Sipcam Agro USA, Inc. and Isagro S.p.A. Pesticide Tolerance. FINAL RULE.

• Human Health Aggregate Risk Assessment for Triazole-derivative Fungicide Compounds (1,2,4-Triazole, Triazole Alanine, Triazole Acetic Acid). US EPA, February 7, 2006.

Hazard Characterization (Page 13)
1,2,4-triazole (free triazole) is a metabolite common to a number of triazole-derivative pesticides, and is found in both mammalian (rat) and plant metabolism studies. Although for most pesticides, mammals convert only a small proportion to free triazole (less than 25%), two compounds (tetraconazole and flusilazole) demonstrate relatively high conversion (68-77%) in rat metabolism studies. As a plant metabolite, and given the wide use of triazole-derivative pesticides (used as fungicides on many crops as well as on turf) free triazole is found in a variety of food commodities, including animal byproducts. 1,2,4-triazole appears to be relatively stable in the environment, and may be found in rotational crops as well as in water. ...

Documents in the Federal Register Docket:

Tetraconazole: Human-Health Risk Assessment for Proposed Uses on Soybean, Sugar Beet, Peanut, Pecan, and Turf. January 26, 2007 - 105 pages
Docket #: EPA-HQ-OPP-2006-0576-0010

Tetraconazole. Dietary Exposure and Risk Assessment. Application of Tetraconazole to Pecan, Sugar Beet, and Soybean. January 23, 2007 - 39 pages
Docket #: EPA-HQ-OPP-2006-0576-0011

Notice of Filing Sipcam Agro USA (PP#9F6023 and PP#6F7084) Undated - 9 pages
Docket #: EPA-HQ-OPP-2006-0576-0004

Notice of Filing Sipcam Agro USA (PP#9F5066) - Undated - 6 pages
Docket #: EPA-HQ-OPP-2006-0576-0005

Notice of Filing PP#576971 Isagro - Undated - 6 pages
Docket #: EPA-HQ-OPP-2006-0576-0007

Projected Percent Crop Treated for the Fungicide Tetraconazole - November 29, 2006 - 9 pages
Docket #: EPA-HQ-OPP-2006-0576-0009

Sipcam Agro USA, Inc. Pesticide petitions.

Pesticide Petition PP 6F7084.
in or on the food commodity
-- pecan at 0.05 ppm.

Pesticide Petition PP 9F6023.
in or on the food commodity
-- peanut, nutmeat at 0.05 ppm
-- peanut, refined oil at 0.15 ppm.

Pesticide Petition PP 9F5066.
in or on the food commodities
-- sugarbeet roots at 0.05 ppm
-- sugarbeet top at 3.0
-- sugarbeet dried pulp at 0.15 ppm
-- sugarbeet molasses at 0.15 ppm
-- meat of cattle, goat, horse and sheep at 0.05 ppm
-- liver of cattle, goat, horse and sheep at 4.0 ppm
-- fat of cattle, goat, horse and sheep at 0.30 ppm
-- meat byproducts, except liver, of cattle, goat, horse and sheep at 0.10 ppm
-- milk at 0.05 ppm.

Pesticide Product Registrations; Conditional Approval.

This notice announces Agency approval of applications submitted by Sipcam Agro, USA Inc. to conditionally register the pesticide products, Tetraconazole Technical, EPA Registration Number 60063-11 and Eminent 125 SL Fungicide, EPA Registration Number 60063-12, containing a new active ingredient not included in any previously registered products pursuant to the provisions of section 3(c)(7)(C) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended.

EPA issued a notice, published in the Federal Register of October 20, 1999 which announced that Sipcam Agro, USA Inc., 70 Mansell Court, Suite 230, Roswell, GA 30076 submitted an application to register the following two pesticide products:
1. Tetraconazole Technical, (EPA File Symbol: 60063-RR). Active ingredient: Tetraconazole: at 97.0%. The application for the product Tetraconazole Technical was approved for manufacturing or formulating purposes on April 14, 2005, to use for formulation into end-use products for use on sugar beets (EPA Registration Number 60063-11).
2. Eminent 125SL Fungicide, (EPA File Symbol: 60063-RE). Active ingredient: Tetraconazole: at 11.6%. The application for the product Eminent 125SL was approved on April 14, 2005 for the control of Cercospora leaf spot and powdery mildew disease of sugar beets (EPA Registration Number 60063-12).

