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Study Title

Publicly Releasable Summary of the Petition

for Establishment of a Tolerance 

for Captan in or on Ginseng 

EPA Registration Action References

IR-4 Tolerance Petition

PP# 4E8257

Author

Bert Volger, Ph.D.

Document Date

February 24, 2014

Prepared by

Captan Task Force

c/o Makhteshim-Agan of North America Inc.

3120 Highwoods Blvd, Suite 100

Raleigh, NC 27604

Submitted by

Interregional Research Project No.4

Rutgers, The State University of NJ

Center for Minor Crop Pest Management

500 College Road East, Suite 201 W

New Brunswick, NJ 08540
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Interregional Research Project Number 4 (IR-4)

EPA has received a pesticide petition (PP # 4E8257) from IR-4 Project Rutgers, 

The State University of New Jersey, 500 College Road East, Suite 201 W, Princeton, 

NJ 08540 proposing, pursuant to section 408(d) of the Federal Food, Drug, and 

Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR 180.103 by establishing a 

tolerance for residues of the fungicide, captan (N-trichloromethylthio-4-cyclohexene-1,2-

dicarboximide) in or on ginseng at 1.5 ppm. The Captan Task Force (CTF) represented 

by Makhteshim-Agan of North America Inc., 4515 Falls of Neuse Road, Raleigh, NC 

27609, and Arysta Life Science, 15401 Weston Parkway Suite 150, Cary, NC 27513, 

are basic registrants of captan. CTF prepared and summarized the following 

information in support of the pesticide petition for captan. EPA has determined that the 

petition contains data or information regarding the elements set forth in section 

408(d)(2) of the FFDCA. However, EPA has not fully evaluated the sufficiency of the 

submitted data at this time or whether the data support granting of the petition. 

Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

The residue chemistry data base for captan is complete.

1. Plant Metabolism 

The qualitative nature of the residue of captan in plants is adequately understood based 

on acceptable lettuce, and tomato metabolism studies. Captan is the major residue.

Minor residues identified in the plant metabolism studies included 1,2,3,6-

tetrahydrophthalimide (THPI), captan epoxide, and THPI epoxide.

Bis(trichloromethyl)disulfide, trans-3-hydroxy-1,2,6-trihydrophthalimide (3-OHTHPI), and 

trans-5-hydroxy-1,2,6-trihydrophthalimide (5-OH-THPI) may also be present at very low 

levels. Based on the results observed in the metabolism studies, the first step in the 

metabolism of captan is the cleavage of captan’s N-S bond to form 

tetrahydrophthalimide (THPI), and a derivative of the trichloromethylthio side chain

secondary residues, such as phthalimide and phthalic acid, which are not expected to 

be of toxicological concern. Because captan is extensively metabolized to THPI in 

animal tissues, and THPI comprises less than 10% of the total captan residue for 

plants, the Agency concluded that the residue of concern, which should be regulated in 

plants, is the parent compound, captan, only. 

2. Analytical Method

An adequate analytical method, gas chromatography/electron capture detector 

(GC/ECD), is available for enforcement of tolerance residues of captan per se in or on 

plant commodities, and is listed as Method I, in PAM, Vol. II Zeneca Method No. 166 for 

quantifying THPI in meat and milk has been validated as the preferred enforcement 
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method. The limit of detection (LOD) is 0.02 mg/kg (ppm) and the lowest level of 

method validation (LLMV) is 0.05 mg/kg (ppm). Captan is completely recovered using 

FDA Multiresidue Protocols D (Luke Method; 232.4) and E Section 211.1 for oily 

matrices and partially recovered using FDA Multiresidue Protocol E Section 212.1 for 

non-oily matrices. THPI is completely recovered using FDA Multiresidue Protocol D.

