 Page 1 of 28 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM Date: 15 February 2006 Subject: Terbacil. Section 3 Registration for Application to Watermelon. HED Risk Assessment.

Registration: 3E6640 DP #: D327041 Decision #: 354086 PC Code: 012701 From: Tom Bloem, Chemist Lisa Austin, Ph. D., Toxicologist Mark Dow, Ph. D., Biologist Registration Action Branch 1 ( RAB1) Health Effects Division ( HED; 7509C)

Through: PV Shah, Ph. D., Branch Senior Scientist RAB1/ HED ( 7509C)

To: Dan Rosenblatt ( RM 05) Registration Division ( RD; 7505C)

The HED of the Office of Pesticide Programs ( OPP) is charged with estimating the risk to human health from exposure to pesticides. The RD of OPP requested that HED evaluate hazard and exposure data and conduct dietary, occupational, residential, and aggregate exposure assessments, as needed, to estimate the risk to human health that will result from all registered and proposed uses of terbacil. A summary of these findings is provided in this document. The risk assessment, residue chemistry review, and dietary exposure assessment were provided by Tom Bloem of RAB1; the hazard characterization was provided by Lisa Austin of RAB1; the occupational/ residential exposure and risk assessment was provided by Mark Dow of RAB1; and the drinking water assessment was provided by Ibrahim Abdel Shaib of the Environmental Fate and Effects Division ( EFED). Page 2 of 28 Table of Contents 1.0 Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2.0 Ingredient Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2.1 Summary of Registered/ Proposed Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2.2 Structure and Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.3 Physical and Chemical Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 3.0 Hazard Characterization/ Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3.1 Hazard and Dose Response Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3.2 Absorption, Distribution, Metabolism Excretion ( ADME) . . . . . . . . . . . . . . . . . . . . . . 11 3.3 FQPA Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 3.4 FQPA Safety Factor for Infants and Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 3.5 Hazard Identification and Toxicity Endpoint Selection . . . . . . . . . . . . . . . . . . . . . . . . 15 3.6 Endocrine Disruption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 4.0 Public Health and Pesticide Epidemiology Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 5.0 Dietary Exposure/ Risk Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 5.1 Metabolism and Environmental Degradation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 5.2 Watermelon, Rotational Crop, and Drinking Water Residue Profile . . . . . . . . . . . . . . . 19 5.3 Dietary Exposure and Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 6.0 Residential ( non occupational) Exposure/ Risk Characterization . . . . . . . . . . . . . . . . . . . . 22 7.0 Aggregate Risk Assessments and Risk Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . 23 8.0 Cumulative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 9.0 Occupational Exposure/ Risk Pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 9.1 Handler Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 9.1 Postapplication Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 10.0 Data Needs and Label Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 10.1 Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 10.2 Residue Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 10.3 Occupational/ Residential Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Page 3 of 28 1.0 Executive Summary Background: Terbacil provides control of annual grasses and broadleaf weeds via photosynthesis inhibition ( inhibition of photosystem II). Terbacil is readily absorbed by roots and translocated upward; when absorbed by leaves, translocation is minimal.

Tolerances are currently established for the combined residues of terbacil and its metabolites 3 tert butyl 5 chloro 6 hydroxymethyluracil ( metabolite A), 6 chloro 2,3 dihydro 7 hydroxymethyl 3,3 dimethyl 5H oxazolo ( 3,2 a) pyrimidin 5 one ( metabolite B), and 6 chloro 2,3 dihydro 3,3,7 trimethyl 5H oxazolo ( 3,2 a) pyrimidin 5 one ( metabolite C), calculated as terbacil, in/ on alfalfa, apple, asparagus, blueberry, caneberry, peach, peppermint, spearmint, strawberry, and sugarcane ranging from 0.1 2.0 ppm ( 40 CFR180.209; see attachment 1 for structures). A time limited tolerance in/ on watermelon is also established at 0.4 ppm ( expires 30 Jun 2007; Section 18 registration).

The Interregional Research Project Number 4 ( IR 4) proposed a Section 3 registration for application of terbacil to watermelon and establishment of a 1 ppm tolerance in/ on watermelon for the combined residues of terbacil and its metabolites A, B, and C.

Hazard Assessment: Terbacil was minimally toxic by the oral, dermal, and inhalation routes ( Toxicity Category IV) in acute studies. It was mildly irritating to the eye ( Toxicity Category III). It is neither a dermal irritant nor sensitizer. The acute dermal and primary skin irritation studies submitted to the EPA were performed with an 80% wettable powder ( WP) formulation of terbacil.

The critical effects were increased liver weight ( relative and absolute), vacuolation, focal necrosis, triaditis, hepatocyte hypertrophy, decreased body weight and body weight gain. In general, these effects were observed in both sexes in rats and mice. However, in the dog ( both sexes), the critical effect was thymic involution. The dog was also the most sensitive species to terbacil toxicity. Terbacil was negative in a variety of genotoxicity screening assays. Thus, it appears that terbacil is not a genotoxic chemical. This chemical was previously classified by the HED RfD/ Peer Review Committee as Group E, evidence of non carcinogenicity for humans ( TXR No. 011277, 30 Sep 1994). In accordance with current guidelines, terbacil is classified as not likely to be carcinogenic to humans based on the lack of evidence of carcinogenicity in a carcinogenicity study in mice and two combined chronic toxicity/ carcinogenicity studies in rats.

There is no evidence of increased fetal susceptibility in rats or rabbits based on developmental studies in the rat and rabbit and the multi generation reproduction study in the rat. Terbacil induced a decrease in the number of live fetuses/ litter in rats at a dose higher than the dose which caused maternal toxicity ( decreased body weight gain). In rabbits, the developmental effects were decreased body weight, increased incidence of skeletal malformations ( fused ribs) and increased frequency of skeletal variations. These effects occurred at the same dose that induced maternal toxicity ( mortality, anorexia, discharge, decreased body weight and body weight gain). Reproductive performance was not affected at the highest dose ( 250 ppm) tested in the 3 generation reproduction study in rats. Page 4 of 28 Dose Response: Based on HED's review of the toxicological data, the following endpoints were used to assess dietary and occupational exposure to terbacil. HED reduced the Food Quality Protection Act Safety Factor ( FQPA SF) to 1x based on toxicological considerations and residue assumptions used in the dietary analyses.

Table 1: Summary of Toxicological Endpoints used in this Assessment acute dietary ( all population subgroups) An endpoint of concern attributable to a single dose for the general population and females 13+ was not identified.

chronic dietary NOAEL = 1.4 mg/ kg/ day chronic RfD and cPAD1 = 0.014 mg/ kg/ day dermal ( all durations) Quantification of dermal risk is not required; the lack of dermal or systemic toxicity at 5000 mg/ kg ( 5X the limit dose) in a 21 day dermal toxicity study in rats which indicates poor dermal absorption.

short term inhalation ( 1 30 days) oral NOAEL = 2.0 mg/ kg/ day Target MOE2 $ 100 ( occupational)

cancer Classification: Not likely to be carcinogenic to humans; cancer risk assessment is not required.

1 cPAD = chronic population adjusted dose = cRfD ÷ FQPA SF 2 MOE = margin of exposure = NOAEL ÷ estimated exposure Occupational Exposure and Risk Assessment: Based upon the proposed use pattern and the lack of dermal endpoints ( see previous section), HED anticipates only short term ( 1  30 days) inhalation exposures to non commercial handlers. Post application inhalation exposures are not anticipated as it is expected that the spray solution will have dried after the labeled specified 12 hour restricted reentry interval ( REI). Since no chemical specific data were available with which to assess pesticide handler exposure, the surrogate data from studies in the Pesticide Handler Exposure Database Version 1.1 ( August 1998) PHED SURROGATE EXPOSURE GUIDE were used to estimate mixer/ loader and applicator exposure. It is HED policy to assess handler exposure and risk using " baseline" personal protective equipment ( PPE) which is comprised of long sleeved shirt, long pants, and shoes plus socks and if necessary to assess " baseline" plus the use of protective gloves or other PPE as might be necessary or appropriate. The resulting MOEs were 108 for the mixer/ loader and 6300 for the applicator and are therefore less than HED's level of concern.

Aggregate Exposure and Risk Assessment: Since there are no registered/ proposed uses which result in residential exposures, only a chronic aggregate risk assessment, considering exposure from food and water, is necessary ( acute endpoint was not identified and terbacil is classified as not likely to be carcinogenic to humans). The chronic dietary exposure assessments were conducted using the Dietary Exposure Evaluation Model  Food Consumption Intake Database ( DEEM FCID   , ver. 2.03) model which incorporates data from the USDA's Continuing Surveys of Food Intakes by Individuals ( CSFII; 1994 1996 and 1998). The chronic dietary analysis assumed tolerance level residues, 100% crop treated, and DEEM ( ver 7.81) default processing factors for all registered/ proposed crops. The SCI GROW ( Screening Concentration in Ground Water) modeled water estimate was assumed for all water sources ( direct and indirect). Although rotational crop tolerances are not currently established, based on the available field rotational crop data and the application rates, residues in/ on crops rotated into alfalfa, sugarcane, and mint fields which were treated with terbacil are possible ( alfalfa, sugarcane, and mint are registered crops). Page 5 of 28 Therefore, the analysis incorporated a conservative residue estimates for cereal grains and soybean ( these crops are commonly rotated with alfalfa, sugarcane, and mint). The chronic dietary exposure estimates were # 99% the cPAD and are therefore less than HED's level of concern ( all infants < 1 year were the most highly exposed population subgroup).

