Document ID: EPA-HQ-OPP-2020-0232-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2020-11-17T05:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: [Maryam Muhammad (Acting PM); 703-308-9354]

[Bayer Crop Science]

[9E8786]

	EPA has received a pesticide petition (9E8786) from [Bayer CropScience] 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.
   
   	1. by establishing the tolerances for residues of

	[Tebuconazole] in or on the raw agricultural commodity [Rice, grain] at [15.0] 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  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

	1. Plant metabolism. [The nature of the residue in plants and animals is adequately understood.  The residue of concern is the parent compound only, as specified in 40 CFR 180.474.]

	2. Analytical method. [An enforcement method for plant commodities has been validated on various commodities.  It has undergone successful EPA validation and has been submitted for inclusion in PAM II.  The animal method has also been approved as an adequate enforcement method.  The analytical method for crops used for the studies referenced with this submission involves solvent extraction, filtration and addition of an isotopically labeled internal standard.  Quantitation was by high performance liquid chromatography/triple stage quadrupole mass spectrometry (LC/MS/MS).]
	3. Magnitude of residues. [Five crop field trial studies, comprised of 31 trials, were conducted at locations in Thailand, Vietnam, India, Brazil and the U.S. to measure the magnitude of tebuconazole residues in/on paddy rice.  Four different formulations were used with four different use patterns.

Folicur 430 SC and Nativo(R) 75 WG:

In one study (RAHWN010), ten trials were conducted in Thailand (6), Vietnam (2) and India (2) with one control plot and 2 treated plots per trial.  The first treated plot received three broadcast foliar spray applications of Folicur 430 SC, a suspension concentrate (SC) formulation containing 430 g/L of tebuconazole at a treatment rate of 0.192 lbs tebuconazole/A/application (215 g/ha).  The spray interval ranged from 10 to 15 days and whole grain samples were collected at target PHI's of 28 and 35-days. The second treated plot received two broadcast foliar spray applications of Nativo(R) 75 WG, a water-dispersible granule formulation (WG) containing 500 g/kg tebuconazole and 250 g/kg trifloxystrobin at a treatment rate of 0.134 lbs tebuconazole/A/application (151 g/ha) and with a 6 to 8-day spray interval.  Whole grain samples were collected at target PHI's of 21 and 28-days. 

In a second study (RAHW0005), four additional trials were conducted in the United States with Folicur 430 SC and Nativo(R) 75 WG and a similar use pattern.  Each trial had one control plot and 2 treated plots.  The first treated plot received three broadcast foliar spray applications of Folicur 430 SC at a treatment rate of 0.192 lbs tebuconazole/A/application (215 g/ha).  The spray interval ranged from 13 to 14 days and whole grain samples were collected at target PHI's of 21, 28 and 35-days. The second treated plot received two broadcast foliar spray applications of Nativo(R) 75 WG at a treatment rate of 0.134 lbs tebuconazole/A/application (151 g/ha) and with a 6 to 8-day spray interval.  Whole grain samples were collected at target PHI's of 7, 14, 21 and 28-days.

Luna Experience 400 SC:

In a third study (RAGMP189), ten trials were conducted in Thailand (6), Vietnam (2) and India (2) with Luna Experience 400 SC, a suspension concentrate containing 200 g/L fluopyram and 200 g/L tebuconazole.  Each trial included one control plot and one treated plot.  The treated plot received 2 broadcast foliar spray applications of Luna Experience 400 SC at a treatment rate of 0.10 lbs tebuconazole/A/application (110 g/ha).  The spray interval ranged from 8 to 12 days and whole grain samples were collected at target PHI's of 28 and 35 days.

In a fourth study (RAGMN176), two additional trials were conducted in the United States with Luna Experience SC 400.  Each trial included one control plot and one treated plot with the treated plot receiving 2 broadcast foliar spray applications of Luna Experience 400 SC at a treatment rate of 0.10 lbs tebuconazole/A/application (110 g/ha).  The spray interval ranged from 9 to 10 days and whole grain samples were collected at target PHI's of 28 and 35 days.
Nativo(R):

In a fifth study (F15-060), five trials were conducted in/on rice in Brazil in which Nativo(R), a concentrated suspension containing 200 g/L tebuconazole and 100 g/L trifloxystrobin, was applied by broadcast foliar spray.  Each trial included one control plot and one treated plot.  The treated plot received 3 foliar spray applications of Nativo(R) at a treatment rate of 0.179 lbs tebuconazole/A/application (200 g/ha) and a spray interval of 10 days.  Whole grain rice samples were collected at PHIs of 15, 25, 35 and 45 days.