3. Magnitude of Residues

Four field residue trials were conducted covering the major ginseng growing 

areas, NAFTA Region 5 (2 trials in Wisconsin, 1 trial in Ontario), and NAFTA Region 11 

(1 trial in British Columbia) during 2005 and 2006. Captan was applied eight times, 

following a 6 to 8 day spray interval, using a maximum application rate of 3.0 lbs active 

ingredient per acre or 24 lbs per season, with the last application 12 to 15 days before 

harvest. The ginseng samples from three of the four trials had residues at or below the 

LLMV (≤ 0.05 ppm), but in the fourth trial the samples had residues as high as 1.0 ppm 

(multiple analyses were conducted to confirm the residues). CTF concludes that the 

generated data set is in full support of the proposed tolerance of 2.0 ppm.

B. Toxicological Profile

1. Acute Toxicity

i. In general, captan has been shown to be of low acute toxicity: The acute oral

LD50 in rats is 9,000 mg/kg, and the acute dermal LD50 in rats is greater than 2,000 

mg/kg. The acute inhalation LC50 (4-hour) was 0.72 mg/l for male rats, and 0.87 mg/l for 

females. Captan is very irritating to the eyes of rabbits, not irritating to the skin, but 

considered a dermal sensitizer as shown in guinea pigs. Based on these results, 

captan is classified in Toxicity Category IV for acute oral and dermal sensitization, in 

Category III for acute dermal and inhalation toxicity, and in Category I for eye irritation.

ii. The Agency selected the developmental NOAEL of 10 mg/kg/day from the 

prenatal developmental toxicity study in rabbits for deriving the acute Reference Dose

(aRfD = 0.1 mg/kg/day). The Reference Dose (RfD) equals the Population Adjusted

Dose (PAD).

2. Genotoxicity

The mutagenic potential of captan was investigated in several in vivo and in vitro 

studies. Captan is neither mutagenic nor genotoxic in mammals (in vivo assays). In 

some of the in vitro studies, mutagenic events were observed, such as chromosome 

aberrations, sister chromatid exchanges and single strand DNA breaks in mammalian 

cells. Overall, the data support the contention that captan is an in vitro mutagen and 

clastogen that is not active in the whole animal because it reacts with thiols or proteins 

that rapidly deactivate captan or its reactive breakdown product (thiophosgene). Captan

does not present a genotoxic risk based on the fact that captan or thiophosgene 
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degrade with a half-life of less than one second in blood. This fast detoxification 

effectively eliminates systemic exposure to captan or thiophosgene. The Agency 

concluded in its 2004 Cancer Assessment Review Committee (CARC) meeting that 

captan is not genotoxic in vivo, and the weight-of-the-evidence supports a nongenotoxic 

mode of action for captan. Therefore, future quantification of cancer risk will be through 

a non-linear (RfD) approach. 

3. Reproductive and Developmental Toxicity

i. In a three-generation reproduction study rats were treated with captan at 25, 

100, 250, and 500 mg/kg/day. Non-reproductive parental toxicity was seen at 100 

mg/kg/day and above in the absence of reproductive effects. Pup weights were lower 

by 7% compared to controls at 25 mg/kg/day. A subsequent one-generation study 

conducted at 0.6, 12.5, and 25 mg/kg/day showed no effect on pup weights at 25 

mg/kg/day.

ii. Teratology studies were conducted in the rat, hamster and rabbit. In rats, 

captan was administered at 0, 18, 90, and 450 mg/kg/day exhibiting decreased 

maternal weight gain and decreased food consumption at the high dose. No effects on 

post-implantation loss or fetal survival were observed. Fetal body weight was reduced

and the incidence of "small" fetuses was increased at the high dose. There were no 

increases in incidences of treatment-related malformations. The incidence of minor 

skeletal variations, including the presence of a fourteenth (lumbar) rib, incomplete 

fusion of vertebral hemicentra fusion, and reduced ossification of the pubes was 

increased at 450 mg/kg per day. The NOAELs for maternal and developmental toxicity 

in this study were 18 and 90 mg/kg/day, respectively.

