
** A commercial standard fungicide.
165
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Table 26. (Continued)
Test 4 - R. D. Wessel, Medina, N.Y. -
Treatment
Baldwin variety in year
1953 1954
Captan
Standard Fungicide**
19.9
21.7
26.6
19.7
Test 5 - Rutgers University, Dr. R. H. Davies -
Variety
Treatment
Captan
Standard Fungicide**
Standard Fungicide**A+ Captan
Standard Fungicides*
Standard Fungicide**B+ Captan
Red Delicious
7.1
4.3
6.7
5.3
6.6
Stayman
11.1
4.5
9.2
6.3
5.9
Source: California Spray Chemical Company and Stauffer Chemical Company,
EPA Pesticide Petition No. 124 (undated).
Table 27. YIELD AND PROFITS FROM USING ORTHOCIDE 50W IN SELECTED STATES
Yield (bushels/tree)
State
Pennsylvania
Maryland
Maryland
Maryland
West Virginia
Pennsylvania
Pennsylvania
Pennsylvania
Maryland
Maryland
New York
New Jersey
Rhode Island
Pennsylvania
Average
Year
1953
1951
1951
1952
1952
1953
1952
1953
1952-53
1953
1953
1953
1952
1952
Orthocide SOW
22.0
12.0
7.0
15.0
14.5
10.5
4.6
4.0
4.7
9.5
20.0
4.0
4.7
3.0
9.0
Sulfur - Ferbam
1.7
8.0
3.0
7.0
3.5
1.7
2.3
1.1
2.4
4.5
5.0
2.75
2.1
1.3
3.1
Source: California Spray Chemical Company and Stauffer Chemical Company.
EPA Pesticide Petition No. 124 (undated;.
166
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Cost_Effectiveness of Pest Control - If the extreme of complete destruction
of the apple crop without the use of captan is assumed, then a range of
benefits can be determined. The average price received for apples in 1972
was $0.64/lb and there is an average of 40 Ib of apples in a bushel
(Agricultural Statistics 1973).I/ Prices for captan SOW range from $0.75
to $0.90/lb (McGlohon, 1974).I/ This would average $0.825/lb, equivalent
to $1.65/lb of active ingredient. At a use of 0.4 Ib Al/tree, the captan
would cost $0.66/tree.
With apples at $0.064/lb, a 40-lb bushel of apples would yield an
income of $2.56. At this price the additional income for the yield
range of 3.0 to 30.1 bushels per tree would vary from $7.68 to $77.06/
tree. Subtracting the captan cost of $0.66 would yield an economic
benefit range of $7.02 to $76.40/tree from the use of captan.
Peaches
Efficacy Against Pesticide Infestation - Captan is used on peach trees to
control brown rot. A review of available literature revealed one test
which related yields to captan use. W. J. French (1969)3/ conducted tests
at the University of Florida in 1968 to evaluate captan SOW against brown
rot and scab on peaches. Seven treatments of captan SOW were applied to
the trees. The captan was used at a rate of 3 gal/tree and was formulated
with water at 2 lb/100 gal. (1 Ib AI per 100 gal.)
At these rates the captan use would amount to 0.03 Ib AI per tree
for each spray and 0.21 Ib AI per tree for the season. A yield of 146 Ib/
tree was obtained for the treated trees whereas an untreated plot yielded
104 Ib of peaches. This resulted in an increase of 42 Ib of fruit from
the use of captan.
Cost Effectiveness of Pest Control - The price of peaches in 1972 averaged
$0.07/lb (Agricultural Statistics 1973). At a yield increase of 42 Ib/
tree this would produce an additional revenue of $2.94/tree. At a price
of captan of $1.65/lb of active ingredient (McGlohon, 1974) and a use of
0.21 Ib/tree captan costs per tree would be $0.35. Subtracting the captan
costs from the additional revenue would yield an economic benefit of $2.59/
tree for the use of captan to prevent brown rot and scab.
J7 United States Department of Agriculture, Agricultural Statistics 1973.
2] McGlohon, Norman E., Head Extension Plant Pathology Department,
University of Georgia, College of Agriculture, Athens, Georgia,
personal correspondence with David F. Hahlen (July 10, 1974).
3j French, W. J., Abstr. 78, "Peach," Fungicide and Nematocide Test
Results of 1969. the American Phytopathological Society (1969).
167
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Strawberries
Efficacy Against Pest Infestation - Captan is used to prevent gray mold
on strawberries. Normally it is applied at a rate of 4 to 6 Ib/acre for
the 50% wettable powder, and 40 Ib/acre for the 7.5% dust.
A review of available literature and EPA registration files has
produced experiments which relate yields to captan use. All of the EPA
data consisted of experiments conducted from 1952 to 1954. Recent data
is presented in the following tables:
Table 28. RESULTS OF CAPTAN APPLICATION ON STRAWBERRIES
Application rate
Captan
7.5% Dust
50% Powder
7.5% Dust
50% Powder
7.5% Dust
50% Powder
7.5% Dust
50% Powder
50% Powder
Ib/acre
50
6
50
6
50
6
50
6
6
No.
