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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS 

PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: 

The Tea Association of the USA. PP# 

EPA has received a pesticide petition PP#_ from The Tea Association of the U.S.A., Inc., 

362 5th Avenue, Suite 801, New York, New York 10001, proposing, pursuant to section 408(d) 

of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 

180.434. 

1. by establishing tolerance for residue of Propiconazole, 1-[[2-(2,4-dichlorophenyl)-4-

propyl-1,3-dioxolan-2-yl] methyl]-lH-1,2,4-triazole in or on the raw agricultural 

commodity [Tea] at 4.0 parts per million (ppm). 

EPA has determined that the petition contains data or information regarding the elements set 

forth in section 408 (d)(2) of the FDDCA; however, EPA has not fully evaluated the sufficiency of 

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

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

A. Residue Chemistry. Trials to measure the magnitude of residues of propiconazole in tea 

were conducted in India and Sri Lanka to support the requested tolerance of propiconazo1e '" 

tea. These residue trials satisfy the requested tolerance on tea. 

1. Plant metabolism. The metabolism of propiconazole as well as the nature of the 

residues is adequately understood for purposes of the tolerances. Plant metabolism has 'leer 

evaluated in five diverse crops, wheat, grapes, celery, peanuts and carrots which should serve 

to define the similar metabolism of propiconazole in a wide range of crops. The plant 

metabolism pathway for propiconazole is well understood. Parent metabolite CGA-64250 is 
the major compound found in crops. Comparison of the metabolism of propiconazole in 

different plant species shows that the differences between the respective metabolic pathways 

to be quantitative in nature. 

2. Analytical method. Propiconazole parent has been reported to be detected by 

numerous multi-residue methods used in compliance and enforcement. US FDA Pesticide 

Analytical Method (PAM) 1 also indicates the ability to determine residues of propiconazole 

parent in a wide range of plant products. Consequently, US Government compliance and 

enforcement methods are available to support the proposed import tolerance and residue 

definition. 

3. Magnitude of residues .. Residue studies were performed in India and Sri Lanka to 

support the setting of a Codex CXL. These studies have been submitted under OPPTS 

860.1500 to support the requested import tolerance for propiconazole in/on tea. The 

maximum residue of propiconazole on tea was 1.8 ppm. These residue trials satisfy the 

proposed tolerance for tea of 4.0 ppm for parent propiconazole. 

8. Toxicological Profile 

1. Acute toxicity. Propiconazole exhibits low toxicity. Data indicated the following: a 

rat acute oral LD50 of 1,517 milligrams/kilograms (mg/kg); a rabbit acute dermal LD50 >6,000 

mg/kg; a rat inhalation LC50 >5.8 mg/liter air; minimal skin and slight eye irritation; and no 

sensitization. 

2. Genotoxicity. Propiconazole exhibits no mutagenic potential based on the following 

data: In vitro gene mutation test (Ames assay, rat hepatocyte DNA repair test, (human 

fibroblast DNA repair test), In vitro chromosome test, (human lymphocyte cytogenetic test), ~n 

vivo mutagenicity test, (Chinese hamster bone marrow cell nucleus anomaly test, Chinese 

hamster bone marrow cell micronucleus test, mouse dominant lethal test), and other 

mutagenicity test (BALB/3T3 cell transformation assay). 

3. Reproductive and developmental toxicity. In an oral teratology study in the rabbit, a 

maternal no observed adverse effect level (NOAH) of 30 mg/kg was based on reduced fo:d 

intake but without any fetotoxicity even at the top dose of 180 mg/kg. In an oral teratology 
study in the rabbit, a maternal NOAEL of 100 mg/kg was based on reductions in body weight 

gain and food consumption and a fetal NOAEL of 250 mg/kg was based on increased skeletal 

variations at 400 mg/kg. In an oral teratology study in the rat, a maternal and fetal NOAEL of 

100 mg/kg was based on decreased survival, body weight gain, and food consumption in the 

dams and delayed ossification in the fetuses at 300 mg/kg. In a second teratology study in the 

rat, a maternal and fetal NOAEL of 30 mg/kg was based on reductions in body weight gain and 

food consumption in the dams and delayed development in the fetuses at 90 and 360/300 

mg/kg. A supplemental teratology study in the rat involving eight times as many animals per 

group as usually required showed no teratogenic potential for the compound. A 2-generation 

reproduction study in the rat showed excessive toxicity at 5,000 ppm without any teratogenic 

effects. A 2-generation reproduction study in the rat showed no effects on reproductive or 

fetal parameters at any dose level. Postnatal growth and survival were affected at the top 

dose of 2,500 ppm, and parental toxicity was also evident. The NOAEL for development 

toxicity is 500 ppm. 