In the prenatal developmental toxicity study in hamsters, delayed ossification and postimplantation loss occurred at 400 mg/kg/day (the developmental LOAEL), while in 

dams, decreased body weight and mortality were observed at a LOAEL of 200 

mg/kg/day. The developmental NOAELs for maternal and developmental toxicity in the 

prenatal developmental hamster study were 50 and 200 mg/kg/day, respectively.

Studies in hamsters and rabbits showed that developmental and reproductive toxicity 

occurs only at or above doses that cause toxicity to parental animals.

In establishing an acute Population Adjusted Dose (aPAD), the Agency determined to 

use 0.1 mg/kg/day, based on a NOAEL of 10 mg/kg/day from the cited developmental 

study in rabbits. In this study, post-implantation loss, reduced mean fetal weight, and 

increased skeletal defects in fetuses were observed at 30 mg/kg/day. This dose reflects 

application to the NOAEL of an uncertainty factor of 100X to account for interspecies 

extrapolation and intraspecies variability.

4. Subchronic Toxicity

Rats, mice, and dogs all show the same toxicological response. These studies 
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confirm the irritant properties of captan, the effects of irritation to the duodenum, and 

the reversibility of these effects upon cessation of treatment. Observations in rats also 

include hyperkeratosis and acanthosis of the esophagus and stomach, and in the 

mouse it includes reduced weight gain and depressed food intake at high doses. 

Wistar rats treated for 4 weeks with captan at 0, 2,000, 4,000, 8,000, or 12,000 

ppm were observed to have a dose-related decrease in body weight gain and food 

intake. At the top two doses, there were increases in basophilia of hepatocytes in the 

periportal area of the liver accompanied by increases in relative liver weight. A similar 

finding was observed in the females at the next lower dose (4,000 ppm). The relative 

organ to body kidney weights were statistically increased at all doses.

Male CD-I mice (four or five per group) treated with 3,000 ppm for 1, 3, 7, 14, or 

28 days showed shortened duodenal villi due to damage by captan. This effect was 

observable in the crypts within 3 days of treatment initiation. Immature cells were 

observed at the villi tips from day 7 onward, indicating a higher turnover of cells. There 

was some focal gastritis and parakeratosis noted in one mouse. When captan is fed to 

mice at 6,000 ppm for 28-90 days, villus atrophy occurs, together with a crypt 

hypertrophy and crypt cell hyperplasia.

CD-l mice administered captan for 56 days as 0, 400, 800, 3,000, or 6,000 ppm 

were evaluated for proliferative changes in the duodenum. An assessment of the 

duodenum was made using histopathology and a bromodeoxyuridine-labeling index to 

measure crypt cell proliferation. Captan induced hyperplasia of the crypt cells, an 

increase in the crypt cell labeling index, and an increase in the number of cells in the

crypt cell population. At 3,000 ppm, the villus-to-crypt height ratio decreased from 5.4 in 

males and 5.9 in females to 1.4 and 2.6, respectively. These observed changes are 

consistent with an irritant action of captan on the duodenum. The no observed effect 

limit (NOEL) for duodenal hyperplasia is 400 ppm.

Beagles, two per sex per treatment group, were administered captan at 0, 30, 

100, 300, 600, or 1,000 mg/kg/day for 4 weeks. The results included treatment-related 

emesis and a dose-related decrease in food intake and body weight gain. There was an 

increase in relative liver weight in males at 600 and 1,000 mg/kg/day and relative kidney

weight in females at 1,000 mg/kg/day. Some fatty changes were seen in the kidney and 

liver of one male at 1,000 mg/kg/day.

5. Chronic Toxicity

i. Chronic toxicity and oncogenicity was evaluated in the rat, mouse and dog. 

Based on recent chronic toxicity and carcinogenicity studies performed in rats, the 

NOAEL for systemic effects was 25 mg/kg/day. At the LOAEL of 100 mg/kg/day, males 

displayed hepatocellular hypertrophy; increased relative organ weight for kidneys 

(males and females); increased relative organ weight for heart, brain, liver and 

thyroid/parathyroid (males); and decreased body weight. At the same dosage, females 
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displayed increased relative organ weight for kidneys, and decreased body weight. 