HED notes that the assessment assumes, based on cultural practices, that only cereal grains and soybean are rotated into alfalfa, sugar cane, and mint fields while the registered application scenario for these crops permits the rotation of any crop. When the residue estimates used to generate the dietary exposure estimates are taken in total ( SCI GROW drinking water estimates; tolerance level residue and 100% crop treated for all registered/ proposed crops), HED concludes that exposure to terbacil is likely to be significantly lower than the estimates provided in this document.

Recommendations for Tolerances/ Registration: Provided the petitioner submits a revised Section F and the Analytical Chemistry Laboratory ( ACL) of the Biological and Economic Analysis Division ( BEAD) is able to validate the proposed plant enforcement method, HED concludes that the toxicological, residue chemistry, and occupational/ residential databases support a conditional registration and establishment of 1.0 ppm tolerance for the residues of terbacil and its metabolites A, B, and C in/ on watermelon.

Unconditional registration may be established upon submission of data which adequately address the following deficiencies:

CFood and Drug Administration ( FDA) multiresidue testing of terbacil and its metabolites A, B, and C through protocol D Cadditional watermelon field trials, conducted with application after crop emergence, in Regions 3 ( n= 1), 5 ( n= 1), and 6 ( n= 1) Page 6 of 28 2.0 Ingredient Profile 2.1 Summary of Registered/ Proposed Uses Registered: Terbacil is currently registered for application to alfalfa, apple, asparagus, blueberry, caneberry, peach, peppermint, spearmint, strawberry, and sugarcane with tolerances for the combined residues of terbacil and metabolites A, B, and C, expressed as terbacil, ranging from 0.1 2.0 ppm ( 40 CFR180.209). A section 18 registration for application of terbacil to watermelon is currently established with a time limited tolerance of 0.4 ppm ( expires 30 Jun 2007). Based on the HED Reregistration Eligibility Document ( RED; D. Miller, 18 Dec 1996) and the Section 18 watermelon risk assessment ( D231995 and D231994, G. Herndon, 29 Jan 1997), terbacil application rates for the currently registered crops range from 0.1 4.8 lbs ai/ acre/ season.

Proposed: The petitioner provided a supplemental Dupont   Sinbar ® Herbicide ( WP; 80% terbacil by weight; EPA Reg. No. 352 317) label which includes instructions for application to watermelon. Table 2 is a summary of the proposed application scenario.

The supplemental label indicates that for seeded watermelon, applications are to be made after planting but before the crop emerges; however, application to emerged crops is also permitted since the supplemental label cautions that the spray solution should not be allowed to contact the crop ( over the top applications are prohibited). No rotational crop restrictions are included on the supplemental label; however, the supplemental label states that all applicable directions, restrictions, and precautions on the main label must be followed. The main label indicates that no crops may be planted within 2 years of application as injury to the subsequent crops may result. The main label also indicates that application through irrigation equipment is prohibited and that unless otherwise directed, the product is to be applied with a fixed boom power sprayer.

The Sinbar ® label directs applicators and other handlers to wear long sleeved shirt, long pants, chemical resistant gloves ( such as butyl, natural, neoprene or nitrile rubber) $ 14 mils and shoes plus socks. A REI of 12 hours is specified.

HED concludes that the proposed application instructions are adequate.

Table 2: Summary of Proposed Application Scenario for Terbacil Application Equipment Max. Single Applic. Rate ( lb ai/ acre) Max. No. Applic. per Season PHI1 ( days) Comments Watermelon ground equipment; fixed boom power sprayer 0.10 0.15 1 70 lower rate is for coarse texture soils lower in organic matter; 20 40 gallon/ acre 1 PHI = preharvest interval Page 7 of 28 N HN O C( CH3) 3 O Cl H3C 2.2 Structure and Nomenclature Table 3: Test Compound Nomenclature.

Chemical structure Common name terbacil Company experimental name DPX D0732 IUPAC name 3 tert butyl 5 chloro 6 methyluracil CAS name 5 chloro 3( 1,1 dimethylethyl) 6 methyl 2,4( 1H, 3H) pyrimidinedione CAS registry number 5902 51 2 End use product ( EP) Sinbar ® 80WP ( 80% terbacil)

2.3 Physical and Chemical Properties Table 4: Physicochemical Properties of the Technical Grade Test Compound.

Parameter Value Reference Melting point/ range 175 177 ° C Terbacil Reregistration Standard ( 8 Mar 1989, R. Schmitt) pH not available Density 1.34 g/ cm3 ( 25 /

C)

Water solubility ( mg/ L ( 25 ° C)) 710 Solvent solubility ( mg/ mL ( 25 ° C)) dimethylformamide 33.7 cyclohexane 22 methyl isobutyl ketone 13.8 butyl acetate 9.7 Xylene 6.5 Vapor pressure 4.7 x 10 7 mm Hg ( 29.5 /

C)

Dissociation constant, pKa not available Octanol/ water partition coefficient ( KOW) 81.9 UV/ visible absorption spectrum not available Page 8 of 28 3.0 Hazard Characterization/ Assessment 3.1 Hazard and Dose Response Characterization Terbacil was minimally toxic by the oral, dermal and inhalation routes ( Toxicity Category IV) in acute studies. It was mildly irritating to the eye ( Toxicity Category III). It is neither a dermal irritant nor sensitizer. The acute dermal and primary skin irritation studies submitted to the EPA were performed with an 80% WP formulation of terbacil. Table 4 is a summary of the acute toxicity profile for terbacil.

The critical effects were increased liver weight ( relative and absolute), vacuolation, focal necrosis, triaditis, hepatocyte hypertrophy, decreased body weight and body weight gain. In general, these effects were observed in both sexes in rats and mice. However, in the dog ( both sexes), the critical effect was thymic involution. The dog was also the most sensitive species to terbacil toxicity. Terbacil was negative in a variety of genotoxicity screening assays. Thus, it appears that terbacil is not a genotoxic chemical. This chemical was previously classified by the HED RfD/ Peer Review Committee as Group E, evidence of non carcinogenicity for humans ( TXR No. 011277, 30 Sep 1994). In accordance with current guidelines, terbacil is classified as not likely to be carcinogenic to humans based on the lack of evidence of carcinogenicity in a carcinogenicity study in mice and two combined chronic toxicity/ carcinogenicity studies in rats.

There is no evidence of increased fetal susceptibility in rats or rabbits based on developmental studies in the rat and rabbit and the multi generation reproduction study in the rat. Terbacil induced a decrease in the number of live fetuses/ litter in rats at a dose higher than the dose which caused maternal toxicity ( decreased body weight gain). In rabbits, the developmental effects were decreased body weight, increased incidence of skeletal malformations ( fused ribs) and increased frequency of skeletal variations. These effects occurred at the same dose that induced maternal toxicity ( mortality, anorexia, discharge, decreased body weight and body weight gain). Reproductive performance was not affected at the highest dose ( 250 ppm) tested in the 3 generation reproduction study in rats.

There was no appreciable difference in the absorption, distribution, and metabolism of radioactivity in rats with regard to dose and sex. Terbacil was rapidly absorbed, metabolized and eliminated. The total excretion of terbacil was 91 to 103% of radioactivity within 5 days following dosing. The primary routes of elimination were the urine ( 55  68%, 66 81%) and feces ( 2 14%, 10 25%) within 24 and 48 hours of dosing, respectively. Radioactivity recovered in tissues accounted for less than 0.3% of the administered dose. The highest residue levels were found in the gastrointestinal tract ( 0.04 0.23% of the dose) and whole blood ( 0.04 0.06% of the dose). Excretion in expired air accounted for less than 0.5% of the dose.

Eight metabolites were detected in the urine, a 6 hydroxymethyl derivative ( metabolite A), glucuronide ( DF1), sulfate ( EF2), and sulfate/ N acetylcysteine ( EF1/ EF3) conjugates and 3 unidentified metabolites. The major metabolites were DF1, EF2 and EF1/ EF3. These same metabolites, with the exception of EF2, were identified in the feces. There were five unidentified metabolites detected in the feces. The primary metabolic pathway is hydroxylation of the 6 methyl group to form an alcohol which is conjugated to form the glucuronide ( 35% of the dose) and the sulfate derivatives ( 11%). Terbacil is also metabolized to the 5 hydroxy intermediate, which is further conjugated to form a sulfate derivative ( 17%). Page 9 of 28 Table 4: Acute Toxicity of Terbacil Guideline No. Study Type MRID # Results Toxicity Category 870.1100 ( 81 1) Acute Oral ( rat) 12235 LD50 > 5000 mg/ kg IV 870.1200 ( 81 2) Acute Dermal ( rabbit)* 00114963 LD50 > 5000 mg/ kg IV 870.1300 ( 81 3) Acute Inhalation ( rat) 00125700 LC50 > 4.4 mg/ L IV 870.2400 ( 81 4) Primary Eye Irritation ( rabbit) 00157179 Mild irritant III 870.2500 ( 81 5 ) Primary Skin Irritation1 ( rabbit) 125785 Not a dermal irritant IV2 87.2600 ( 81 6) Dermal Sensitization ( guinea pig) 00157180 Not a dermal sensitizer N/ A 1 Studies conducted with a 80WP formulation. 2 Based on a 21 day dermal toxicity study in rabbits.