5
5
5
5
5
5
5
5
3
Ib Al/acre
18.75
15.0
18.75
15.0
18.75
15.0
18.75
15.0
9.0
Yield
(qt/acre)
3,119
3,261
7,152
5,487
4,732
5,216
4,992
5,592
15,400
Increase
qt/acre
1,582
1,724
2,797
1,132
2,205
2,689
1,776
2,376
5,800
Ib/acre
2,370
2,586
4,196
1,698
3,308
4,033
2,664
3,564
8,700
Source
a/
a/
a/
a/
a/
a/
a/
a/
b/
aj California Spray Chemical Company and Stauffer Chemical Company,
"Captan," Petition No. 124 (undated).
b_/ Baldwin, R. E., "Strawberries," Fungicide and Nematocide Test Results
of 1968, the American Phytopathological Society (1968).
The results of these tests show that increases in yield of straw-
berries ranged from a low of 1,698 Ib/acre with an application of 15.0
Ib Al/acre of captan, to a high of 8,700 Ib/acre with an application of
9.0 Ib Al/acre of captan.
The yield of strawberries following application of Orthocide (captan)
is illustrated in the following tests—' :
I/ California Spray Chemical Company and Stauffer Chemical Co., EPA
Pesticide Petition No. 124.
168
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Table 29. YIELD RESULTS (QUARTS/ACRE) AND PROFITS FOR FIVE APPLICATIONS
OF CAPTAN TO STRAWBERRY PLANTS
Test 1 - Gray mold control test, Haddenfield, New Jersey, 1953 -
Rate Gross receipts
Treatment Lb/Acre Qt/Acre at $.35/Qt
Captan 7.5 Dust 50 3,119 $1,091.65
Captan SOW 6 3,261 1,141.35
Standard Fungicides* - 2,186 765.10
Check 1,537 537.95
Test 2 - Gray mold control test, Haddenfield, New Jersey, 1954 -
Rate Gross receipts
Treatment
Lb/Acre Qt/Acre at $.35/Qt
Captan 7.5 Dust 50 7,152 $2,503.20
Captan SOW 6 5,487 1,920.65
Check 4.355 1,524.25
Test 3 - Gray mold control test, Moorestown, New Jersey -
Treatment
Captan 7.5 Dust
Captan SOW
Check.
Rate
Lb/Acre
50
6
Qt/Acre
4,732
5,216
2,527
Gross receipts
at $.35/Qt
$1,656.20
1,825.60
884.45
A combination of two commercial standard fungicides.
Cost Effectiveness of Pest Control - At a price of $1.65/lb AI for captan
SOW (McGlohon, 1974), the respective costs would be $24.75 and $14.85/acre.
The average price of strawberries in 1972 was $24.00/cwt (Agricul-
tural Statistics 1973). At this price, yields would generate an additional
income ranging from $407.52/acre to $2,088.00/acre. Subtracting the captan
cost would result in economic benefits ranging from $328.77 to $2,073.IS/
acre due to the use of captan to control gray mold.
169
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Uses on Vegetables
Although 400,000 Ib of captan were used in 1972 to treat .vegetable
crops its use is probably declining due to the development of improved
fungicides. Recent literature indicates that captan is not being evaluated
during fungicidal tests conducted by the various agricultural field
stations. McGlohon (1974) states that although captan has a label regis-
tration for vegetables in Georgia, there are other fungicides that are
more effective.
Potatoes -
Efficacy Against Pest Infestation - Captan has been used as a fungicide
for treatment of potato seeds. Cetas (1966)1.' has conducted yearly tests
at the Cornell University, Long Island Research Farm, to evaluate captan
and other fungicides for the control of potato scab (Rhizoctonia solani).
The results of these tests are shown in Table 30.
Table 30. RESULTS OF CAPTAN APPLICATION TO POTATO SEED PIECES
Captan
Content of
Formulation
(%)
7.5
7.5
7.5
7.5
15.0
7.5
15.0
7.5
15.0
Rate
Ib/cwt
seed
1
1
1
1
1
1
1
1
1
Ib AI/
acre
1.3
1.3
1.3
1.3
2.6
1.3
2.6
1.3
2.6
Yield
(cwt/acre)
351
247
283
277
303
383
406
301
315
Gain
(cwt/acre)
44
33
36
30
56
35
58
15
31
Source
a/
b/
£/
c/
c/
d/
d/
d/
d/
a/ Cetas (1966)!/
b/ Cetas, Robert C., "Potato," Fungicide and Nematocide Test Results of
1967, American Phytopathological Society, St. Paul, Minn, pp 120-
121 (1967). . PF- u
c/ Cetas, Robert C., "Potato," Fungicide and Nematocide Test Results of
1968, American Phytopathological Society, St. Paul, Minnpl7l~
(1968). '
Cetas, Robert C., "Potato," Fungicide and Nematocide Test Results of
1969, American Phytopathological Society, St. Paul, Minn. (1969).
d/
I/ Cetas, Robert C., "Potato," Fungicide and Nematocide Test Results of
1966. American Phytopathological Society, St. Paul, Minn. pp. 72-
73 (1966).