Processing:

Two rice processing trials (RAGMN175) were conducted in Thailand with Luna, plots were treated twice with the first application at a treatment rate of 330 g tebuconazole/ha (0.30 lbs tebuconazole/A) followed by a second application at a treatment rate of 350 g tebuconazole/ha (0.32 lbs tebuconazole/A).  A comparison of the residues in the raw agricultural commodity (RAC) with those in each processed fraction resulted in average processing factors of 0.24X, 0.081X, 2.2X, 0.88X and 0.030X for brown rice, polished rice, hulls, bran and cooked rice, respectively.]

B. Toxicological Profile

	1. Acute toxicity.  [Tebuconazole exhibits moderate toxicity. The rat acute oral LD50 = 3,933 milligram/kilogram (mg/kg) (category III); the rabbit acute dermal LD50 > 5,000 mg/kg (category IV); and the rat acute inhalation LC50 > 0.371 mg/L (category II). Technical tebuconazole is slightly irritating to the eye (category III) and is not a skin irritant (category IV) in rabbits. Tebuconazole is not a dermal sensitizer.]

	2. Genotoxicty. [A battery of genotoxicity studies (Ames Assay, CHO-HGPRT mutation assay, mouse micronucleus assay, sister chromatid exchange assay in CHO cells, in vitro cytogenetics assay in human lymphocytes, and unscheduled DNA synthesis assay with rat hepatocytes) provide no evidence of genotoxicity.]

	3. Reproductive and developmental toxicity.  [Developmental toxicity studies in rats, mice and rabbits showed developmental effects at similar dose levels concomitant with little to no maternal toxicity.  In a two-generation reproduction study in rats, adverse effects on offspring were manifested only as decreased pup body weight; the parental and offspring NOAEL is 15 mg/kg/day.  In a developmental neurotoxicity study, decreased absolute brain weight, morphometric measurements, and motor activity were seen in offspring at the LOAEL of 8.8 mg/kg/day.]

	4. Subchronic toxicity.  [The liver, adrenals and the hematopoetic system were identified as target organs in 90-day oral feeding studies in rats and/or dogs.  In addition, ocular lesions were observed in dogs.  NOAELs were 34.8 and 10.8 mg/kg/day in male and females rats, respectively, and 73.4 and 73.7 mg/kg/day in male and female dogs respectively.  In a 21-day dermal toxicity study in rabbits exposed 5 days a week, no dermal or systemic toxicity was observed up to the limit dose of 1,000 mg/kg/day.  In a 21-day inhalation study in rats, a NOAEL of 0.0106 mg/L/day was established based on clinical signs and induction of liver microsomal enzymes.]

	5. Chronic toxicity. [The liver, adrenals and the hematopoetic system were also identified as target organs in chronic feeding studies in rats (2 years) and dogs (1 year).  In addition, ocular lesions were observed in dogs similar to those observed after 90 days of exposure.  No evidence of carcinogenicity was observed in rats.  In  mice after 91 weeks of exposure, a dose-related trend in hepatocellular tumors was observed in both sexes.]
	
	6. Animal metabolism. [Rats were gavaged with 1 or 20 mg/kg radio-labeled technical tebuconazole. 98.1% of the oral dose was absorbed. Within 72 hours of dosing, over 87% of the dose was excreted in urine and feces. At sacrifice (72 hours post dosing), total residue (-GI tract) amounted to 0.63% of the dose. A total of 10 compounds were identified in the excreta. A large fraction of the identified metabolites corresponded to successive oxidations steps of a methyl group of the test material. At 20 mg/kg, changes in detoxification patterns may be occurring.]

	7. Metabolite toxicology. [1,2,4-triazole, triazole alanine and triazole acetic acid are potential residues of concern for all triazole fungicides, and are considered toxicologically different from tebuconazole.  However, exposure to these degradates is assessed independently as part of the triazole aggregate risk assessment, and does not need to be considered in the risk assessment for tebuconazole.]

	8. Endocrine disruption. [Tebuconazole was one of the chemicals included in List 1 of the EPA Endocrine Disruptor Screening Program (EDSP). The EDSP weight of evidence review concluded that tebuconazole showed the potential to alter the steroidogenesis pathway, which may result in endocrine-related effects in the estrogen and androgen pathways. There is no indication of an interaction with the thyroid pathway.]