Table 5: Toxicity Profile of Terbacil Guideline No./ Study type MRID No.( year)/ classification/ Doses Results 870.3100 90 Day Oral [ rat] 00068035 ( 1965) 0, 100, 500 and 5000 ppm( equivalent to0, 8, 20, 200 mg/ kg/ day) acceptable/ guideline NOAEL = 500 ppm ( 20 mg/ kg/ day) LOAEL = 5000 ppm ( 200 mg/ kg/ day), based on focal necrosis and triaditis in females, vacuolization in males and increased relative liver weight and hypertrophy of hepatocytes in both sexes.

870.3200 21 Day Dermal [ rabbit] 125785 ( 1965) 0 and 5000 mg/ kg/ day acceptable/ non guideline NOAEL = 5000 mg/ kg/ day LOAEL was not established There were no clinical signs of toxicity, gross or histopathologic changes.

870.4100 Chronic Oral [ 2 years dog] 00060851( 1966) 0, 50, 250, 2500/ 10000 ppm ( equivalent to 0, 1.0, 5.0, 50/ 200) mg/ kg/ day mg/ kg/ day acceptable/ guideline NOAEL = 250 ppm ( equivalent to 5.0 mg/ kg/ day) LOAEL = 2500 ppm ( equivalent to 50 mg/ kg/ day), based on increased relative thyroid weights and thymic involution in both sexes.

870.4200 Carcinogenicity [ mouse] 00126770 ( 1981) M/ F: 0/ 0, 6.5/ 8.0, 162/ 199, 746/ 895 mg/ kg/ day acceptable/ guideline NOAEL = 162 mg/ kg/ day LOAEL = 746 mg/ kg/ day, based on increased liver weights, hyperplastic nodules, necrosis, and vacuolation in the liver in males. There was no oncogenic potential at the doses tested.

870.3700 Developmental Toxicity [ rat] 00050467 ( 1980) 0, 24, 104 and 392 mg/ kg/ day acceptable/ guideline Maternal NOAEL was not established Maternal LOAEL = 24 mg/ kg/ day based on decreased body weight gain. Developmental NOAEL = 24 mg/ kg/ day Developmental LOAEL = 104 mg/ kg/ day, based on decreased number of live fetuses/ litter.

870.3700 Developmental Toxicity [ rabbit] 00150945 ( 1984) 0, 30, 200, and 600 mg/ kg/ day acceptable/ non guideline Maternal NOAEL = 200 mg/ kg/ day Maternal LOAEL = 600 mg/ kg/ day, based on mortality, clinical findings ( anorexia, discharge), decreased body weight and body weight gain. Developmental NOAEL= 200 mg/ kg/ day Developmental LOAEL = 600 mg/ kg/ day, based on decreased body weight, increased incidence of skeletal malformations ( fused ribs) and increase frequency of skeletal variations. Table 5: Toxicity Profile of Terbacil Guideline No./ Study type MRID No.( year)/ classification/ Doses Results Page 10 of 28 870.3800 3 generation reproduction [ rat] 0060852 ( 1967) 0, 50, and 250 ppm ( equivalent to 0, 2.0, and 10 mg/ kg/ day) acceptable/ non guideline Parental NOAEL = 50 ppm ( equivalent to2.0 mg/ kg/ day) Parental LOAEL = 250 ppm ( equivalent to 10 mg/ kg/ day) based on decreased body weight, Reproductive NOAEL = 250 ppm ( equivalent to 10 mg/ kg/ day) Reproductive LOAEL was not established Offspring NOAEL = 250 ppm ( equivalent to 10 mg/ kg/ day) Offspring LOAEL was not established 870.4300 Combined Chronic Toxicity/ Carcinogenicity [ rat] 42987601 ( 1993) M/ F: 0/ 0, 0.9/ 1.4, 58/ 83, 308/ 484 mg/ kg/ day acceptable/ guideline NOAEL ( M/ F)= 58/ 1.4 mg/ kg/ day LOAEL ( M/ F)= 308/ 83 mg/ kg/ day, based on decreased body weight and body weight gain and increased absolute and relative liver weights in males and females. There was no oncogenic potential at the doses tested.

870.4300 Combined Chronic Toxicity/ Carcinogenicity [ rat] 00060850 ( 1966) 0, 50, 250, and 2500/ 10000 ppm ( equivalent to 0, 2.0, 10 and 100/ 400 mg/ kg/ day) acceptable/ guideline Systemic NOAEL = 250 ppm ( equivalent to 10 mg/ kg/ day) Systemic LOAEL = 2500/ 10000 ppm ( equivalent to 100/ 400 mg/ kg/ day) based on increased mean relative liver weights, hepatocyte centrilobular hypertrophy in males and females and vacuolation in females. There was no oncogenic potential at the doses tested.

870.5300 Mutagenic ( HGPRT) 00150943 ( 1984) unacceptable Pages missing in report.

870.5300 Mutagenic ( HGPRT) 00260460 ( 1984) 0, 2, 3, 5 and 6 mM ( S9); 0, 1, 2, 2.5, 2.75, 3.25 and 3.50 mM (+ S9) acceptable/ guideline Did not induce mutation in chinese hamster ovary cells with or without metabolic activation.

870.5375 in vitro chromosome aberration assay [ CHO cells] 00150944 ( 1984) 0, 20, 100 and 500 mg/ kg acceptable/ guideline Negative for clastogenic activity in the rat bone marrow cytogenetic assay.

870.5500 unscheduled DNA synthesis assay rat primary hepatocyte 00150939 ( 1984) 0, 0.010, 0.033, 0.10, 0.33, 1.0, 2.5, 5.0, 7.5, and 10 mM acceptable/ guideline Did not induce unscheduled DNA synthesis in primary rat hepatocytes.

870.5100 Mutagenicity Study ( bacteriophage assay) 12178 ( 1965) acceptable/ non guideline Did not show the suspected ( 5 bromo uracil metabolite) mutagenic action.

870.7485 Metabolism Study in Rats 40104702 ( 1986) single doses of 6.5 or 500 mg/ kg acceptable/ guideline Approximately 57 82% of the administered dose was absorbed in 24 hours. Ninety one to 103% of radioactivity was recovered within 5 days; with 70 to 86% in urine and 14 28% in feces. The major metabolites were glucuronide, sulfate and sulfate/ Nacetylcysteine conjugates. The primary metabolic pathway is hydroxylation of the 6 methyl group to form the alcohol which is conjugated to form the glucuronide ( 35% of the dose) and the sulfate derivatives ( 11%). Terbacil is also metabolized to the 5 hydroxy intermediate, which is further conjugated to form a sulfate derivative ( 17%). There was no evidence suggestive of bioaccumulation.

M  Male; F  Female Page 11 of 28 3.2 Absorption, Distribution, Metabolism Excretion ( ADME)

In rats, terbacil was well absorbed, distributed, metabolized and excreted. Urine and feces were found to be major routes of excretion for terbacil. There were no significant gender differences. At 24 hours post exposure, 55 68% of the radioactivity was eliminated in the urine; 2 14% was eliminated in the feces. At 48 hours, 66 81% was eliminated in the urine; 10 25% in the feces. At 120 hours ( 5 days) post exposure, for all dose groups, 70 to 86% of the dose was excreted in the urine and 14 to 28% was excreted in the feces. Based on excretion, approximately 57 82% of the administered dose was absorbed in 24 hours. Tissues collected and analyzed for radioactivity accounted for less than 0.3% of the administered dose. The highest residue levels were found in the gastrointestinal tract ( 0.04 0.23% of the dose) and whole blood ( 0.04 0.06% of the dose). Excretion in expired air accounted for less than 0.5% of the dose.

The unmetabolized parent compound was not identified in urine or feces; however, 8 metabolites were detected in the urine and feces. The major metabolites identified in the urine were glucuronide ( DF1, 20 39%), sulfate ( EF2, 13 17.9%) and sulfate/ N acetylcysteine ( EF1/ EF3, 8.5 14 %) conjugates. The major metabolites in the feces were DF1 ( 1 2%), EF1/ EF3 ( 0.7 2%) and 6 hydroxydervative, DF4 ( 2%).

The proposed metabolic pathway for terbacil in rats involved the hydroxylation of the 6 methyl group to form an alcohol which is extensively conjugated to form the glucouronide and sulfate derivatives. Terbacil is also metabolized to the 5 hydroxy intermediate, which is further conjugated to form a sulfate derivative.

3.3 FQPA Considerations Adequacy of the Toxicity Data Base: The toxicology database for terbacil is adequate. The following acceptable studies are available: Developmental toxicity in rats and rabbits and threegeneration reproduction study in rats.

Evidence of Neurotoxicity: There is not a concern for neurotoxicity resulting from exposure to terbacil. Acute and subchronic neurotoxicity studies were not performed. No clinical signs of neurotoxicity or neuropathology were observed in the subchronic and chronic studies; therefore, the chemical is not considered neurotoxic.

Developmental Toxicity Studies: The registrant has submitted rat and rabbit developmental studies and a rat multigenration study. The following paragraphs are summaries of these data.