The Agency has considered the available data on the risks associated with the proposed use of tetraconazole, and information on social, economic, and environmental benefits to be derived from such use. Specifically, the Agency has considered the nature and its pattern of use, application methods and rates, and level and extent of potential exposure. Based on these reviews, the Agency was able to make basic health and safety determinations which show that use of tetraconazole during the period of conditional registration will not cause any unreasonable adverse effect on the environment, and that use of the pesticide is, in the public interest.

A paper copy of the fact sheet, which provides more detail on this registration, may be obtained from the National Technical Information Service (NTIS), 5285 Port Royal Rd., Springfield, VA 22161. [See EPA's April 2005 Fact Sheet - note that tetraconazole is classified as "likely to be carcinogenic to humans“ based on the occurrence of liver tumors in male and female mice.] In accordance with section 3(c)(2) of FIFRA, a copy of the approved label, the list of data references, the data and other scientific information used to support registration, except for material specifically protected by section 10 of FIFRA, are also available for public inspection. Requests for data must be made in accordance with the provisions of the Freedom of Information Act and must be addressed to the Freedom of Information Office (A-101), 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001. The request should: Identify the product name and registration number and specify the data or information desired.

•• Comments submitted to US EPA on this Notice from FAN Pesticide Project.
•• FOIA Request for documents on tetraconazole.

Pesticide Emergency Exemptions:

• New Jersey. EPA authorized the use of tetraconazole on soybeans to control soybean rust; April 25, 2005 to November 10, 2007. Contact: (Andrew Ertman)
• Tennessee. EPA authorized the use of tetraconazole on soybeans to control soybean
rust; April 25, 2005 to November 10, 2007. Contact: (Andrew Ertman).
• Vermont. EPA authorized the use of tetraconazole on soybeans to control soybean
rust; June 23, 2005 to November 10, 2007. Contact: (Andrew Ertman)

The States of Minnesota and South Dakota, as lead state agencies in what is essentially a ``national'' section 18 request for all soybean growing States... Soybean rust has been designated as a biosecurity threat and therefore, it is important that control measures be available for the disease.

For purposes of this section 18 petition, parent tetraconazole is being considered. The Agency does have concern about potential toxicity of 1,2,4-triazole and two conjugates, triazolylalanine and triazolyl acetic acid. These three compounds are metabolites to most of the triazole-containing fungicides. To support the extension of existing parent triazole-derivative fungicide tolerances, EPA conducted an interim human health assessment for aggregate exposure to 1,2,4-triazole. The exposure and risk estimates presented in this assessment are overestimates of actual likely exposures and therefore, should be considered to be highly conservative. Based on this assessment EPA concluded that for all exposure durations and population subgroups, aggregate exposures to 1,2,4-triazole are not expected to exceed its level of concern. This assessment should be considered interim due to the ongoing series of studies being conducted by the U.S. Triazole Task Force (USTTF). Those studies are designed to provide the Agency with more complete toxicological and residue information for free triazole and are expected to be submitted to the Agency in late 2004. Upon completion of the review of these data, EPA will prepare a more sophisticated assessment based on the revised toxicological and exposure databases.
The most recent estimated aggregate risks resulting from the use of tetraconazole, are discussed in the Federal Register of April 22, 2005 final rule (see below) establishing tolerances for residues of tetraconazole in/on sugarbeet and livestock commodities. In that prior action, risk was estimated assuming tolerance level residues in all commodities for established and proposed tolerances, including the tolerances for soybean and animal commodities discussed in this document.

Sipcam Agro USA. 7-year time-limited pesticide tolerance approved. Final Rule.
Objections and requests for hearings must be received on or before June 21, 2005.
Sipcam Agro USA, Inc. requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act of 1996 (FQPA). Registrations will be limited to the following States: Colorado, Minnesota, Michigan, Montana, North Dakota, Nebraska, and Wyoming where use has previously occurred under section 18 of FIFRA.