There was a significant increasing trend in males for the combined adenomas and 

carcinomas of the kidney in male rats. There was no increased incidence of renal 

cortical/tubular cell neoplasia in females.

In mice, prolonged ingestion of high dose levels of captan causes an increased 

incidence of tumors (adenomas and adenocarcinomas) in the small intestine (primarily 

the proximal portion of the duodenum) in both sexes of mice. Tumors are observed in 

females only at dietary levels of at least 800 ppm (120 mg/kg/day) and in males at 

levels of at least 6,000 ppm (900 mg/kg/day) that exceed the maximum tolerated dose. 

In all studies, the tumorigenic response exhibits a clear dose threshold below which no 

effect occurs. A careful evaluation of the results of the rat bioassays provides no 

evidence that captan is associated with increased incidences of either renal tumors in 

males or of uterine sarcomas in females.

Dogs were treated with captan at 0, 12.5, 60, and 300 mg/kg/day for 1 year. Only 

the high-dose animals differed from control in increased incidence of emesis and soft 

stool, increased relative liver weight, and decreased total serum protein and albumin,

resulting in a NOAEL of 60 mg/kg/day. 

The Agency’s CARC agreed in 2004 that the results of the rat bioassays provide 

no evidence that captan is associated with kidney tumors in male rats or uterine tumors 

in female rats, and, therefore, these tumors do not add to the weight-of-evidence 

considerations for the carcinogenicity of captan. 

ii. A three-generation reproduction study in rats is the basis for the chronic RfD. 

The NOAEL in the study was 12.5 mg/kg/day based on decreased mean litter weights 

at the next higher dose level of 25 mg/kg/day. For the chronic dietary exposure 

assessment the chronic PAD of 0.13 mg/kg/day is obtained by application of an 

uncertainty factor of 100 for interspecies and intraspecies variability.

iii. The Agency originally classified captan as a “B2 - probable human 

carcinogen” using the linear (Q1*) methodology based on an increased incidence of 

intestinal tumors in mice, using a (body weight) scaling factor. In September 2004, the 

Agency, in accordance with the new Carcinogen Risk Assessment Guidelines, 

determined that captan acts through a non-genotoxic threshold mode of action, and 

considers captan to be a potential carcinogen at prolonged high doses that cause 

cytotoxicity and regenerative cell hyperplasia. However, these high doses of captan are 

many orders of magnitude above those likely to be consumed in the diet, or 

encountered by individuals in occupational or residential settings. Therefore, captan is 

not likely to be a human carcinogen nor pose cancer risks of concern when used in 

accordance with approved product labels. Since the CARC determined that there is a 

plausible mode of action, captan should be regulated based on a non-linear risk 

assessment, and a non-linear point of departure (RfD) will be selected since there are 

sufficient data to ascertain the mode of action for the tumor response. This decision 
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was based on the following weight-of-evidence considerations: (i) The occurrence of 

adenomas and adenocarcinomas in the small intestine of male and female mice; (ii) 

Captan is not likely to be genotoxic in vivo; (iii) The weight-of-evidence suggests that 

captan induces small intestine tumors by a nongenotoxic mode of action involving 

cytotoxicity and regenerative cell hyperplasia that exhibits a clear dose threshold.

6. Animal Metabolism

The metabolism of captan in animals is adequately understood. When ingested, 

captan is relatively stable in the acidic environment of the stomach. It is hydrolyzed 

more rapidly in the neutral environment of the duodenum to THPI and thiophosgene. 

Captan can also react chemically with sulfhydryl-containing compounds present in the 

gut or in the gut epithelial cells. The cytoplasm of most animal tissues contains high 

concentrations of GSH S-transferases that will increase the rate of reaction between 

thiophosgene and GSH. 

