UMH«d Swt« OH1« of ftctlcad* »nt Toxk Environmental Protoaion Office of Pwcicid* Piuy«tin (TS-7SaC) Agency Wtahlnfton. DC 20490 540/FS-88-133 &EPA Pesticide Fact Sheet Name of Chemical: Reason for Issuance: Registration Standard Date Issued: October 24, 1988 Fact Sheet Number: 48.1 1. Description of Chemical Chemical Name: 4-amino-3,5,6-trichloropicolinic acid Common Name: picioram OPP Chemical Code: 005101 Chemical Abstracts Service (CAS) Number: 1918-02-1 Year of Initial Registration: 1964 Pesticide Type: Herbicide Chemical Family: Picolinic acid U.S. Producer: Dow Chemical, U.S.A. Chemical Name: Potassium salt of 4-amino-3,5,6-trichloropicolinic acid Common Name: Picioram, Potassium (K) salt OPP Chemical Code: 005104 CAS No.: 2545-60-0 Chemical Name: Isooctyl ester of 4-amino-3,5,6-trichloropicolinic acid Common Name: Picioram, Isooctyl ester (IOE) of picioram OPP Chemical Code: 005103 Chemical Name: Triisopropanolamine salt of 4-amino-3,5,6-trichloro- picolinic acid Common Name: Picioram, TIPA salt OPP Chemical Code: 005102 Chemical Name: Triethylamine salt of 4-amino-3,5,6-trichloropicolinic acid Common Name: Picioram, TEA salt OPP Chemical Code: 005105 Chemical Name: Isopropanolamine salt of 4-amino-3,5,6-trichloropico- linic acid Common Name: Picioram, IPA salt ------- -2- 2. Use Patterns and Formulations Application Sites: Picloran, potassiun salt: Terrestrial food crop use on small grains, flax, pastures and rangeland grasses; Terrestrial noncrop use \ on noncrop agricultural areas and rights-of-way; Forestry use on forest lands site preparation. Picloram, isooctyl ester: Terrestrial noncrop use on industrial sites and rights-of-way; Forestry use on forest trees site preparation. Picloram triisopropanplamine salt: Terrestrial food crop use on small grains and pastures and rangeland; Terrestrial nonfood crop use on uncultivated agricultural areas, rights-of-way, and industrial sites; Aquatic noncrop use on drainage ditch banks; Forestry use on forest trees. Picloram, triethylamine salt: Terrestrial food crop use on pastures and rangelands. Types and Methods of Application: By ground: broadcast or spot treatment as foliar or soil spray; as a basal spot treatment, broadcast as pelletized spray; as tree injection, as frill treat- ment; as a stump treatment, as basal bark treatment, as a wick application, and as a low-volume dormant stem spray. By air: broadcast and low-volume dormant spray. Pests Controlled: Broadleaf weeds and woody plants. Application fetes: (Section 3 registrations) Picloram, TIPA salt: 0.27 to 3.00 pounds acid equivalent (Ib ae) per acre (A) Picloram, IDE: 0.5 to 3.0 Ib ae/A(mixtures or MAP) Picloram, K salt: 1.0 to 8.5 Ib ae/A Picloram, TEA salt: 0.25 to 1.0 Ib ae/A(SLNS) Types of Formulations: [represented Sec 3 registrations of the potassium salt(K)]: Formulation Intermediate: 30% ae or 34.7% acvtive ingredient (ai), Pelleted: 2% ae or 2.3 ai, 5 ae or 5.855 ai, 1Q% ae or 11.6 ai; Soluble Concentrate, Liquid: 2 Ib ae or 2^% ai, 2**.^ ai or 29.9% ai Usual Carrier: Water 3. Science Findings Summary Science Statement: Technical picloram is in Toxicity Category I with respect to acute inhalation and Categories III and ------- -3- IV with respect to other acute toxicities. Picloram has been clas- sified as Group D Oncogen (not classifiable to human carcinogenicity). Repeat oncogenicity, teratology, and reproduction studies are being required. Picloram does not appear to be mutagenic based on available data. Picloram is stable to hydrolysis, does not photodegrade under light, and is relatively stable in anaerobic loam soils and under anaerobic aquatic conditions and does not accumulate in fish. Picloram is intermediately to very mobile in soils ranging in texture from clay to loam. Picloram has been identified as a chemical with a potential to contaminate groundwater. The Agency is requiring that residue data depicting residues of HCB in plant and animal commodities be submitted. Picloram is practically nontoxic to avian species, slightly to moderately toxic to freshwater fish, and slightly toxic to freshwater invertebrates. Chemical Characteristics: Technical Picloram (Acid): Color: White Physical State: Powder Odor: Chlorine like Melting Point: 215 °C (decomposes) Bulk Density: 19.7 Ib/cu ft Solubility at 25 °C: 0.043 g/100 mL - Water 0.55 g/100 mL - Isopropanol 1.05 g/100 mL - Ethanol 1.98 g/100 mL - Acetone 0.12 g/100 mL - Diethyl ether 0.16 g/100 mL - Acetonitrile 1.85 g/100 mL - Methanol 0.06 g/100 mL - Methylene dichloride 0.02 g/100 mL - Benzene 0.001 g/100 mL - Kerosene Vapor Pressure: 6.16 x 10~? millimeters (mm) Hg at 35 °C 1.07 x ID"6 mm Hg at 45 °C Storage Stability: Stable under normal conditions. Picloram, Potassium (K) Salt (34.7% ai) Color: Dark brown Physical State: Liquid Odor: Alcoholic Bulk Density: 1.320 at 20 °C ------- -4- Toxicology Characteristics; Existing data are all based on picloram (technical) or K salt. Rirther data are requested for the IOE, TIPA salt, TEA salt, and IPA salt. Acute Toxicology - Technical (Acid); o Acute Oral Toxicity (Rats): Greater than (» 5000 ing/kg body wsight for males - Toxiclty Category IV; = 4012 mg/kg for females - Toxicity Category III o Acute Dermal Toxiclty (Rabbits): > 2000 mg/kg for males and females, Toxicity Category III o Acute Inhalation (Rat): > 0.035 mg/L for males and fanales, Toxicity Category I o Primary Eye Irritation (Rabbit): Moderate eye irritation, Toxicity Category III o Primary Dermal Irritation (Rabbit): Not an irritant, Toxicity Category IV o Dermal Sensitization (Guinea Pig): Not a skin sensitizer Acute Toxicology (K Salt); o Acute Oral Toxicity (Rat): > 5000 mg/kg for males, Toxicity Category IV; = 3536 mg/kg for females, Toxiclty Category II o Acute Dermal Toxicity (Rabbit): > 2000 mg/kg for males and females, Toxicity Category III o Acute Inhalation Toxicity (Rat): > 1.5 mg/L for males and females, Toxicity Category II o Primary Eye Irritation (Rabbit): Moderate eye irritation, Toxiclty Category III o Primary Dermal Irritation (Rabbit): Not a skin irritant, Toxicity Category IV o Dermal Sensitization (Guinea Pig): Skin Sensitizer* •Requires statement for skin Sensitization: "May Cause Allergic Skin Reaction." ------- -5- Acute Toxicology (IOE); o Acute Oral Toxlclty (Rat): > 3500 rag/kg for males and females, Tbxicity Category III o Acute Dermal Toxicity (Rabbit): > 2000 mg/kg for males and females, Tbxicity Category III o Acute Inhalation Tbxicity (Rats): > 0.35 mg/L for males and females, Tbxicity Category II o Primary Eye Irritation (Rabbits): Moderate eye irritation, Toxicity Category III o Primary Dermal Irritation (Rabbit): Mild skin irritation, Tbxicity Category III Subchronic Toxicology Studies; An acceptable 13-week subchronic feeding study in rats is available for picloram. The no-observed-effect level (NOEL) for this study was 50 mg/kg. A dose dependent increase in absolute and relative liver weights was seen at 150 mg/kg. An acceptable 6-month feeding study with dogs is available for picloram. The NOEL for this study was 7 mg/kg. A decrease in food consunption and increase in liver weights was noted at the highest dose. No subchronic feeding studies are available for the TIPA, TEA, IPA, or IOE forms of picloram. Subchronic feeding studies are required in a rodent and a nonrodent for each form of picloram. A 21-day subchronic dermal study is not available for picloram. This study is required for all forms of picloram. Chronic Feeding Studies: An acceptable 2-year chronic feeding study with rats is available for picloram. An increase in size and altered tinctorial properties of centrilobular hepatocytes occurred in males and females at the high (200 mg/kg/day) and mid (60 mg/kg/day) dose resulting in a NOEL of 20 mg/kg/day for this study. ------- -6- A chronic feeding study in nonrodents is not available for picloram and is required. Oncoqenicity Studies: The available oncogenic data for picloram include mouse and rat studies performed by the National Toxicology Program (NTP) and a rat study performed by Dow Chemical U.S.A. An oncogenic effect (neoplastic nodules) was seen in female rats at the highest dose in the NTP study. This study was unacceptable based on experimental design (too short exposure limit, insuffi- cient