kt1tnd S t Offi of P tIcid end Toxic S ancus Envlronmsnt.I P,ot .on off.c of P idd. Pvoqrsms ITS-766C) Aguncy W iInq n. DC 20460 &EPA Pesticide Fact Sht. Name of Chemical: i EIC HYDRAZIDE Reason for Issuance: REGISTRATION STANDARD Date Issued: JUNE 30, 1988 Fact Sheet Number: 170 1. Description of th nical Generic Name: 1 , 2-dihydro-3 ,6-pyridazinedione Cc imon Name: Maleic Nydrazide Trade Names: Drexel Sucker-Stuff, Super Sucker tuf, Retard, &irtolin, Deo.it, Drexel Sprout Stop, Fair 2, Fair Plus, RMH, Maintain 3, Malazide, Mazide, Regulox W, Regulox SCM, Stuntman, Super-De-Sprcxit, VendaJhyde, Vondrax, Royal MH-30, Royal MH-30 SG, Royal Slo-Gro, Malazide Sb Gro. EPA Shaughnessy Codes: Maleic Hydrazide: 051501 Potassi xn Salt of Maleic Hydrazide: 051503 Diethanolarnine Salt of Maleic Hydrazide: 051502 Chenical Abstracts Service (CAS) Nuther: 123-33-1 Year of Initial Registration: 1952 Pesticide 1 pe: Herbicide, Plant GrcMth Regulator U. S • and Fore ig i Producers: Drexel thanical Trans Chanical Industries .1 2. Use Patterns and Formulations : Application Sites: Terrestr al food (potatoes, onions, cranberries), terrestrial nonfood (nonbearing citrus and nonbearing apples, tobacco), terrestrial none rop. rpes and Methods of Application: Primarily as a foliar spray with sane use by tree injection. ------- Pests Controlled: Sucker control for tobacco, sprout infiltration in onions and potatoes, growth retardant of quackgrass, wild onions, and rlic. Application Rates: Terrestrial Food Crops: 0.7 lb acid eauivalent (ae)/A to 15 lb ae/A Terrestrial Nonfood Crops: 1.5 to 4.5 lb ae/A Ornamental Plants and Forest Trees: 0.06 to 6 lb ae/A Turf: 0.75 to 6.6 lb ae/A Rights—of—way: 0.66 to 6.6 lb ae/A Types of Formulation: 90%, 95%, 97%, and 99% technical grade of the active ingredient ( TcAI) 0.66 to 2.25 lb ae/gal uulsifiable concentrate (EC) 0.6, 1.5, 2.0, 2.25, and 2.5 ae/gal soluble concentrate/liquid (SC/r.J Usual Carrier: Water 3. Science Findinqs Suirmary Science Statement : Maleic hydrazide (MH) has 1cM acute toxicity (Category III) for primary eye irritation and is in Category IV for acute oral toxicity, acute dermal toxicity, and primary dermal irri- tation. MH caused no adverse reproductive effects and was not oncogenic in mice. The teratology study in rabbits had a teratogenic NOEL of 100 mg/kg with malformed scapulae occurring in the mid and high d e. Additional information has been r uested to clarify this effect. MR was stable to hydrolysis and photodegradation in soil. It photodegraded in buffered aueous solutions at pH 5, 7, and 9. MR was very irobile in five soils and has a l potential to bicaccuiru— 1. te in ftsh. Addit cnai r r 1s ence - d 1e ±inrj d t arc r ded o evaLiate M i potential co contaminate grc ind wacer. NH is cori idered pr ctical1y nontox c to bir3s, uatic inver ebrates. fresh’ ater fisti, or boney bees. nd ngered nirrai species a .e not expected to be adversely affected by the use of MR. Since no endan- gered plant species are listed for tobacco cropland, citrus, apples, or cropland with onions, potatoes, or cranberries, little risk to endangered plants is expected fran these uses. The hazard evaluation for listed plants and the right—of—way uses is being deferred until caripletion of the noncrops cluster. Chemical Characteristics: Color: White Physical state: Crystalline solid —2— ------- Odor: Faint Melt!ng point: 292 °C wini r3Iri Bulk density: 30 to 36 1b cubic feet (cu/f t) (0.049 grams/milliliter g/ml) Specific gravity: 1.6 at 20 °C Solubi]ity: 90% a.e.— 60 parts per million ( in) water 10 m isopro ’l alcohol < 10 p n xylene 240 ppn dimethyl formamide Vapor pressure: < 1 m Hg at 20 °C Stability: Stable at 45 °C up to 61 days Stable at 80 °C up to 30 days Toxicology Characteristics: Existing data are all based on NH (technical) or the potassium salt (K salt), further data are requested on the diethano]amine (DEA) salt. Acute Toxicology: Acute Oral Toxicity (Rat): Greater than C>) 5 grams/kilogram (g/kg) Toxicity Category IV Acute Dermal Toxicity (Rabbit): > 20 g/kg Toxicity Category IV Primary Eye Irritation: Primary Irritation Score (P 15) 0.4 Toxicity Category III Primary Dermal Irritation: slight Irritant Toxicity Category IV Acute Inhalation and dermal sensitization studies are not available rd are beinq r 1u re f’v “H nd the DF .c lt. Subthronic Toxicology Studies: There are no data available for subchronic oral, dermal, or inhalation toxicity. A 21—day dermal toxicity study is required for both NH (technical NH or potassium (K) salt are considered equivalent) and the diethanolamine (DEA) salt. Subchronic feeding studies for a rodent and nonrodent are not required because chronic feeding