In the unlikely event that captan survives long enough to enter the systemic 

circulation, it will be broken down very rapidly by thiols in the blood to THPI and 

thiophosgene. The Agency concluded that thiophosgene is so labile that residues after 

oral ingestion of captan are not quantifiable. Thiophosgene, in fact, is broken down with 

a half-life of approximately 0.6 seconds.

7. Metabolite Toxicology

 

The Agency concluded that there are no captan metabolites of toxicological 

concern and therefore, the tolerance expression for raw and processed agricultural 

commodities should remain as captan per se. Because captan is extensively 

metabolized to THPI in animal tissues, the Agency determined that the tolerance 

expression for animal commodities should include THPI as well as captan. For drinking 

water assessment the major captan soil degradate, THPI, is considered besides the 

parent, captan. 

8. Endocrine Disruption

 

No special studies investigating potential estrogenic or other endocrine effects of 

captan have been conducted. However, no evidence of such effects is reported in the 

standard battery of required toxicology studies, which have been completed and found 

acceptable. Based on these observations, there is no evidence to suggest that captan 

has an adverse effect on the endocrine system. 

C. Aggregate Exposure

1. Dietary Exposure 

Current tolerances for residues of captan have been established in or on 
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almonds; almond, hulls; animal feed, nongrass (Group 18); apple; apricot; blueberry; 

caneberry (Subgroup 13A), cherry, sweet; cherry, tart; cotton, undelinted seed; dill, 

seed; flax, seed; grape; grain, cereal, forage, fodder and straw (Group 16); grain, cereal 

(Group 15); grass, forgae; grass, hay; nectarine, okra, peach, peanut, peanut, hay; 

pear, plum, prune,fresh; rapeseed, forage; rapeseed, seed; safflower, seed; sesame, 

seed; strawberry; sunflower, seed; vegetable, brassica leafy (Group 5); vegetable, bulb 

(Group 3); vegetable, cucurbit (Group 9); vegetable, foliage of legume (Group 7); 

vegetable, fruiting (Group 8); vegetable, leafy, except brassica (Group 4) , vegetable, 

leaves of root and tuber, (Group 2), vegetable, legume (Group 6); vegetable, root and 

tuber (Group 1), and livestock commodities and milk (40 CFR 180.103). In addition to 

the existing tolerances, this Notice of Filing includes exposure assessments for 

potential residues of captan in or on ginseng. 

i. Food

a. Acute Dietary Exposure. For the purposes of assessing acute dietary risk, 

CTF has used the results of the Agency’s completed risk assessment from November 

2004 (Amendment to the 1999 Captan RED). The Agency selected for the acute 

toxicological endpoint the developmental NOAEL of 10 mg/kg/day from the prenatal 

developmental toxicity study in rabbits determining acute dietary risks to the general 

population including infants and children. The Agency conducted an acute probabilistic 

dietary (food) exposure analysis using the Dietary Exposure Evaluation Model 

(DEEMTM). Residues in food items were estimated from residue field trials, USDA/PDP 

and FDA pesticide monitoring data, and reduction/concentration factors when available.

The acute analysis evaluated the dietary exposure based on individual consumption 

data from USDA's 1989-1992 Nationwide Continuing Surveys for Food Intake by 

Individuals (CSFII). For the acute assessment, exposure is compared to the acute 

population adjusted dose (aPAD). The aPAD refers to the acute RfD of 0.1 mg/kg/day, 

which has been adjusted to take into account the FQPA safety factor. For captan, the 

acute RfD equals the aPAD, since the FQPA safety factor is 1. The calculated dietary 

exposure for the most exposed subgroup, females 13 - 50 years, at the 99.9th percentile 

is 36% of the aPAD. In view of the negligible residue situation by adding the minor use 

crop, ginseng, as a food-crop to the label, CTF concludes that the acute probabilistic 

dietary risk for captan is below the Agency’s level of concern.