Background and Statutory Findings. In the Federal Register of October 14, 1999, EPA issued a notice announcing the filing of three pesticide petitions (9F5066, 9F6023 and 7E4830) by Sipcam Agro, USA, Inc., 300 Colonial Center Parkway, Roswell, GA 30076, formerly of 70 Mansell Court, Suite 230, Rosewell, GA 30076. The petitions requested that 40 CFR part 180 be amended by establishing tolerances for residues of the fungicide tetraconazole, in or on the following raw agricultural commodities: beets, sugar at 0.01 ppm, beets, sugar, roots at 0.1 ppm, beets, sugar, tops at 7.0 ppm, beets, sugar, pulp, dried at 0.3 ppm, and beets, sugar, molasses at 0.3 ppm, cattle, meat at 0.01 ppm, cattle meat byproducts at 2.0 ppm, cattle fat at 0.1 ppm, and milk at 0.02 ppm (9F5066); peanuts meat (hulls removed) at 0.03 ppm, peanuts meal at 0.03 ppm, and peanuts oil at 0.1 ppm (9F6023); and imported bananas at 0.2 ppm (7E4830). Petition 7E4830 was later withdrawn. Petition 9F6023 was placed in abeyance by the petitioner. There were no comments received in response to the notice of filing. The tolerances will expire on February 28, 2009.

Cancer (oral, dermal, inhalation): "Likely to be carcinogenic to humans" - Q1 * = 2.30 x 10-2, based on male mouse liver benign and/or malignant combined tumor rates

Aggregate cancer risk for U.S. population. The estimated cancer risk for the proposed use on sugarbeets and existing section 18 exemptions for soybeans is 2.5 x 10-6, a value that falls within the Agency's risk standard for cancer in the range of 1 x 10-6.

EPA concluded that the additional safety factor for the protections of infants and children could be removed:

Acute dietary, females (13- 50 years of age): Oral developmental toxicity study - rat. Developmental NOAEL = 22.5 mg/kg/day, based on increased incidence of small fetuses, and supernumerary ribs.

Chronic dietary, all populations: Chronic oral toxicity - dog. Systemic toxicity LOAEL = 2.95/3.33 (M/F) mg/ kg/day, based on absolute and relative kidney weights and histopathological changes in the male kidney

Metabolite 1,2,4-triazole: The Agency does have concern about potential toxicity to 1,2,4-triazole and two conjugates, triazolylalanine and triazolyl acetic acid, metabolites common to most of the triazole fungicides. To support the extension of existing parent triazole-derivative fungicide tolerances, EPA conducted an interim human health assessment for aggregate exposure to 1,2,4-triazole. Based on this assessment EPA concluded that for all exposure durations and population subgroups, aggregate exposures to 1,2,4-triazole are not expected to exceed its level of concern. This assessment should be considered interim due to the ongoing series of studies being conducted by the U.S. Triazole Task Force (USTTF). The toxicological database for 1,2,4-triazole is incomplete. Preliminary summary data presented by the USTTF to EPA indicate that the most conservative endpoint currently available for use in a risk assessment for 1,2,4-triazole is a LOAEL of 15 mg/kg/day, based on body weight decreases in male rats in the reproductive toxicity study (currently underway). This endpoint, with an uncertainty factor of 1,000 was used for both acute and chronic dietary risk, resulting in an RfD of 0.015 mg/kg/day. The uncertainty factor of 1,000 includes an additional 10X safety factor for the protection of infants and children. The resulting PAD is 0.015 mg/kg/day.

Drinking water.
-- EPA notes that ground water monitoring studies in New Jersey and California showed maximum residues of 16.7 and 0.46 ppb, respectively, which exceed the SCI-GROW estimates significantly.
-- With the exception of the acute DWLOCs for infants and children 1 to 6 years old, all DWLOCs are greater than the largest EEC (surface water estimate from use on turf). The EEC's for these two population groups exceed the DWLOC's by 1.1 to 3.2-fold, a result typically interpreted to mean that aggregate exposure exceeds EPA's level of concern.

The Agency is planning to conduct a more sophisticated human health assessment in 2005 following submission and review of the ongoing toxicology and residue chemistry studies for 1,2,4-triazole.

Conditions:
The following conditions will be applied to the registration of tetraconazole for use on sugarbeets:

1. Registration and tolerances will be time-limited to allow review of triazole data and completion of the triazole risk assessment.

2. Registrations will be limited to the following States: Colorado, Minnesota, Michigan, Montana, North Dakota, Nebraska, and Wyoming where use has previously occurred under section 18 of FIFRA.

3. The registrant will be required to provide one additional side-by-side sugarbeet field trial comparing two and six applications of
Eminent 125SL at 0.10 lb ai/acre/application.