Rat Developmental Study ( MRID 00050467): Terbacil ( 96.6 % a. i., Lot#: T 811115 D) was administered to pregnant ChR CD © rats ( 27/ dose) at dose levels of 0, 250, 1250, or 5000 ppm ( 0, 24, 104. and 392 mg/ kg/ day) by diet on gestation days ( GDs) 6 through 15. No premature deaths occurred during the study. All dams were sacrificed on GD 21.

There were no effects of treatment on mortality, clinical signs, or gross pathology. A significant ( p< 0.05) decrease in average body weight gain was observed in the mid ( 38%) and high ( 68%) dose groups on GD 6 10, and in all treatment groups on GD 10 16 ( 15%, 21%, 18% at 250, 1250 and 5000 ppm, respectively). This was accompanied by a dose dependent decrease in mean Page 12 of 28 body weight that reached significant levels ( p< 0.05) at 1250 ( 5%, 8%, 6%) and 5000 ppm ( 10%, 10%, 8%) on GD 10, 16, and 21, respectively, relative to controls. Food consumption was significantly decreased relative to controls in the mid ( 21%, 34%) and high ( 13%, 14%) dose groups on GD 6 10 and 10 16, respectively.

The maternal LOAEL was 250 ppm ( 24 mg/ kg/ day) based on decreased body weight gain. The maternal NOAEL was not observed.

There was no significant difference between the control and treated groups in pregnancy rate or number of abortions, resorptions, or dead fetuses. The mean number of implantations per litter was significantly lower ( p< 0.05) relative to controls ( 11.4 + 2.3) at 5000 ppm ( 9.3 + 3.1) and the effect was dose dependent. The mean number of live fetuses per litter decreased in a dosedependent manner and was significant ( p< 0.05) at 1250 ( 9.1 + 3.2) and 5000 ppm ( 8.6 + 2.9) relative to controls ( 10.9 + 2.0). A dose dependent increase relative to controls in litters with early resorption ( 24%, 24% and 48%) and litters partially resorbed ( 19%, 19%, and 29%) was observed at 250, 1250 and 5000 ppm, respectively. However, the differences were not statistically significant and the mean number of resorption/ litter and resorptions was similar across treatment group. There was a significant increase of fetuses with dilation of the renal pelvis and/ or hydroureter observed in all treated groups ( 4/ 22, 6/ 22, 4/ 22) relative to control ( 0/ 19); these effects were not dose dependent. Additionally, the recorded incidences were within range of historical control values as reported by DuPont in a response to concerns regarding the increase in dilation of the renal pelvis and/ or hydrourteter during the 1982 Registration Standard. The response was accepted ( Tox. Doc. No. 003401). No statistically or biologically significant increases in gross and skeletal malformations were detected.

The developmental LOAEL is 1250 ppm ( 104 mg/ kg) based on decreased number of live fetuses/ litter. The developmental NOAEL is 250 ppm ( 24 mg/ kg).

The developmental toxicity study in rats is classified Acceptable/ Non guideline ( § 83 3[ a]), and does not satisfy the guideline requirements for a developmental toxicity study in the rat because of the following deficiencies: treatment occurred during GD 6 15 instead of GD 6 21, individual data on fetal sex and body weight, gravid uterine weight, body weight adjusted for gravid uterine weight. However, this study is adequate to evaluate the teratogenic susceptibility of rats to terbacil.

Rabbit Developmental Study ( MRID 00150945): Terbacil [ 96.1% a. i. in 0.5% methyl cellulose vehicle] was administered to 18 artificially inseminated New Zealand White female rabbits/ group via gavage at dose levels of 0 ( 0.5% methyl cellulose vehicle), 30, 200, and 600 mg/ kg body weight/ day from days 7 through 19 of gestation. Surviving does were sacrificed on GD 29 and their fetuses were removed by cesarean and examined.

Maternal mortality was significantly ( p< 0.05) increased among does in the 600 mg/ kg group. 4/ 18 does died and 1/ 18 was sacrificed in extremis during the treatment period. During posttreatment 1/ 18 doe died and 1/ 18 was sacrificed in extremis. There was a significant ( p< 0.05) decrease in body weight gain in the high dose group ( 0.19 kg vs 0.06 kg in controls). There were also significant incidences of anorexia ( 15/ 18) and semi solid and watery yellow ( 7/ 18), Page 13 of 28 orange or red discharges ( from GD day 19). Trichobezoars filled the stomachs completely in 11/ 18 does at dose levels of 600 mg/ kg/ day versus 5/ 18 in the control group. Mild gastric lesions were observed microscopically in the control and high dose groups but were considered secondary to the formation of trichobezoars. The incidences of these lesions were not significantly different between the two groups.

The maternal toxicity LOAEL is 600 mg/ kg/ day based on mortality, clinical finding ( anorexia, discharge) and decreased bodyweight gain. The maternal NOAEL was 200 mg/ kg/ day.

There was no significant difference between the control and treated groups in pregnancy rate or in the number of nidations, abortions, resorptions, live and dead fetuses. Fetal toxicity at 600 mg/ kg/ day was demonstrated by a significant decrease in fetal body weight ( 17%). There was a 184% increase relative to controls, in the percentage of malformed fetuses/ litter and a significantly higher incidence of fused ribs in the 600 mg/ kg group relative to controls ( 7% pups in 50% litters vs 0% in controls). Also, a significant increase in the frequencies of extra ribs ( 2.8X controls) and partially ossified or unossified phalanges ( 30% vs 3%) and pubes ( 48% vs 18%) was observed relative to controls.

The developmental toxicity LOAEL is 600 mg/ kg/ day based on decreased body weight, increased incidence of skeletal malformations ( fused ribs) and an increased frequency of skeletal variations ( extra ribs and partially ossified or unossified phalanges and pubes). The developmental NOAEL was 200 mg/ kg/ day.

The developmental toxicity study in the rabbit is classified Acceptable/ Non guideline. This study does not satisfy the guideline requirement for a developmental toxicity study [ OPPTS 870.3700; § 83 3( b)] in the rabbit, because of inadequate study duration. Other deficiencies noted included no measurement of food consumption, gravid uterine weights, body weights adjusted for gravid uterine weights, and no historical control data. In addition, dead fetuses were not examined for external or visceral anomalies. However, this study is considered adequate to evaluate the teratogenic potential of terbacil in developing rabbits during the period of organogenesis.

Rat Multigeneration Reproduction Study ( MRID 0060852): Terbacil technical ( Batch # 1, 80%) was administered in the diet continuously to 3 generations of albino CD rats ( 10 males/ 20 females/ dose) at dose levels of 0, 50 and 250 ppm ( 0, 2.0 and 10 mg/ kg/ day). Parental animals from every generation underwent 2 breeding cycles. Two females were mated with one male; each cycle with a different male. Pups from the 1st litter ( 1st breeding cycle) of all matings were examined for abnormalities and sacrificed. Representative pups ( 10 males/ 20 females/ dose) from the 2nd litter ( 2nd breeding cycle) of all matings were selected as parental rats for the succeeding generation. Observations were recorded for 10 mice/ sex/ dose of the 2nd breeding cycle in each generation.

There were no treatment related clinical signs or mortalities. Mean body weight was decreased in a dose dependent manner in P 1 ( 9%, 10%), P 2 ( 4%, 17%), and P 3 ( 5%, 9%) males and P 2 females ( 8%, 10%) at 50 and 250 ppm, respectively, relative to controls after 33, 33 and 26/ 33 weeks, respectively. Weekly mean food consumption per rat was increased in P 1 males ( 3%, 14%) and Page 14 of 28 decreased in P 2 males ( 4%, 4%) and females ( 8%, 13%) and P 3 males ( 9%, 10%) at 50 and 250 ppm, respectively, relative to controls. P 3 males exhibited a 10 13% decrease in body weight gain in the last 12 weeks of treatment.

There was a dose dependent increase in relative adrenal weights in P 3 females ( 15%, 21%) relative to controls at 50 and 250 ppm, respectively. Relative and/ or absolute weights were increased in various organs in females at both doses. However, in the absence of histopathological changes, changes in organ weights were not regarded as toxicologically significant.

The fertility index for F 2B females decreased to 45% at 250 ppm; however, this effect was not dose dependent and fell within the historical control range ( 14 90%). The number of litters per group, total number of stillbirths, live births, percent survival, mean body weight at weaning and the reproductive capabilities of rats fed terbacil in the diet were comparable to those of control rats in each generation.

The LOAEL for systemic parental toxicity was 250 ppm ( equivalent to 10 mg/ kg/ day) based on decreased body weight in both sexes. The NOAEL was 50 ppm ( equivalent to2.0 mg/ kg/ day). The LOAEL for systemic offspring toxicity was not established. The offspring NOAEL is 250 ppm ( equivalent to 10 mg/ kg/ day). The LOAEL for reproductive toxicity was not established. The reproductive NOAEL is 250 ppm ( equivalent to 10 mg/ kg/ day).

The study was done prior to implementation of Good Laboratory Practices ( GLP) Guidelines, therefore, does not fall under the purview of either GLP Guidelines or Quality Assurance requirements. It was reviewed for the 1982 Registration Standard, and graded coresupplementary based on testing only 2 dose levels and the use of antibiotics on the test animals during the study. The study was upgraded to core minimum ( Tox. Doc. 003401) after the registrant addressed concerns ( Acc. No. 249455) regarding unavailable necropsy records for the first litters and incomplete breeding records. The study is classified as Acceptable/ Non guideline and satisfies the regulatory requirements ( § 83 4[ a]) for a multigenerational reproductive toxicity study in rats.