b. Chronic Dietary Exposure. To assess chronic dietary exposure, a DEEMTM

chronic exposure analysis was performed using anticipated residues and percent of 

crop treated information to estimate the anticipated residue contribution (ARC) for the 

general U.S. population and 22 subgroups. It should be noted that residues of captan 

plus the metabolite, THPI, were included in the ARC for acute and chronic exposure in 

meat and milk. For this assessment, exposure was compared to the chronic population 

adjusted dose (cPAD) of 0.013 mg/kg/day based on the NOAEL of 12.5 mg/kg/day from 

the three-generation reproduction study in rats, and based on an uncertainty factor of 

100 and a FQPA safety factor of 1. Considering these assumptions the chronic dietary 

exposure estimate for the overall U.S. population is 0.5% or 0.000664 mg/kg/day of the 
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cPAD, and for infants less than 1 year old, the most exposed population subgroup, it is

1.3% or 0.001629 mg/kg/day of the cPAD. Based on the existing uses and the 

insignificant residue contribution from the proposed use on ginseng as a food-crop, it 

has been demonstrated that the chronic dietary risk from exposure to captan does not 

exceed the Agency's level of concern, since all population subgroups having exposure 

values below 2% of the cPAD. Therefore, CTF concludes that there is reasonable 

certainty of no harm for the additional, new use of captan on ginseng.

c. Cancer. Based on the Agency’s 2004 cancer reassessment, it can be 

concluded that captan acts through a non-genotoxic threshold mode of action, and 

captan is not likely a human carcinogen nor poses cancer risks of concern when used in 

accordance with approved product labels. Therefore, a quantitative cancer risk 

assessment has not been conducted.

ii. Drinking Water

Since drinking water monitoring data for captan were not available, Drinking 

Water Levels Of Comparison (DWLOCs) were calculated and compared to Estimated 

Drinking Water Concentrations (EDWCs) that were generated by the PRZM-EXAMS 

and SCI-GROW models for captan residues in surface water and ground water, 

respectively. Based on the model predictions and the environmental fate characteristics 

of THPI, the Agency predicts how much captan will reach as THPI in drinking water 

from the current use pattern. 

a. Acute Exposure. The acute DWLOC of 1,920 μg/L is a far greater value than 

the conservative numbers that were estimated for the acute drinking water exposure 

through Tier 1 modeling (668 μg/L for surface water and 3.40 μg/L for ground water). 

Therefore, CTF concludes acute drinking water exposure added to the acute dietary 

exposure does not result in a risk concern.

 

b. Chronic Exposure. Chronic DWLOCs were calculated using the same inputs 

and similar equations as for the acute DWLOCs. Regarding the chronic aggregate 

exposures to captan residues, the calculated EDWCs were 10.8 and 3.4 μg/L for surface 

water and ground water, respectively, while the chronic DWLOC for the US population 

was 4,550 μg/L, and for infants (less than 1 year old) it was 1,300 μg/L. Therefore, the 

EDWCs for captan residues of concern in ground and surface water did not exceed the 

Agency’s calculated DWLOC values. The proposed captan use on ginseng has an 

annual maximum application rate of 24 lbs a.i./A, which is far less than the total annual 

application rate for peaches (32 lbs a.i./A), which was considered in this assessment. 

Therefore, adding ginseng to the label would not result in any additional risk from the 

consumption of captan residues in drinking water.

2. Non-Dietary Exposure
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Occupational handler exposure was assessed in the 1999 RED using PHED as 

surrogate exposure data, and then re-evaluated in 2004 (Amendment to the 1999 

Captan RED) in support of using captan on various agricultural crops and nonagricultural crops; including seed treatment and residential use sites which may include 

ornamentals, fruit trees, and strawberries.

The recent occupational handler exposure assessments indicated that most 

short- and intermediate-term risks to handlers using captan were above 100, the level 

of concern, with Margins of Exposure (MOEs) ranging from 240 to 43,000 for multiple 

activities. MOEs for mixer/loader/applicators and flaggers ranged from 840 to 270,000. 