4. Subchronic toxicity. In a 21-day dermal study in the rabbit, a NOAEL of 200 mg/kg 

was based on clinical signs of systemic toxicity. In a 28-day oral toxicity study in the rat, a 

NOAEL of 50 mg/kg was based on increased liver weight. In a subchronic feeding study in the 

mouse, a NOAEL of 20 ppm (3 mg/kg) was based on liver pathologic changes. In a 13 week 

feeding study in the male mouse, a NOAEL of 20 ppm (3 mg/kg) was based on liver pathologic 

changes. In a 90 day feeding study in rats, the NOAEL was 240 ppm (24 mg/kg) based on a 

reduction in body weight gain. In a 90 day feeding study in dogs, the NOAEL was 250 ppm 

(6.25 mg/kg) based on reduced food intake and stomach histologic changes.] 

5. Chronic toxicity. In a 12-month feeding study in the dog, a NOAEL of 50 ppm (1.25 

mg/kg) was based on stomach histologic changes. In a 24 month oncogenicity feeding study in 

the mouse, the NOAEL was 100 ppm (15 mg/kg). The MTD was exceeded at 2,500 ppm in 

males based on decreased survival and body weight. Increased incidence of liver tumor was 

seen in these males but no evidence of carcinogenicity was seen at the next lower dose of 500 

ppm in either sex. In a 24 month chronic feeding/oncogenicity study in the rat, a NOAEL o~ 

100 ppm (5 mg/kg) was based on body weight and blood chemistry. The MTD was 2,500 ppl\1 

based on reduction in body weight gain and no evidence of oncogenicity was seen. Based or. 

the available chronic toxicity data, the Reference dose (RfD) for propiconazole is believed tc 

be 0.0125 mg/kg/day. This RfD is based on a 1 year feeding study in dogs with a NOAEL cf 

1.25 mg/kg/day (50 ppm) and an uncertainly factor of 100. No additional modifying factor for 

the nature of effects was judged to be necessary as stomach mucous hyperemia was the 'l'lost 

sensitive indicator of toxicity in that study. 
Using the Guidelines for Carcinogenic Risk Assessment published on September 24, 1986 {51 

FR 33992), the USEPA has classified propiconazole in group C for carcinogenicity (evidence of 

possible carcinogenicity for humans). The compound was tested in 24 month studies with 

both rats and mice. The only evidence of carcinogenicity was an increase in liver tumor 

incidence in male mice at a dose level that exceeded the maximum tolerated dose (MTD). 

Dosage levels in the rat study were appropriate for identifying a cancer risk. The Cancer Peer 

Review Committee recommended the RfD approach for quantitation of human risk. 

Therefore, the RfD is deemed protective of all chronic human health effects, including cancer.] 

6. Animal metabolism. Metabolism in animals is similar to plant metabolism. In animals both 

the rat and the goat rapidly metabolize and excrete propiconazole. Neither animal retains 

significant amounts of propiconazole or its metabolites in tissues. Significant quantities of 

parent or metabolites do not appear in goat's milk. Similar metabolites are produced by both 

species, and unconjugated (phase I) metabolites are similar in plants and animals. 

The metabolism profile supports the use of an analytical enforcement method that accounts 

for combined residues of propiconazole and its metabolites that contain the 2,4-

dichlorobenzoic acid (DCBA) moiety. 

7. Metabolite toxicology. There are no metabolites of concerned based on a 

differential metabolism between plants and animals. 

8. Endocrine disruption. Developmental toxicity studies in rats and rabbits and 

reproduction studies in rats gave no indication that propiconazole might have any effects on 

endocrine function related to development and reproduction. The sub-chronic and chronic 

studies also showed no evidence of a long- term effect related to the endocrine system. 

Further, due to the moderate rate of degradation of the product, there is no risk that 

propiconazole may accumulate in the environment. In animals, propiconazole is quickly 

excreted and has no tendency for accumulation in the body. Based on these results, it is ,,~ry 

likely that propiconazole has no potential to interfere specifically with the endocrine systern. 