4. The registrant will be required to provide a 28 day inhalation study.

5. Well documented estimates of how many pounds of tetraconazole will be placed on the market to treat sugarbeets.

6. Tetraconazole use reporting on sugarbeets. This information should be reported as how many pounds of tetraconazole will be applied per acre on sugarbeets.

Two Pesticide Emergency Exemptions.
• Michigan - EPA authorized the use of tetraconazole on sugar beets to control Cercospora leafspot; May 4, 2004 to September 30, 2004. Contact: (Stacey Groce).
• Wyoming - EPA authorized the use of tetraconazole on sugar beets to control Cercospora leafspot; May 4, 2004 to September 30, 2004. Contact: (Stacey Groce)

Application from Minnesota for Emergency Exemption. EPA has received a quarantine exemption request from the Minnesota Department of Agriculture to use the pesticide tetraconazole to treat up to 3.5 million acres of soybeans to control soybean rust. The Applicant proposes the use of a new chemical which has not been registered by EPA.
-- The Applicant proposes to make no more than two applications of
Eminent 125SL that may be made by ground or air at a rate of 1.6 ounces
active ingredient/acre (13 fluid ounces of product per acre), to 3.5 million acres of soybeans during the growing season in Minnesota and
1.4 million gallons of product may be used.
-- This notice does not constitute a decision by EPA on the application itself. The regulations governing section 18 of FIFRA require publication of a notice of receipt of an application for a specific exemption proposing use of a new chemical (i.e., an active ingredient) which has not been registered by EPA.

Emergency Exemptions for pesticide use.

• Colorado Department of Agriculture - EPA authorized the use of tetraconazole on sugarbeet to control Cercospora; May 29, 2002 to September 30, 2002.
• Michigan Department of Agriculture - EPA authorized the use of tetraconazole on sugarbeet to control Cercospora; May 29, 2002 to September 30, 2002.
• Nebraska Department of Agriculture - EPA authorized the use of tetraconazole on sugarbeet to control Cercospora; May 29, 2002 to September 30, 2002.

• Pesticide Emergency Exemptions. EPA authorized the use in:
• Colorado: on sugar beets to control cercospora leafspot (Cercospora Beticola); June 15, 2001 to September 30, 2001.
• Minnesota: on sugar beets to control cercospora leafspot; June 15, 2001 to Sept 30, 2001.
• Montana: on sugar beets to control cercospora leafspot (Cercospora Beticola); June 15, 2001 to Sept 30, 2001.
• Nebraska: on sugar beets to control cercospora leafspot (Cercospora Beticola); July 1, 2001 to Sept 30, 2001.
• North Dakota: on sugar beets to control cercospora leafspot; June 15, 2001 to Sept 30, 2001.
• Wyoming: on sugar beets to control cercospora leafspot (Cercospora Beticola); June 15, 2001 to Sept 30, 2001.

• SIPCAM AGRO - Registration Applications for TWO pesticide products.
• Tetraconazole Technical. Fungicide. Active ingredient: Tetraconazole at 97.0%. Tetraconazole Technical is intended for the formulation into end-use products for use on sugar beets, peanuts, and turf. Type registration: Conditional.
• Eminent 125SL Fungicide. Active ingredient: Tetraconazole at 11.6%. Eminent 125SL is intended for the control of Cercospora leaf spot and powdery mildew disease of sugar beets; early and late leaf spot, rust, web blotch, and southern blight of peanuts and dollar spot, copper spot, rust, Southern blight, brown patch, red thread, anthracnose, powdery mildew, etc. diseases of turf. Type registration: Conditional.

• SIPCAM AGRO - Three Petitions for Pesticide Tolerances for residues of Tetraconazole in or on the Raw Agricultural Commodities of:
• Petition 9F5066: beets, sugar at 0.01 ppm; beets, sugar, roots at 0.1 ppm; beets, sugar, tops at 7.0 ppm; beets, sugar, pulp, dried at 0.3 ppm; and beets, sugar, molasses at 0.3 ppm; and in animal commodities of milk at 0.02 ppm; cattle, meat at 0.01 ppm; cattle meat byproducts at 2.0 ppm and cattle fat at 0.1 ppm.
• Petition 9F6023: peanuts meat (hulls removed) at 0.03 ppm, peanuts meal at 0.03 ppm, and peanuts oil at 0.1 ppm.
• Petition 7E4830: imported bananas at 0.2 ppm.