Pre and/ or Postnatal Toxicity: There is no evidence of increased susceptibility in rat and rabbit fetuses to in utero exposure to terbacil. There is no evidence of increased susceptibility to terbacil following prenatal exposure in a 3 generation reproduction study in rats.

Degree of Concern Analysis and Residual Uncertainties: There are no residual uncertainties or concerns for increased susceptibility; there are well established NOAELs and LOAELs in the developmental and reproduction studies.

Recommendation for a Developmental Neurotoxicity Study: There is not a concern for developmental neurotoxicity resulting from exposure to terbacil. There is no indication of neurotoxicity observed in any other subchronic or chronic toxicity studies. Based on the available data from multiple studies, the chemical is not considered neurotoxic, thus, a developmental neurotoxicity study is not required for terbacil. Page 15 of 28 3.4 FQPA SF for Infants and Children HED concludes that the FQPA SF can be reduced to 1x for the following reasons: ( 1) there is no evidence of increased susceptibility in rat and rabbit fetuses to in utero exposure to terbacil; ( 2) there is no evidence of increased susceptibility to terbacil following prenatal exposure in a 3 generation reproduction study in rats; ( 3) there are no residual toxicological uncertainties or concerns for increased susceptibility; ( 4) there are well established NOAELs and LOAELs in the developmental and reproduction studies; ( 5) the environmental fate database is adequate to access the nature and magnitude of the residue in drinking water; ( 6) the dietary exposure analysis assumed tolerance level residues and 100% crop treated.

3.5 Hazard Identification and Toxicity Endpoint Selection The following text and Table 6 are summaries of the endpoints chosen by HED for oral, dermal, and inhalation risk assessment.

Acute Dietary Endpoint: Acute dietary endpoints for child bearing females ( Females 13+) and the general population including infants and children, were not established since an endpoint of concern attributable to a single dose was not identified.

Chronic Dietary Endpoint: The cRfD of 0.014 mg/ kg/ day was determined on the basis of the Combined Chronic Toxicity/ Carcinogenicity study in rats. This study provided the lowest NOAEL in the database ( most sensitive endpoint) and that will also provide the most protective limits for human effects. An uncertainty factor ( UF) of 100X ( 10 fold for interspecies extrapolation and 10 fold for intra species variability) was applied to the NOAEL of 1.4 mg/ kg/ day to derive the cRfD. The LOAEL of 83 mg/ kg/ day was based on decreased body weight and body weight gain in females. The FQPA SF of 1X is applicable for chronic dietary risk assessment. Therefore, the cPAD is 0.014 mg/ kg/ day.

Short and Intermediate Term Incidental Oral and inhalation Endpoints: Short and intermediate term incidental oral and inhalation endpoints are based on a 3 generation reproduction study in the rat. The LOAEL of 10 mg/ kg/ day was based on decreased body weight ( NOAEL = 2.0 mg/ kg/ day). A 3 generation reproduction study in the rat is selected for these scenarios because it is appropriate for the duration of exposures and population of concern. The level of concern for residential and occupational exposures is for MOEs < 100.

Long Term Inhalation Endpoints: Long term inhalation endpoints are based on the combined chronic toxicity/ carcinogenicity study in rats. The LOAEL was 83 mg/ kg/ day based on decreased body weight and body weight gain in females ( NOAEL 1.4 mg/ kg/ day). Since an oral NOAEL was selected for the inhalation exposure assessment, an inhalation absorption factor of 100% oral equivalent should be used. The level of concern for residential and occupational exposures is for MOEs < 100.

Dermal: Short, intermediate, and long term dermal risk assessments are not required for the following reason: the lack of dermal or systemic toxicity at 5000 mg/ kg ( 5X the limit dose) in a 21 day dermal toxicity study in rats which indicates poor dermal absorption. Page 16 of 28 Carcinogenicity: This chemical was previously classified by the HED RfD/ Peer Review Committee as Group E, evidence of non carcinogenicity for humans ( TXR No. 011277, 9/ 30/ 94). In accordance with current guidelines, terbacil is classified as not likely to be carcinogenic to humans based on the lack of evidence of carcinogenicity in a carcinogenicity study in mice and two combined chronic toxicity/ carcinogenicity studies in rats.

Table 6: Summary of Toxicological Dose and Endpoints for Terbacil Used in Human Risk Assessment Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary ( general population and Females 13+) An endpoint of concern attributable to a single dose for the general population and females 13+ was not identified.

Chronic Dietary ( All populations) NOAEL = 1.4 mg/ kg/ day UF = 100X cRfD = 0.014 mg/ kg/ day FQPA SF = 1X cPAD = cRfD ÷ FQOA SF = 0.014 mg/ kg/ day Combined Chronic Toxicity/ Carcinogenicity rat; LOAEL = 83 mg/ kg/ day, based on decreased body weight and body weight gain in females.

Short ( 1 30 days) and Intermediate ( 1 6 months) Term Incidental Oral NOAEL = 2.0 mg/ kg/ day level of concern ( LOC) for MOEs < 100 ( occupational and residential) 3 Gen Repro  rat; LOAEL = 10 mg/ kg/ day, based on decreased body weight Dermal ( Any Time Period) Quantification of dermal risk is not required; the lack of dermal or systemic toxicity at 5000 mg/ kg ( 5X the limit dose) in a 21 day dermal toxicity study in rats which indicates poor dermal absorption.

Short ( 1 30 days) and Intermediate ( 1 6 months) Term Inhalation oral NOAEL = 2.0 mg/ kg/ day ( inhalation absorption rate = 100% oral equivalent) LOC for MOEs < 100 ( occupational and residential) 3 Gen Repro  rat; LOAEL = 10 mg/ kg/ day, based on decreased body weight Long Term Inhalation (> 6 months) oral NOAEL = 1.4 mg/ kg/ day ( inhalation absorption rate = 100% oral equivalent) LOC for MOEs < 100 ( occupational and residential) Combined Chronic Toxicity/ Carcinogenicity rat; LOAEL = 83 mg/ kg/ day, based on decreased body weight and body weight gain in females.

Cancer Classification: Not likely to be carcinogenic to humans; cancer risk assessment is not required.

3.6 Endocrine Disruption EPA is required under the Federal Food Drug and Cosmetic Act ( FFDCA), as amended by FQPA, to develop a screening program to determine whether certain substances ( including all pesticide active and other ingredients) " may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee ( EDSTAC), EPA determined that there was scientific bases for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA has authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program ( EDSP). In the available toxicity studies on terbacil, there was no evidence of potential estrogen, androgen and/ or thyroid hormone mediated toxicity. Page 17 of 28 4.0 Public Health and Pesticide Epidemiology Data National Health and Nutrition Examination Survey ( NHANES): Terbacil was not measured in NHANES III ( 1988 1994) or in NHANES 99+ ( 1999 2002).

Agricultural Health Study: Terbacil was not among the top 50 chemicals assessed in Phase 1 of the Agricultural Health Study ( AHS). Terbacil had a low frequency of use in AHS Phase 2 with 13 subjects ( 6 NC and 7 Iowa) among 35,000 private applicators surveyed. Terbacil was reported as used on bluebeeries, strawberries and weed and brush control. It is not among the the top 83 chemical indicator variables developed in AHS Phase 2, due to the low frequency of use, so no additional information is available.

Other Pesticide Epidemiology Published Literature: There were no health related Pub Med citations for Terbacil.

5.0 Dietary Exposure/ Risk Characterization 5.1 Metabolism and Environmental Degradation Nature of the Residue  Plants: The petitioner has previously submitted and HED has reviewed alfalfa, blueberry, and sugarcane metabolism studies. Based on these data, HED concluded that the nature of the residue in plants is adequately understood and the residues of concern, for risk assessment and tolerance enforcement, are terbacil and metabolites A, B, and C ( Terbacil Reregistration Standard, 8 Mar 1989, R. Schmitt; D222891, D. Miller, 5 Dec 1996; HED RED, D. Miller, 18 Dec 1996).

Nature of the Residue  Livestock: The petitioner has previously submitted and HED has reviewed acceptable ruminant ( D190213, D. Miller, 9 Sep 1993) and poultry ( D192398, D. Miller, 28 Jul 1993) metabolism studies. Based on these data, HED concluded that the nature of the residues in livestock is adequately understood and the residues of concern, for risk assessment and tolerance enforcement, are terbacil and metabolites A, B, and C ( HED RED, D. Miller, 18 Dec 1996).