information to determine if a maximum tolerated dose [MTD] was attained). No oncogenic effects were noted in either the mouse study done by NTP or the rat study done by Dow. These studies were not acceptable because the available information was insufficient for determining if an MTD had been reached. The test material in all of these studies contained the contaminant hexachlorobenzene (HCB), which is classified by the Agency as a Group B2 oncogen (probable human carcinogen). Picloram was clas- sified as a Group D oncogen (not classifiable as to human carcino- genicity). The Agency is requiring that both the mouse and rat oncogenicity studies be repeated. Teratoqenicity and Reproduction: A teratogenicity study in rabbits is available for picloram. A small number of fetuses showed abnormalities such as missing ribs, omphalocele, and hypoplastic tail. Historical control data are required to evaluate the observed abnormalities. A teratology study in rats is available for picloram. No teratogenic effects were noted. Some fetotoxicity was present at the lowest dose. Because a NOEL cannot be set for the study a repeat teratology study in rats is required. A multigeneration reproduction study in rat is available for picloram. No reproductive effe:ts were observed however, too few test animals were used and no toxicity was observed at the highest dose. Therefore, a 2-generation reproduction study is required for picloram. ------- -7- No teratology or reproduction studies are available for the ester and amine forms of picloram. Teratology studies in rats and rabbits are required for all ester and amine forms of picloram. Reproduction studies are not required at this time. Mutagenicity; Picloram did not show evidence of chromosomal changes in a cytogenetlc bone marrow study exposing rats up to 2000 mg/kg of picloram. No other acceptable mutagenicity studies are available for picloram, its salt, ester, or amine forms. Additional mutagenicity data are required for picloram, its esters, and its amines. Metabolism; Available rat metabolism data are not adequate to fulfill Guideline requirements; therefore, additional studies are required. Manufacturing Contaminants; Technical picloram is contaminated with HOB, classified as a probable human carcinogen (Group B2). Dietary and nondietary risk assess- ments were performed by the Agency. Ihe Agency considered the dietary and nondietary risk from HOB to be acceptable at this time. Nitrosoamines are a potential contaminant of tertiary amines (TEA) and alkanolamines (TIPA) forms of picloram. Testing is required to show that the level of 1 ppm nitrosoamine contamination is not exceeded. Physiological and Biochemical Characteristics; Foliar Absorption and Translocation: Picloram translocates from both the roots and leaves of plants and accumulates in the new growth. Picloram is both foliar-absorbed and root-absorbed. Mechanism of Pesticldal Action: Alters nucleic acid and protein synthesis. Metabolism and Persistence in Plants: Available plant metabolism data indicate that picloram degrades to CC>2, oxalic acid, and the metabolites 4-amlno-2,3,5-trichloropyridlne and 4-amlno-3,5- dichloro-6-hydroxypicolinic acid. ------- -8- Metabolism and Persistence in Animals: Available metabolism data indicate that animals excrete 82 to 98 percent of the [14C]picloram used in dosing the animals as picloram. Environmental Characteristics; Absorption and Leaching in Basic Soil Types: Available data indicate that picloram was intermediately mobile to very mobile in soils ranging in texture from clay to loam. Adsorption of picloram pH. Addition of inorganic salts to the soil did not affect adsorption of picloram. Microbial Breakdown: Picloram degraded with half-lives of 100 to 200 days in loam soil, 200 to 300 days in silt loam soil, and greater than 300 days in loamy sand, commerce loam, clay, and sandy loam soils under aerobic conditions. Picloram was rela- tively stable in anaerobic loam soil under anaerobic aquatic soil conditions. Loss from Photodecomposition: Does not degrade. Bioaccumulation in Fish: Does not accumulate in fish. Potential to Contaminate Groundwater: Picloram has been previously identified as a pesticide with a propensity to leach into ground- water. Picloram has been reported as detected in seven States. Picloram is persistent and mobile and has a high potential to reach groundwater. Exposure to Humans: Based on available acute toxicology data the major routes of exposure appear to be through inhalation and dermal sensitization. Although technical picloram (free acid) is in Toxicity Category I based on inhalation, there is little chance of exposure to mixer/loaders or applicators because there are currently no products registered containing the free acid form of picloram. Risk to Humans: The major risk to humans appears to be from the contaminant HCB. Both dietary and nondietary risk assessments were performed. The dietary exposure to HCB occurs from the use of pesticides containing picloram on small grains and secondary residues on animal commodities. The oncogenic risk for the U.S. population based on dietary exposure was calculated to be 6. x 10-7. ------- —9— Potential nondietary exposure to HCB is to workers, mixer/loaders and applicators from use of picloram on wheat, forests, rights- of-way, and pasture/rangeland. The estimated nondietary risk to mixer/loaders and applicators ranged from 5.0 x 10-5 to 10-8. Reentry: Reentry intervals are not required because cultural practices for existing uses indicate little likelihood that field workers would be exposed to acutely toxic levels of picloram from agricultural applications. Efcoloqical Characteristics: Avian Acute Oral Toxicity (Technical): Bobwhite quail > 2250 mg/kg/day; K Salt: Bobwhite quail > 2510 mg/kg/day Avian Subacute Dietary Toxicity (Technical): Bobwhite quail > 5000 ppm, mallard duck > 5000 ppm; K Salt, bobwhite quail > 5620 ppm; IDE, bobwhite quail > 5620 ppm Acute Toxicity to Freshwater Fish (Technical): Rainbow trout = 4.3 to 19.3 ppm, bluegill sunfish = 14.5 to 23.0 ppm; K Salt, rainbow trout = 13 ppm, catfish = 14 ppm, bluegill sunfish = 24 ppm; IOE, rainbow trout =4.0 ppm, catfish =1.4 ppm, bluegill sunfish = 6.3 ppm Fish Embryolarvae Study: Rainbow trout with a maximum acceptable threshold concentration (MATC) = 0.55 < MATC < 0.88 mg/L Acute Toxicity to Freshwater Invertebrates Studies: (Daphnids, Gammarus, Pteronarcella, and Pteronarcys) = 10 to 68.3 ppm Chronic Aquatic Invertebrate Study (Daphnids): 11.8 < MATC < 18.1 "mg/L Acute Toxicity to Honey Bees (Technical): = 14.5 micrograms per bee Technical picloram appears to be moderately to slightly toxic to freshwater fish, slightly toxic to aquatic invertebrates, and practically nontoxic to birds. Chronic fish testing showed that picloram caused a reduction in rainbow trout larval survival at 2.02 mg/L and a reduction in growth at 0.88 mg/L. Picloram affected the growth and survival in cutthroat trout at 0.29 mg/L. The isooctyl ester form of picloram is moderately toxic to fish, and practically nontoxic to birds. ------- -10- The potassium salt of picloram appears to be slightly toxic to freshwater fish and practically nontoxic to birds. Phytotoxicity and Endangered Species Picloram has been shown to be a highly phyotoxic herbicide. Because of picloram1s demonstrated toxicity to nontarget plant species and its intended use pattern, picloram has been identified as being likely to jeopardize endangered plant species when used on pastures/rangeland and forests. A program is being developed by the Agency to reduce or eliminate exposure to these species to a point where use does not jeopardize these species. Tolerance Assessment: Tolerances are established under 40 CFR 180.292 for residues of the picloram. Food and Feed additive tolerance are established under 40CFR 185.4580 and 40 CFR 186.4580. These replace old Section 21 CFR 183.350 and 21 CFR 561.305. The Agency has established a R.F.D or a provisional acceptable daily intake at 0.07 mg/kg/day based on a 6-month dog feeding study (NOEL of 7.0 mg/kg/day) using a safety factor of 100. The the- oretical maximum residue contribution (TMRC) is calculated to be 0.001847 mg/kg/day, which utilizes 2.6 percent of the PADI. The tolerance assessment indicated that additional residue data are needed for wheat grain, wheat forage, wheat straw, pasture, range- land grasses, and flax. Data are required depicting residues of HCB in or on wheat grain, wheat straw, pasture and rangeland grasses, flax seed, and flax straw. Additional plant and animal metabolism data are needed. Reported Pesticide Incidents Most of the reported pesticide incidents involve crop damage and damage to other nontarget plants resulting from drift and from soil contaminated with picloram. 