170
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The results of these tests show that yield increases range from 15
to 58 cwt/acre.
Cost Effectiveness of Pest Control - The price of potatoes averaged $2.55/
cwt in 1972 (Agricultural Statistics, 1973), At this price the additional
income at the above yields would vary from $38.25 to $147.90 per acre.
A 7.5% dust formulation of captan was used at a rate of 1.0 Ib/cwt
of seed potatoes. Approximately 17.2 cwt of seed potatoes are required
per acre of potatoes (Agricultural Statistics. 1973.) This would
require 17.2 Ib/acre of the formulation (1.3 Ib Al/acre).
The price of captan (7.5%) is about 15c/lb ($2.00/lb AI) (California
Spray-Chemical, 197417). Subtracting the captan cost from the additional
income at the respective application rates would result in economic
benefits ranging from $35.65 to $142.50 per acre for the use of captan
on potatoes.
Soybeans -
One test was reported in the 1967 issue of Fungicide and Nematocide
Test Results concerning the use of captan on soybean seedlings. A. Y.
Chambers (1967)—/ of the Tennessee Agricultural Experimental Station
found taht soybean yield increased from 33.3 bushels/acre to 37.0 bushels/
acre when the seed was treated with 3 oz of 50% captan per 100 Ib of seed.
He reported that 30 Ib of seed were required per acre. At this rate captan
(AI) use per acre would amount to 0.028 Ib. This increase would amount to
a yield increase of 3.7 bushels/acre. At a 1972 average price of $3.49/
bushel for soybeans (Agricultural Statistics, 1973) the additional income
would be $12.91/acre. At captan prices of $1.65/lb (AI) (McGlohon, 1974)
the cost of 0.028 Ib would be $0.05/acre when captan is used as a fungicide.
J7 California Spray-Chemical Corporation, Kansas City, Missouri, Personal
communication to Mr. David F. Hahlen (Midwest Research Institute,
Kansas City, Mo.) (July 15, 1974).
2J Chambers, A. Y., "Soybeans," Fungicide and Nematocide Test Results of
1968, American Phytopathological Society, St. Paul, Minn., p. 124
(1967).
171
-------
References
California Department of Agriculture, Pesticide use reports for 1970, 1971,
1972 and 1973.
California Spray-Chemical Corporation, Kansas City, Missouri, Personal commu-
mication to Mr. David F. Hahlen (Midwest Research Institute, Kansas City,
Mo.) (July 15, 1974).
California Spray Chemical Company and Stauffer Chemical Company, EPA Pesticide
Petition No. 124.
Cetas, Robert C., "Potato," Fungicide and Nematocide Test Results of 1966,
'American PhytopathologicaT. Society, St. Paul, Minn., pp. 72-73 (1966).
Cetas, Robert C., "Potato," Fungicide and Nematocide Test Results of 1967,
American Phytopathological Society, St. Paul, Minn., pp. 120-121 (1967).
Cetas, Robert C., "Potato," Fungicide and Nematocide Test Results of 1968,
American Phytopathological Society,"StT PauTT Minn.~, p. Ill (1968).
Cetas, Robert C., "Potato," Fungicide and Nematocide Test Results of 1969,
American Phytopathological Society, St. Paul, Minn. (1969).
Chambers, A. Y., "Soybeans," Fungicide and Nematocide Test Results of 1968,
American Phytopathological Society, St. Paul, Minn., p. 124 (1967).
Chevron Chemical Company, Orthocide Product Brochure, San Francisco,
California.
Frear, D. E. H., Pesticide Handbook-Entoma, 24th ed., College Science Publishers,
State College, Pa. (1972).
French, W. J., Abstr. 78, "Peach," Fungicide and Nematocide Test Results of
1969, the American Phytopathological Society (1969).
Headley, J. C., and J. N. Lewis, The Pesticide Problem: An Economic Approach
to Public Policy, Resources for the Future, Inc., Washington, D.C. (1967).
McGlohon, Norman E. (Head^Extension Plant Pathology Department, University
of Georgia, College of Agriculture, Athens, Georgia) Personal Correspondence
with David F. Hahlen (10 July 1974).
Midwest Research Institute/RvR Consultants, "Production, Distribution, Use
and Environmental Impact Potential of Selected Pesticides," (Draft) Council
on Environmental Quality Control, Contract No. EQC-311 (March 1974).
U.S. Bureau of the Census, U.S. Exports, Schedule B. Commodity by Country
Report FT 410.
172
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U.S. Department of Agriculture, Agricultural Statistics 1973.
Agency» EPA Compendium of Registered Pesticides.
and Nematnr-M«Q
Benzenoid chemicals and products' TC
U.S. Tariff Commission, Synthetic Organic Chemicals. U.S. Production and
Sales. 1972 TC Publication 681 (1973).
•d U.S. GOVERNMENT PRINTING OFFICE: 197S-
210-810/22
173
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