Nature of the Residue in Rotational Crops: A confined rotational crop study is not currently available. The HED RED ( D. Miller, 18 Dec 1996) stated that if the aerobic soil metabolism study ( MRID 42369901), which was being reviewed by the EFED, revealed no new metabolites other than those regulated in the primary crops, then a confined rotational crop study may not be required. The following information was gathered from the EFED RED ( D229773, J. Hetrick, 26 Jun 1997):

Terbacil is persistent under aerobic and anaerobic soil conditions ( t1/ 2= 235 to 653 days). Minor nonvolatile transformation products (< 10% of applied) are t butylurea and 3 t butyl 6 methyluracil. The major volatile transformation product is CO2. The reported laboratory degradation data indicate terbacil is persistent in terrestrial environments. Marginally acceptable field dissipation studies indicate terbacil, at 5 lbs ai/ acre, is persistent and mobile under actual use conditions. Field dissipation half lives in Delaware, Illinois, and California ranged from 204 to 252 days. The maximum depth of terbacil detection was 45 to 50 cm. Metabolites A ( maximum concentration 15 days after application ( 0.14 ppm)) and B ( maximum concentration 60 days after application ( 0.07 ppm)) were detected in the Page 18 of 28 field dissipation studies. The Chemistry Science Advisory Council ( ChemSAC) was consulted concerning the need for an additional confined rotational crop study. Based on the demonstrated persistence of terbacil in the aerobic and anaerobic soil metabolism studies ( half life = 235 653 days; EFED RED, D229773, J. Hetrick, 26 Jun 1997), the ChemSAC concluded that a confined rotational crop study is not necessary ( see ChemSAC minutes for 1 Feb 2006). Therefore, HED concludes that the residues of concern in rotational crops are terbacil, metabolite A, metabolite B, metabolite C, and 3 t butyl 6 methyluracil. Metabolites A, B, and C were included as these are residues of concern in the primary crops and may form in rotational crops via uptake and metabolism of parent. 3 t butyl 6 methyluracil was included as it was identified in the aerobic soil metabolism study. HED notes that 3 t butyl 6 methyluracil was identified at < 10% TRR; however, the aerobic soil metabolism study was conducted for only 1 year and the proposed registered plant back intervals ( PBIs) are 2 years ( i. e., concentration of 3 t butyl 6 methyluracil may be significant after 2 years; t butylurea was not included based on concentration and toxicological considerations).

Residues of concern in Drinking Water: The following information concerning the environmental fate of terbacil was taken from the EFED RED ( D229773, J. Hetrick, June 1997). Based on acceptable, supplemental, and ancillary environmental fate data, terbacil dissipation appears to be dependent on microbial mediated degradation, photodegradation in water, and movement into ground and surface waters. The relative importance of degradation and mobility in controlling terbacil dissipation under actual use conditions cannot be fully evaluated from the existing environmental fate data. However, the data indicate that terbacil is very persistent and potentially very mobile in terrestrial environments. Compounds with similar environmental fate behavior ( e. g., bromacil) have been detected in ground and surface waters.

Terbacil is stable to abiotic hydrolysis and slowly degrades through photolysis in natural and reference laboratory water samples ( t 1/ 2 = 29 to 54 days) and soil ( t 1/ 2 = 122 days). The photodegradation rate appears to be dramatically enhanced by the presence of some photosenitizers ( riboflavin and methylene blue). Major photodegradation transformation products (> 10% of applied) are ( 1) chloro 6 methyluracil, ( 2) 3 tert butyl 6 methyluracil, ( 3) 6 chloro 2,3 dihydro 3,3, 7 trimetyl 5H oxazolo ( 3,2 a) pyrimidine 5 one, ( 4) tert butyl 5 acetyl 5 hydroxyhydantoin, ( 5) 3 tert butyl 5 hydroxyhydantoin, and ( 6) 5 chloro 6 methyl( 3', 5') 5' chloro 6' methyl 5', 6' dihydro 6', 2 anhydro 3' tert butyluracilyluracil. Terbacil is persistent under aerobic and anaerobic soil conditions ( t 1/ 2 = 235 to 653 days). Minor nonvolatile transformation products are t butylurea ( aerobic and anaerobic soil metabolism), 3 t butyl 5 chloro 6 hydroxymethyuracil ( anaerobic soil metabolism), and 3 t butyl 6 methyuracil ( aerobic soil metabolism). The major volatile transformation product is CO 2 . The reported laboratory degradation data indicate terbacil is persistent in terrestrial environments.

Terbacil has a low sorption affinity to soil ( K ad = 0.39 to 1.3 ml/ g; K oc = 44 to 61 ml/ g). Therefore, terbacil is expected to be very mobile in soil. Soil column studies also indicate that terbacil and its transformation products can move through soil columns. Laboratory mobility studies indicate terbacil and its transformation products are potentially mobile in terrestrial environments.

Marginally acceptable field dissipation studies indicate terbacil, at 5 lbs ai/ acre, is persistent and Page 19 of 28 mobile under actual use conditions. Field dissipation half lives in Delaware, Illinois, and California ranged from 204 to 252 days. The maximum depth of terbacil detection was 45 to 50 cm. Ancillary field studies using plants as biological indicators also suggest that phytotoxic " terbacil residues" are persistent and mobile. Field dissipation studies confirm that terbacil is persistent and potentially mobile under actual use conditions.

Based on these data HED concluded that the residues of concern in drinking water are terbacil and the following photodegradates: ( 1) 5 chloro 6 methyluracil; ( 2) 3 tert butyl 6 methyluracil; and ( 3) 6 chloro 2,3 dihydro 3,3,7 trimethyl 5H oxazolo ( 3,2 a) pyrimidine 5 one.

Pesticide Metabolites and Degradates of Concern: Table 7 is a summary of the residues of concern in plants, livestock, rotational crops, and drinking water ( see preceding paragraphs for rationale):

Table 7: Residues for Tolerance Expression and Risk Assessment Matrix Residues included for Risk Assessment Residues included in the Tolerance Expression Plants1 terbacil and metabolites A, B, and C terbacil and metabolites A, B, and C Livestock terbacil and metabolites A, B, and C terbacil and metabolites A, B, and C Rotational Crops terbacil; metabolites A, B, and C; and 3 tert butyl 6 methyluracil terbacil; metabolites A, B, and C; and 3 tert butyl 6 methyluracil Drinking Water terbacil and the following photodegradates: ( 1) 5 chloro 6 methyluracil; ( 2) 3 tert butyl 6 methyluracil, and ( 3) 6 chloro 2,3 dihydro 3,3,7 trimethyl 5H oxazolo ( 3,2 a) pyrimidine 5 one not applicable Comparative Metabolic Profile: The proposed metabolic pathway for terbacil in rats involves the hydroxylation of the 6 methyl group to form metabolite A which is extensively conjugated to form the glucouronide and sulfate derivatives. Terbacil is also metabolized to the 5 hydroxy intermediate, which is further conjugated to form a sulfate derivative. The rat metabolism studies did not involve the formation of the oxazolo metabolites, 5 chloro 6 methyluracil, or 3 tert butyl 6 methyluracil ( residues of concern identified in plants, livestock, and/ or water). Based on the structure activity relationships, HED concludes that these compounds are not likely to be more toxic than parent ( see attachment 1 for structures).

5.2 Watermelon, Rotational Crop, and Drinking Water Residue Profile Watermelon Residue Profile: In support of the proposed application of terbacil to watermelon, the petitioner submitted a field trial study which presented the magnitude of terbacil ( limit of quantitation ( LOQ) = 0.50 ppm), metabolite A ( LOQ = 0.30 ppm), metabolite B ( LOQ = 0.10 ppm), and metabolite C ( LOQ = 0.10 ppm) residues in/ on watermelon following a single application at 0.248 0.297 lb ai/ acre ( 1.6 2.0x; PHI = 69 94 days). Combined residues of terbacil and metabolites A, B, and C in/ on the treated samples were < LOQ (< 1.0 ppm). Terbacil residues, per se, which were < LOQ were found in/ on many of the treated samples and ranged from < 0.001 0.091 ( n= 11) with one sample at 0.230 ppm ( no residues of metabolites A, B, or C were found in/ on any sample).

The high terbacil LOQ was due to residues at 0.134 ppm and 0.182 ppm in/ on two of the control Page 20 of 28 samples collected from the field trials. The study indicated that these may be treated samples mislabeled as untreated samples; however, no evidence supporting this claim was provided. Terbacil residues were found in/ on many of the remaining control samples at < 0.001 0.074 ppm (< 0.001 ppm ( n= 2) and 0.047 0.078 ppm ( n= 8)). If the 0.134 ppm and 0.182 ppm control samples are excluded and based on the residues in/ on the remaining control samples, a terbacil LOQ of at least 0.20 ppm would be established ( assumes LOQ = 3x the background). Assuming a terbacil LOQ of 0.20 ppm, terbacil residues in/ on the treated samples would be < LOQ for all excluding one, 0.230 ppm.

Based on the discussion from the previous paragraph, HED concludes that the data submitted in the watermelon field trial study are acceptable despite the exaggerated rate due to residues less than or slightly greater than the LOQ. HED generally allows for a 25% reduction in the suggested number of field trials when residues are < LOQ ( Table 5, OPPTS 860.1500). However, since the terbacil and metabolite A LOQs are high and since the label indicates that application after crop emergence is permitted ( all the currently available field trials were conducted post planting and prior to crop emergence), HED concludes this reduction is not appropriate and requests additional watermelon field trial, conducted with application after crop emergence, in Regions 3 ( n= 1), 5 ( n= 1), and 6 ( n= 1). Provided the petitioner agrees to submit these data and based on the currently available data, HED concludes that a tolerance of 1.0 ppm for the combined residues of terbacil and metaoblites A, B, and C in/ on watermelon is appropriate. A revised Section F is requested.