A MOE of 2,400 was calculated for on-farm seed planters. Also residential exposure 

from the use of captan around the home did not exceed the level of concern when 

aggregated with food and drinking water.

No chronic exposure scenarios are expected from residential uses of captan.

The Agency’s aggregate residential exposure assessment (Amendment to the 1999 

Captan RED - November 2004) resulted in acceptable margins of exposure (MOEs

>100) for all population subgroups and scenarios based on conservative screeninglevel assumptions. Therefore, CTF concludes that captan does not pose a risk due to 

short- and intermediate-term non-dietary aggregate exposure. 

D. Cumulative Effects

FQPA requires the Agency to consider the cumulative exposure to pesticides 

operating by a common mechanism of toxicity. Adequate policy permitting the 

estimation of cumulative exposure and effects is currently under development but is not 

yet complete. Although folpet and captan share the common metabolite thiophosgene, 

its role in folpet’s and captan’s toxicity has not been determined because thiophosgene 

is transient and not easily measurable. At such time as policy defining how to conduct a 

cumulative assessment has been finalized, the risk assessments will be revisited to 

determine whether captan shares a common mechanism of toxicity with any other 

substances, such as folpet, and whether a cumulative risk assessment is warranted.

Thus only the potential risks of captan have been considered in this assessment of its 

aggregate exposure.

E. Safety Determination

1. U.S. Population

Using the conservative exposure assessment described above, the estimated 

chronic aggregate exposure from food and water to the U.S. Population is 0.000664 

mg/kg/day, equal to 0.5% of the cPAD. In addition, the chronic exposure estimates for

the most exposed subgroup, infants less than 1 year old, is 0.001629 mg/kg/day,

utilizing 1.3% of the cPAD. Concerning the acute aggregate exposure the only 

population of concern is females 13 to 50 years old, utilizing 36% of the aPAD at the 
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99.9th percentile. As described before, the calculations for the aggregate short-term risk 

assessments, which provide estimates resulting from residential exposures of 1 to 7 

days duration, plus food and water exposures, do not exceed the Agency’s level of 

concern. No cancer aggregate risk assessment was conducted because the Agency’s 

2004 cancer reassessment concluded that captan acts through a non-genotoxic 

threshold mode of action, and captan should be regulated based on a non-linear risk 

assessment. In view of these assessments, CTF concludes that there is reasonable 

certainty that no harm will result from the proposed use of captan.

2. Infants and Children

Section 408 of FFDCA provides that EPA may apply an additional safety factor 

for infants and children to account for prenatal and postnatal toxicity and the 

completeness and adequacy of the toxicity and exposure data bases, the nature and 

severity of the effects observed in pre- and post-natal studies, and other information 

such as epidemiological data. The toxicology database for captan is complete including 

acceptable prenatal developmental toxicity studies in hamsters, rats and rabbits, and 

two reproduction studies in rats that have been used to assess the potential for 

increased sensitivity of infants and children. The data provided no quantitative or 

qualitative evidence of increased susceptibility of rats, rabbits or hamsters to in utero 

and/or postnatal exposure to captan. The Agency has determined, based on a weightof-the-evidence review of the available data, a developmental neurotoxicity study is not 

required for captan. The Agency has determined that the 10X safety factor for 

enhanced sensitivity to infants and children (as required by FQPA) for captan should be 

removed (reduced to 1X). As previously stated, aggregate exposure assessments 

utilize less than 36% of the aPAD, and less than 1.3% of the cPAD for either the entire 

U.S. Population or any of the population subgroups including infants and children. 

Therefore, CTF concludes that there is reasonable certainty that no harm will result to 

infants and children from aggregate exposure to captan residues from the proposed 

use.

F. International Residue Limits

There are no Canadian, Mexican, or Codex Maximum Residue Limits (MRLs) 

established for captan in or on ginseng. Therefore, international harmonization is not an 

issue for captan residues in or on the plant commodity, ginseng, at this time.