C. Aggregate Exposure 

1. Dietary exposure. Tier I acute, short-term, and chronic aggregate exposure 

assessments were performed for propiconazole using the Dietary Exposure Evaluation Mod:?I 

(DEEM-FCIDTM Version 3.16) from Exponent and consumption data from the USDA NHANES 
"What We Eat in America" survey, 2003-2008. Propiconazole is currently registered for uses 

on alfalfa; avocados; banana; beans (dry and succulent); beets (garden); beets (sugar); berries 

(Crop Groups 13-07A, 13-078, 13-07G); bulb vegetables (Crop Group 3); carrots; cilantro 

(leaves); citrus fruits (Crop Group 10); corn (field, pop, sweet); cranberries; grasses; leaf 

petioles (Crop Group 4B); mushrooms; nectarines; ornamentals; parsley (fresh, dried); 

peaches; peanuts; peppermint; pineapple; pistachio; rice; small cereal grains (barley, oats, rye, 

wheat); sorghum; soybean; spearmint; stone fruit (Crop Group 12}; strawberries; sugarcane; 

tomatoes; tree nuts (Crop Group 14}; turf grass, and wild rice. A use on canola is pending. IR4 

minor uses on dill, Ti palm, radish, watercress, and leafy Brassica (Crop Group SB) are 

proposed. A use on imported tea is also proposed by Tea association of USA. Existing 

(40CFR180.434} or proposed tolerances were used for all commodities. Experimental 

processing factors were used for canola meal (1.48X}, canola oil (0.03X}, orange juice (O.OllX}, 

pineapple juice (O.llX}, pineapple process residue (1.49X}, soybean oil (0.08x}, sugarcane 

sugar (0.02X}, sugarcane molasses (0.49X}, wheat bran (2.4x}, wheat flour (0.2x}. DEEM TM 

Version 7.87 default processing factors were used for all other commodities. No adjustments 

were made for "percent crop treated," i.e., 100%CT was assumed. For livestock commodities, 

established tolerances were used. Drinking water estimates were selected using the higher of 

the estimated drinking water concentrations (EDWCs) for surface and ground water. 

i. Food 

Acute Food Risk: : The acute dietary (food only) risk assessment was performed for all 

population subgroups with an acute reference dose (aRfD) of 0.3 mg/kg-bw/day based on an 

acute no observed adverse effect level (NOAEL) of 30 mg/kg-bw/day from an acute 

neurotoxicity study in rats and an uncertainly factor of lOOX. The lOOX safety factor included 

intra- and inter-species variations. No additional FQPA safety factor was applied. For the 

purpose of the aggregate risk assessment, the exposure value was expressed in terms of 

margin of exposure (MOE), which was calculated by dividing the NOAH by the exposure for 

each sub-population. In addition, exposure was expressed as a percent of the acute reference 

dose (%aRfD). At the 95th percentile, acute exposure to the U.S. population resulted in a MOE 

of 748 or 13.4% of the aRfD (Benchmark = 100; aRfD = 0.3 mg/kg-bw/day). Acute exposur~ t\J 

the most sensitive subpopulation (children 1-2 years old} resulted in a MOE of 280 or 35.6% of 

the aRfD (Benchmark = 100; aRfD = 0.3 mg/kg-bw/day). Since the Benchmark MOE for this 

assessment is 100 and since EPA generally has no concern for exposures above the benchmark 

or below 100% of the reference dose, Syngenta believes that there is a reasonable certainty 

that no harm will result from acute dietary (food) exposure to residues arising from all 

current, pending, and proposed uses for propiconazole. 
Chronic Food Risk: : The chronic dietary (food only) risk assessment was performed for all 

population subgroups with a chronic reference dose (cRfD) of 0.1 mg/kg-bw/day based on a 

24-month oncogenicity study in mice with a NOAH of 10 mg/kg-bw/day and an uncertainly 

factor of lOOX. The lOOX safety factor included intra- and interspecies variations. No 

additional FQPA safety factor was applied. For the purpose of the aggregate risk assessment, 

the exposure values were expressed in terms of margin of exposure (MOE), which was 

calculated by dividing the NOAH by the exposure for each sub-population. In addition, 

exposure was expressed as a percent of the chronic reference dose (%cRfD). Chronic exposure 

to the U.S. population resulted in a MOE of 817 or 12.2% of the cRfD (Benchmark= 100; cRfD = 

0.1 mg/kg-bw/day). Chronic exposure to the most exposed sub-population (children 1-2 years 

old) resulted in a MOE of 284 or 35.2% of the cRfD (Benchmark = 100; cRfD = 

0.1 mg/kg-bw/day). Since the Benchmark MOE for this assessment is 100 and since EPA 

generally has no concern for exposures above the benchmark or below 100% of the reference 

dose, Syngenta believes that there is a reasonable certainty that no harm will result from 

chronic dietary (food) exposure to residues arising from all current, pending, and proposed 

uses for propiconazole. 