Rotational Crops Residue Profile: The residues of concern in rotational crops are terbacil; metabolites A, B, and C; and 3 tert butyl 6 methyluracil. Two field rotational crop studies and have been submitted and reviewed ( MRID 00011948  see EFED review, 23 July 1981; MRID 43221501  D206093, D. Miller, 31 Aug 1994). MRID 43221501 presented data concerning the magnitude of terbacil and metabolites A, B, and C in/ on beet ( root and tops), wheat, and lettuce following a bare soil application at 5.0 lb ai/ acre ( 33x the watermelon rate) and a 2 year plantback interval ( PBI). Due to phytotoxicity, neither immature nor mature wheat and lettuce plants could be harvested for residue analysis. Phytotoxicity was also observed for beets with severe reduction in harvest yield noted and only small samples of immature and mature beets harvested. Terbacil residues were 0.19 ppm in/ on immature beet ( whole plant), 0.07 ppm in/ on mature beet top, and < 0.05 ppm in/ on mature beet root. Metabolites A, B, and C were < 0.05 ppm in/ on all mature and immature beet samples. MRID 00011948 presented data concerning the magnitude of terbacil and metabolite A in/ on beet ( root and tops), sunflower ( seed), and cabbage following ten annual applications of terbacil at 1.0 lb ai/ acre ( 10 month PBI; silt loam soil; 6.7x the watermelon rate) and three annual applications of terbacil at 1.0 2.0 lb ai/ acre ( 2 year PBI; muck soil; 13.3x the watermelon rate; 2.0 lb ai/ acre the 1st year and 1.0 lb ai/ acre for the 2nd and 3rd years). Residues of terbacil and metabolite A were < LOQ in/ on all samples excluding cabbage grown in muck ( 2 year PBI) where terbacil residues of 0.18 ppm were found.

Based on the watermelon application rate and the results of the currently available field trial studies ( 6.7 33x the watermelon application rate; terbacil and metabolite A residues of # 0.19 ppm), HED concludes that residues in/ on crops rotated into watermelon fields which were treated with terbacil is unlikely. Therefore, additional field rotational crop studies conducted at the maximum proposed/ registered application rate and monitoring for the residues of concern in rotational crops are unnecessary for the current petition. However, HED notes that future Page 21 of 28 petitions may require additional field rotational crop studies ( see ChemSAC minutes for 1 Feb 2006). Currently, there are no rotational crop tolerances; however, based on the available field rotational crop data and the application rates for the currently registered crops, residues in/ on crops rotated into alfalfa ( 2 x 1.2 lb ai/ acre), mint ( 2 x 1.2 lb ai/ acre), and sugar cane ( 1 x 3.2 lb ai/ acre) fields which were treated with terbacil are possible. Based on the available field rotational crop data, the dietary analysis assumed a residue of 1.0 ppm for cereal grains and soybean ( these crops are commonly rotated into alfalfa, mint, and sugarcane fields; D212427, D. Miller, 12 Dec 1996 and communication from B. Schneider). Based on the tolerances for the primary crops ( 0.1 2.0 ppm), HED anticipates that the 1.0 ppm residue estimate is conservative. HED notes that the assessment assumes that only cereal grains and soybean are rotated into alfalfa, sugar cane, and mint fields while the registered application scenario for these crops permits the rotation of any crop.

Analytical Methodology: There are currently two terbacil enforcement methods in the Pesticide Analytical Manual ( PAM; Vol. II). The HED RED ( D. Miller, 18 Dec 1996) concluded that Method I is unacceptable as it does not include instructions for the quantitation of metabolites A, B, and C and Method II is unacceptable as it uses a microcoulometric detector. The HED RED went on to say that an adequate gas chromatograph/ nitrogen phosphorus detector ( GC/ NPD) method, which is a modification of Method II in PAM ( Vol. II), may be an appropriate enforcement method and requested that the petitioner submit this procedure to HED for a petition method validation ( PMV; since the procedure is similar to Method II, an independent laboratory validation ( ILV) was deemed unnecessary). The petitioner did not submit a separate study with the analytical procedure for this method. However, the watermelon field trial study employed the method in question and this study included a copy of the analytical procedure as an attachment. This information was forwarded to the ACL of BEAD for PMV ( D324601, T. Bloem, 21 Dec 2005). A successful PMV is needed before this method may be used for enforcement.

Multiresidue Methods: Data have been submitted pertaining to the analytical behavior of terbacil and its regulated metabolites through FDA Multiresidue Protocols and these data have been forwarded to FDA for inclusion in PAM ( Vol. I, Appendix I). The registrant has submitted the results of FDA Multiresidue Protocol C to the Agency ( Protocols A, B, and E are not applicable) which demonstrates that terbacil and its metabolites yield acceptable results when tested under the specified GLC conditions. Results from Protocol D, however, were not submitted, and the registrant is required to use this method to test an appropriate commodity and submit the results for terbacil and its regulated metabolites for inclusion in PAM ( HED RED, D. Miller, 18 Dec 1996). These data have not been submitted.

International Residue Limits: There are no Codex, Canadian, or Mexican maximum residue limits ( MRLs) in/ on the requested crops. Page 22 of 28 Drinking Water Residue Profile: EFED provided surface ( PRZM/ EXAMS) and ground water ( SCI GROW) EECs for terbacil and its metabolites of concern ( D313755, I. Abdel Saheb, 20 Dec 2005). Several scenarios were run with sugarcane ( 1 x 3.0 lb ai/ acre; highest registered/ proposed application rate) yielding the highest EECs. The PRZM/ EXAMS model assumed that a percent cropped area of 87%. Table 8 is a summary the drinking water estimates.

Table 8: Estimated concentrations of Terbacil and Degradates of Concern in Surface and Ground Water Crop EECs (: g/ L)

Acute One in 10 year annual mean Surface water 123 25.4 Ground Water 111 5.3 Dietary Exposure and Risk Chronic dietary risk assessments were conducted using the DEEM FCID   ( ver. 2.03) model which incorporates consumption data from the USDA CSFII ( 1994 1996 and 1998). The chronic dietary analysis incorporated tolerance level residues, 100% crop treated, and DEEM ( ver 7.81) default processing factors for all registered/ proposed crops. The SCI GROW modeled water estimate was assumed for all water sources ( direct and indirect). Although rotational crop tolerances are not currently established, based on the available field rotational crop data and the application rates, residues in/ on crops rotated into alfalfa, sugarcane, and mint fields which were treated with terbacil are possible ( alfalfa, sugarcane, and mint are registered crops). Therefore, the analysis incorporated a conservative residue estimates for cereal grains and soybean ( crops which are commonly rotated with alfalfa, sugarcane, and mint). The chronic dietary exposure estimates were # 99% the cPAD and are therefore less than HED's level of concern ( all infants < 1 year were the most highly exposed population subgroup). Table 9 is a summary of the chronic dietary exposure analyses ( acute and cancer exposure assessments are unnecessary).

HED notes that the assessment assumes that only cereal grains and soybean are rotated into alfalfa, sugar cane, and mint fields while the registered application scenario for these crops permits the rotation of any crop ( this assumption is based on cultural practices). When the residue estimates used to generate the dietary exposure estimates are taken in total ( SCI GROW drinking water estimates; tolerance level residue and 100% crop treated for all registered/ proposed crops), HED concludes that exposure to terbacil is likely to be significantly lower than the estimates provided in this document.

Table 9: Summary of Chronic Dietary Exposure and Risk for Terbacil ( drinking water included)

Population Subgroup Chronic cPAD ( mg/ kg/ day) Exposure ( mg/ kg/ day) % aPAD General U. S. Population 0.01 0.005584 40 All Infants (< 1 year old) 0.013823 99 Children 1 2 years old 0.013161 94 Children 3 5 years old 0.011751 84 Children 6 12 years old 0.007500 54 Youth 13 19 years old 0.004892 35 Adults 20 49 years old 0.004650 33 Adults 50+ years old 0.004184 30 Table 9: Summary of Chronic Dietary Exposure and Risk for Terbacil ( drinking water included)

Population Subgroup Chronic cPAD ( mg/ kg/ day) Exposure ( mg/ kg/ day) % aPAD Page 23 of 28 Females 13 49 years old 0.004510 32 6.0 Residential ( non occupational Exposure/ Risk Characterization There are no registered/ proposed application scenarios that are expected to result in residential exposure. HED notes that spray drift is always a potential source of exposure to residents nearby to spraying operations. This is particularly the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground application. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices. The Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/ labeling. The Agency has completed its evaluation of the new data base submitted by the Spray Drift Task Force, a membership of U. S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast, and ground hydraulic methods. After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce off target drift and risks associated with aerial as well as other application types where appropriate.

7.0 Aggregate Risk Assessments and Risk Characterization Since there are no registered/ proposed uses which result in residential exposures, only chronic aggregate exposure assessments, considering exposure from food and water, is required ( acute and cancer assessments are unnecessary). Since the dietary exposure analysis included the drinking water estimates, the discussion and exposure estimates presented in Section 5.3 represent aggregate chronic risk assessment.

8.0 Cumulative Unlike other pesticides for which EPA has followed a cumulative risk approach based on a mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to terbacil and any other substances and terbacil does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that terbacil has a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's website at http:// www. epa. gov/ pesticides/ cumulative/. Page 24 of 28 9.0 Occupational Exposure/ Risk Pathway The petitioner is proposing application of Dupont   Sinbar ® Herbicide ( 80WP; EPA Reg. No. 352 317) to watermelon. Table 2 is a summary of the proposed application scenario.