C. Aggregate Exposure

	1. Dietary exposure. [The proposed import tolerance use of tebuconazole on rice grain has minor effects on the previous dietary aggregate risk assessment conducted for all existing registered uses (EPA, D443689, November 2, 2017).  Residues for rice a blended commodity were based on average residues from field trial studies on rice.  Processing factors were used for rice, polished; rice, brown; and rice cooked based on processing study (RAGMN175).  Dietary assessments, using the DEEM FCID Version 4.02 software, evaluated the potential risks due to chronic and acute dietary exposure of the U.S. population and selected population subgroups to residues of tebuconazole.  Consumption data used in this program were based on the most recent NHANES WWEIA 2005-2010.

The EPA's January 31, 2013 Tebuconazole Human Health Risk Assessment used the LOAEL of 8.8 mg/kg/day from a tebuconazole rat developmental neurotoxicity study and an uncertainty factor of 300 to establish the acute and chronic population adjusted doses (aPAD and cPAD, respectively) at 0.029 mg/kg/day. 

Results of this assessment show that no harm to the overall U.S. population or any population subgroup will result from the use of tebuconazole on currently registered uses when incorporating the additional residue results.]

	i. Food. [A slightly refined dietary assessment including all of the current and pending uses of tebuconazole showed that the most highly exposed population subgroup for food only for the acute assessment was children 1-2 yrs. old with an exposure equal to 52% of the aPAD.  The U.S. total population had an exposure for food only equal to 30% of the aPAD.  The chronic analysis for food only showed that the most highly exposed population subgroup was children 1-2 yrs. old with an exposure equal to 10% of the cPAD.  The total U.S. population had a chronic exposure equal to 4% of the cPAD.  These exposure estimates are below EPA's level of concern.]

	ii. Drinking water. [The proposed import tolerance use of tebuconazole on rice grain will not change the estimated drinking water concentrations.  Acute and chronic exposure estimates for combined food plus water intake are below EPA's level of concern.  For the acute assessment, using a distribution of estimated daily surface water concentrations from Florida turf scenario showed that the most highly exposed population subgroup for food and water was infants (<1 yrs. old) with an exposure equal to 78% of the aPAD.  The U.S. total population had an exposure for food and water equal to 44% of the aPAD.  For the chronic assessment, using a chronic drinking water level of 69 ppb showed that the most highly exposed population subgroup was infants (<1 yrs. old) with an exposure equal to 27% of the cPAD.  The total U.S. population had a chronic exposure equal to 9% of the cPAD.]
	
	2. Non-dietary exposure. [Tebuconazole currently registered for use on the following residential non-food sites: residential application to roses, flowers, trees and shrubs; the formulation of wood-based composite products; wood products for in-ground contact; plastics; glues and adhesives.  EPA in their April 18 2008 Human Health Risk Assessment assessed residential handler, post-application and other exposures (drift etc.) to homeowners. EPA concluded that exposures to homeowners do not exceed the level of concern]

D. Cumulative Effects. [Tebuconazole is a member of the triazole class of systemic fungicides.  There is currently no evidence to indicate that triazole-derivative fungicides share common mechanisms of toxicity and EPA is not following a cumulative risk approach based on a common mechanism of toxicity for the triazole derivative fungicides (from December 7, 2015 Human Health Scoping Document in Support of Registration Review).

Therefore, for this tolerance petition, it is assumed that tebuconazole does not have a common mechanism of toxicity with other substances and only the potential risks of tebuconazole in its aggregate exposure are considered.  A May 1, 2013 dietary (food + water) risk assessment performed by EPA on the primary common metabolites of triazole pesticides (1,2,4-triazole and its TA and TAA conjugates) shows acute and chronic dietary exposure estimates as being below the level of concern for all population subgroups, including infants and children, indicating no dietary exposure considerations for common triazole metabolites of prothioconazole.]

E. Safety Determination

	1. U.S. population. [Based on the information supplied under Aggregate Exposure describe above, there is reasonable certainty that exposure from tebuconazole will not result in harm to the U.S. population.]

	2. Infants and children. [Based on the information supplied under Aggregate Exposure describe above, there is reasonable certainty that exposure from tebuconazole will not result in harm to infants and children.]

F. International Tolerances

[International tolerances/MRLs for tebuconazole have been established for various crops.  EU and Brazil MRLs are 1.0 ppm and India, Thailand and Vietnam MRLs are 1.5 ppm for rice grain.]