Cancer Risk: A quantitative risk assessment using a cancer endpoint was not performed. The 

chronic risk assessment is adequately protective for cancer risk as well as other chronic 

effects. 

ii. Drinking Water. Not applicable to this import tolerance petition. 

Acute Exposure from Drinking Water. Not applicable to this import tolerance petition. 

Chronic Exposure from Drinking Water. Not applicable to this import tolerance petition. 

2. Non-dietary exposure. Not applicable to this import tolerance petition. 

D. Cumulative Effects 

Cumulative Exposure to Substances with a Common Mechanism of Toxicity. Section 

408(b)(2)(D)(v) requires that, when considering whether to establish, modify, or revoke a 

tolerance, the Agency consider "available information" concerning the cumulative effect!: '.J~ 3 

particular pesticide's residues and "other substances that have a common mechanism of 
toxicity". Propiconazole is a member of the triazole-containing class of pesticides. Although 

conazoles act similarly in plants (fungi) by inhibiting ergosterol biosynthesis, there is not 

necessarily a relationship between this pesticidal activity and their mechanism of toxicity in 

mammals. Structural similarities do not constitute a common mechanism of toxicity. There is 

currently no evidence to indicate that conazoles share common mechanisms of toxicity and 

the EPA is not following a cumulative risk approach based on a common mechanism of toxicity 

for the conazoles. 

E. Safety Determination 

1. U.S. population . . Using the conservative assumptions described above, and based 

on the completeness and reliability of the toxicity data, the acute aggregate (food plus water) 

exposure calculation for all current, pending, and proposed uses of propiconazole provided a 

MOE of 620 for the U.S. population. For short-term exposures, chronic dietary (food and 

water) exposures were aggregated with residential exposures, resulting in a worst-case shortterm aggregate MOE of 878 for the U.S. population. The chronic aggregate exposure analysis 

(food and water) showed that exposures from all current, pending, and proposed 

propiconazole uses resulted in a MOE of 630 for the U.S. population. Since the worst case 

aggregate MOE of 620 (short-term risk) exceeds the Benchmark MOE of 100, Syngenta 

believes that there is a reasonable certainty that no harm will occur to the U.S. population 

from aggregate exposures arising from all current, pending, and proposed uses for 

propiconazole. 

2. Infants and children. Using the conservative assumptions described above, and 

based on the completeness and reliability of the toxicity data, the acute aggregate (food plus 

water) exposure calculation for all current, pending, and proposed uses of propiconazole 

provided a MOE of 256 for children 1-2 years old. For short-term exposures, chronic dietary 

(food and water) exposures were aggregated with residential exposures resulting in a short 

term aggregate MOE of 376 for children 1-2 years old. The chronic aggregate exposure 

analysis (food and water) showed that exposures from all current, pending, and proposed 

propiconazole uses resulted in a MOE of 247 for children 1-2 years old. Since the worst case 

aggregate MOE of 247 (chronic risk) exceeds the Benchmark MOE of 100, Syngenta believ~s 

that there is a reasonable certainty that no harm will occur to infants and children from 

aggregate exposures arising from all current, pending, and proposed uses for propiconazole. 
F. International Tolerances 

The Codex Alimentarius Commission has established several maximum residue limits (MRLs) 

for propiconazole in or on various raw agricultural commodities (banana; barley; coffee beans; 

cranberry; maize; pecan; pineapple; popcorn; rape seed; rye; soya; sugar beet; sugar cane; 

sweet corn; triticale; wheat; and meat, milk, and eggs) but not tea. The Codex MRLs are 

expressed in terms of propiconazole per se. In addition, both Canada and Mexico have 

established MRLs/tolerances on several commodities which also have U.S. tolerances. The 

U.S. tolerance expression includes all metabolites determined as 2,4-dichloro-benzoic acid. In 

conjunction with the reregistration process EPA intends to revise the tolerance expression to 

propiconazole per se. To the extent possible, for the present petitions, U.S. tolerances have 

been numerically harmonized with Canadian MRL in tea.