9.1 Handler Risk Based upon the proposed use pattern and the lack of dermal endpoints ( see previous section), HED believes occupational pesticide handlers ( i. e., mixers, loaders and applicators) will be exposed to only short term ( 1  30 days) inhalation exposures. Treatment blocks ( number of acres) are relatively small compared to typical field crops such as cotton, corn, soybeans or wheat. Due to the methods of application, it is likely that handlers will be private, grower ( noncommercial handlers. The most highly exposed handlers are expected to be a mixer/ loader using open pour of WPs and an applicator using ground boom equipment.

Chemical specific data were not available with which to assess pesticide handler exposure. Therefore surrogate data from studies in the Pesticide Handler Exposure Database Version 1.1 ( August 1998) PHED SURROGATE EXPOSURE GUIDE were used to estimate mixer/ loader and applicator exposure. It is HED policy to assess handler exposure and risk using " baseline" PPE which is comprised of long sleeved shirt, long pants, and shoes plus socks and if necessary to assess " baseline" plus the use of protective gloves or other PPE as might be necessary or appropriate.

In some cases, HED recognizes that the same individual may perform all three tasks, i. e., mix, load and apply a pesticide material. The available exposure data for combined mixer/ loader/ applicator scenarios are limited in comparison to the monitoring of these two activities separately. These exposure scenarios are outlined in the PHED Surrogate Exposure Guide ( August 1998). HED has adopted a methodology to present the exposure and risk estimates separately for the job functions in some scenarios and to present them as combined in other cases. Most exposure scenarios for hand held equipment ( such as hand wands, backpack sprayers, and push type granular spreaders) are assessed as a combined job function. With these types of hand held operations, all handling activities are assumed to be effected by the same individual. The available monitoring data support this and HED presents them in this way. Conversely, for equipment types such as fixed wing aircraft, groundboom tractors, or air blast sprayers, the applicator exposures are assessed and presented separately from those of the mixers and loaders. By separating the two job functions, HED determines the most appropriate levels of PPE for each aspect of the job without requiring the applicator to wear unnecessary PPE that may be required for a mixer/ loader ( e. g., chemical resistant gloves may only be necessary during the pouring of a liquid formulation).

A MOE of 100 is adequate to protect occupational pesticide handlers. Since the MOE's are > 100, the proposed use does not exceed HED's level of concern. Table 10 is a summary of exposures and risks to occupational pesticide handlers. Page 25 of 28 Table 10: Estimated Handler Exposure and Risk from the Use of Terbacil on Watermelon Unit Exposure1 ( mg ai/ lb handled) Applic. Rate2 Units Treated3 Per Day Average Daily Dose4 mg ai/ kg bw/ day MOE5 Mixer/ Loader  WP  Open Pour Inhal 0.0434 HC 0.15 lb ai/ acre 200 A Inhal 0.019 108 Applicator  Ground boom  Open Cab Inhal 0.00074 HC 0.15 lb ai/ acre 200 A Inhal 0.00032 6,300 1 Unit Exposures are taken from " PHED SURROGATE EXPOSURE GUIDE", Estimates of Worker Exposure from The Pesticide Handler Exposure Database Version 1.1, August 1998. Inhal. = Inhalation. Units = mg a. i./ pound of active ingredient handled. Data Confidence: LC = Low Confidence, MC = Medium Confidence, HC = High Confidence. 2 Applic. Rate. = Taken from supplemental label and IR 4 submission.. 3 Units Treated are taken from " Standard Values for Daily Acres Treated in Agriculture"; SOP No. 9.1. Science Advisory Council for Exposure; Revised 5 July 2000; 4 Average Daily Dose = Unit Exposure x Applic. Rate x Units Treated ÷ Body Weight ( 70 kg). 5 MOE = NOAEL ÷ ADD; NOAEL = 2.0 mg ai/ kg bw/ day 9.1 Postapplication Risk Typically, it is possible for agricultural workers to experience post application exposures to dislodgeable pesticide residues. In this case, there are no dermal toxicological endpoints identified. HED believes that post application inhalation exposures are negligible. There is a 12 hour restricted entry interval ( REI) for this product. It is expected that there is no volatility as the spray is essentially dry after 12 hours. The product is a WP versus a liquid formulation thereby further reducing the possibility of significant inhalation exposure. The proposed use does not exceed HED's level of concern.

10.0 Data Needs and Label Requirements 10.1 Toxicology Cnone 10.2 Residue Chemistry CRevised Section F CPMV of the plant and livestock enforcement methods CFDA multiresidue testing of terbacil and its metabolites A, B, and C through protocol D Cadditional watermelon field trial, conducted with application after crop emergence, in Regions 3 ( n= 1), 5 ( n= 1), and 6 ( n= 1)

10.3 Occupational/ Residential Exposure Cnone RDI: RAB1 ( 15 Feb 2006) T. Bloem: 806R: CM# 2:( 703) 605 0217: 7590C Page 26 of 28 Attachment 1: Chemical Structures Page 27 of 28 N HN O C( CH3) 3 O Cl H3C N HN O C( CH3) 3 O Cl HOH2C N N O Cl HOH2C O H3C CH3 N N O Cl H3C O H3C CH3 N HN O C( CH3) 3 O H H3C ( H3C) C N NH2 H O N HN O C( CH3) 3 O Cl OH2C gluc Attachment 1: Chemical Structures Name Structure terbacil 3 tert butyl 5 chloro 6 methyluracil 5 chloro 3( 1,1 dimethylethyl) 6 methyl 2,4( 1H, 3H) pyrimidinedi one metabolite A ( also called DF4)

3 tert butyl 5 chloro 6 hydroxymethyluracil metabolite B 6 chloro 2,3 dihydro 7 hydroxymethyl 3,3 dimethyl 5Hoxazolo ( 3,2 a) pyrimidin 5 one metabolite C 6 chloro 2,3 dihydro 3,3,7 trimethyl 5H oxazolo ( 3,2 a) pyrimidin 5 one 3 t butyl 6 methyluracil t butylurea DF1 Name Structure Page 28 of 28 N HN O C( CH3) 3 O HO3SO H3C N HN O C( CH3) 3 O Cl HO3SOH2C EF2 EF1/ EF3


			  UNITED STATES OF AMERICA

		        DEPARTMENT OF TRANSPORTATION

			  OFFICE OF THE SECRETARY

			          WASHINGTON, D.C.

Issued by the Department of Transportation on April 22, 2003

NOTICE OF ACTION TAKEN -- DOCKET OST 1997-2651

________________________________________________________________________
________________________________________________________

This serves as notice to the public of the action described below, taken
by the Department official indicated (no additional confirming order
will be issued in this matter).

Applicant:  SERVICIOS AERONAUTICOS Z, S.A. de C.V.
                        Date Filed: March 26, 2003

Relief requested:  Exemption from 49 USC section 41301 to permit the
applicant to continue to conduct passenger charter operations between
Mexico and the United States, and other passenger charter operations in
accordance with 14 CFR Part 212, using small equipment.

If renewal, date and citation of last action:  April 22, 2002, in this
Docket.

Applicant representative(s):  Daniel Elizondo,<PHONE_NUMBER>         DOT
analyst:  Allen F. Brown,<PHONE_NUMBER>

Responsive pleadings:  None.

	DISPOSITION

Action:  Approved.
         Action date:  April 22, 2003

Effective dates of authority granted:  April 22, 2003, through April 22,
2004.

Basis for approval (bilateral agreement/reciprocity):  United
States-Mexico Air Transport Services Agreement of August 15, 1960, as
amended and extended (Agreement).

Except to the extent exempted/waived, this authority is subject to the
terms, conditions, and limitations indicated:  Standard exemption
conditions.

Special conditions/Partial grant/Denial basis/Remarks:  In the conduct
of these operations, the carrier must adhere to all applicable
provisions of the U.S.-Mexico Agreement.  In the conduct of these
operations, the carrier may only use aircraft capable of carrying no
more than 60 passengers and having a maximum payload capacity of no more
than 18,000 pounds (small equipment).  The above grant includes
authority to conduct Third and Fourth Freedom charter operations.  While
we have subjected, consistent with the provisions of the Agreement,
Mexican carriers conducting charter operations with large aircraft to
prior approval or submission of notice for their Third and Fourth
Freedom charters, we determined that any such requirement was not
necessary on public interest grounds in this case, since the carrier
will be conducting these operations solely with small aircraft.  (Other
charter operations to/from the United States under this authority,
however, are subject to prior approval under 14 CFR Part 212.)  Further,
we are continuing to allow Mexican carriers conducting passenger
charters using small equipment to make stopovers in the United States in
the conduct of such operations.

Action taken by:   Paul L. Gretch, Director

		      Office of International Aviation

________________________________________________________________________
________________________________________________________

Under authority assigned by the Department in its regulations, 14 CFR
Part 385, we found that (1) our action was consistent with Department
policy; (2) the applicant was qualified to perform its proposed
operations; (3) grant of the authority was consistent with the public
interest; and (4) grant of the authority would not constitute a major
regulatory action under the Energy Policy and Conservation Act of 1975.
To the extent not granted/deferred/dismissed, we denied all requests in
the referenced Docket.  We may amend, modify, or revoke the authority
granted in this Notice at any time without hearing at our discretion.

Persons entitled to petition the Department for review of the action set
forth in this Notice under the Department’s regulations, 14 CFR
§385.30, may file their petitions within seven (7) days after the date
of issuance of this Notice.  This action was effective when taken, and
the filing of a petition for review will not alter such
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