4. Summary of Regulatory Position and Rationale A review of available data indicates that none of the risk criteria listed in 40 CFR 154.7 have been exceeded. Therefore, no referral to Special Review is being made at this time. The Agency will continue to require that EPS containing picloram retain the "Restricted use" classification and the groundwater advisory against the use of picloram on well-drained soils. The Agency is requiring that the rat and mouse oncogenicity studies be repeated using Osborne-Mendel rats and BgC3Fi mice of both ------- -11- sexes using a commercially available technical grade plcloram uncontaminated with potentially tumorigenlc levels of HCB. The Agency has determined that basic toxicology studies are needed for the organic esters and amines of picloram in addition to the complete toxicological testing of the acid and/or K salt. The Agency will continue to require manufacturers to limit the level of HCB in the technical to a maximum of 200 ppm. The Agency is requiring nitrosamine testing for the tertiary amlne and alkanoloamlne forms of picloram. The level of nitrosoamines permitted in these forms is a maximum of 1 ppm. The Agency is requiring that a prospective groundwater monitoring study be submitted for picloram. The Agency is requiring that Tier II phytotoxicity testing be performed with the technical picloram, its salts, ester, and amine forms. The Agency is requiring that droplet size spectrum and drift field evaluation data be submitted for picloram. The Agency is requiring that additional residue data be submitted for wheat grain, wheat forage, wheat straw, pasture and rangeland grasses, and flax. The data must include residues of HCB and the results of analysis for HCB levels. The Agency is requiring that additional plant metabolism data be submitted providing complete identification and quantitation of all terminal residues. The U. S. Pish and Wildlife Service has determined that picloram is likely to jeopardize endangered plant species when used on rangeland/pastureland and forests. The Agency is developing a program to reduce or eliminate exposure of this chemical to these species. After the program is developed, notification of any additional labeling requirements will be made. The Agency is requiring that the labels of products containing picloram determined to be skin sensltlzers include the state- ment "May cause allergic skin reaction after multiple exposure" on the labels The Agency will not approve any significant new food uses for picloram while major data gaps exist. When additional data are evaluated the Agency will determine whether significant new uses may he- established. ------- -12- 5. Summary of Data Gaps Requirements Due Dates Product Chartistry 6 to 15 months Residue Data 6 to 24 months Toxicology Data 9 to 40 months Environmental Fate 9 to 39 months Groundwater Monitoring 9 months Plant Protection 9 months 6. Contact Person at EPA Robert J. Taylor Product Manager 25 Fungicide-Herbicide Branch Registration Division (TS-767C) Office of Pesticide Programs Environmental Protection Agency 401 M Street SW. Washington, DC 20460 Phone: (703) 557-1800 DISCLAIMER: The information presented in this Pesticide Fact Sheet is for informational purposes only and may not be used to fulfill data requirements for pesticide registration and reregistration. ------- &EPA U.S. Environrnental Protection Agency Office of Pesticide Program (TS-757C) PMSD, Information Services Branch 401 M Street, S.W. Washington, D.C. 20460 Official Business Penalty for Private Use $300 First Class Mail Postage and Fees Paid EPA Permit No. G-35 ------- |