studies are required. Chronic Feeding/Onco nicity Studies: Available chronic feeding studies are inadequate to fulfill guideline requir nents but are useful to calculate provisional allowable daily intake (PADI). The chronic feeding study in rats indicates that the no-observable—effect level (M)EL) is less than Co 500 milligrams/kilogram (rn/kg). Chronic feeding studies on rodents and nonrodents are required for both NH and its DEA salt. —3— ------- Available oncogenic studies in rats are inadequate for maleic hydrazide technical and K salt, no data are available for the DEA salt, therefore data are required for both technical and DEA salt. Two oncogenicity studies are available for mice. Together they indicate that MM is not oncogenic in mice up to 1800 mg/kg. An oncogenic study in mice is required for the IDEA sa.lt. Teratology and Reproduction Studies: A teratogenicity study in rabbits sh ed that exposure to 300 or 1000 mg/kg resulted in n lformed scapulae in offspring, while 100 mg/kg had no effects. Additional information is required on parentage of affected off- spring to fully evaluate this effect. No teratology data are available for rats. Therefore, teratology studies are required for both MM and its DEA salt. A teratology study in rabbits is required for the DEA salt. A 2—generation rat reproduction study indicated no incidence of adverse reproductive effects up to 2250 mg/kg (highest dose tested [ HDT)) with feLal toxic and maternal toxic NOEL of 750 mg/kg based on decreased body weights at the HDr. This study satisfies the requirement for the MM technical. A 2—generation reproduction study in rats is required for the DEA salt. Mutagenicity Studies: A nutagenicity study of sex—linked recessive lethal gene imitations in Drosophila revealed no sex—linked reces- sive lethal imitations at cytotoxic doses of 0.4 to 1.0% K salt of MM. All other mutagenicity data are required for MM. A full set of mutagenicity studies for the DEA salt are required. Met’ iis udj : ihere . re o m t oiiSi t uth z av ia l fo MM technical or the DEA salt: therefore, these studies are required. Physiolcsical and Behavioral Characteristics: Foliar Absorption - Absorbed by roots and leaves. Translocation — Rapidly translocated to leaves and grc ving shoots. —4— ------- Me thanism of Pesticidal Action — A uracil antj.rnetabolite whidi interferes with cell division, plant growth, and maturation. Metabolism in Plants — Limited available data indicate that the major residues in tobacco are maleic hydrazide and its beta—D--glucoside conjugate. Additional plant metabolism data are r uired for potatoes, onions and cranberries. Metabolism in Animals — No data are available for metabolism in animals; therefore, livestock metaboli data is r uired. —5— ------- Environmental Characteristics: Adsorption and Leaching in Basic Soil Types: was very mobile in a silt loam, a sandy clay loam, a sandy loam, and two sandy soils. Additional leaching and adsorption data are re ui red. Microbial Breakd m: Available aerobic/anaerobic soil metabolism data are insufficient. Therefore, aerobic and anaerobic soil metabolism studies are ra uired. Loss fran Photodecanposition: Stable to photodegradation in soil. Photodegraded in buffered ueous solutions at pH 5,and 7,and 9 with half—lives of 58 days, at ph 5 and 7 and 34 days at pH 9. Bioaccuzrulation: L potential to bioacculTulate in fish. Potential to Contaminate Ground Water: The available data are inconclusive for defining potential of MH to leach into ground water. ?U1 is persistent in water. Once persistence data fran aerobic/anaerobic soil metabolism data and additional leaching data are subnitted, the potential to contaminate ground water will be evaluated. Exposure to Humans: Humans may be exposed to maleic Hydrazide by ingestion of residues on treated crops, and fran use of treated tobacco. The major route of exposure for applicators is expected to be dermal contact • An exposure assessment was performed for application on tobacco, potatoes, onions, and rights—of-way. Exposure ranged fran less than 0.5 lTg/kg/day to 16 mg/kg/day. The greatest exposure occurred for the open—pour mixer loader. Risk to Humans: The major routes of exposures are expected to be dermal and eye contact. A risk assessment was performed fcr d rr:3 p’xuc t applicators tias 2 cn i teratogenic effect (malformed scapulae in offspring) seen in rabbits. The risk assessment indicated that the margin of F I-y (r’ O5) for mixer—lnad rs ia l cs Lh )OO and th reEore of concern. Labels for end—use products (CPs) are being amended to r uire long sleeve shirts, long pants, ch nical resistant gloves at all times while handling, applying, mixing, or loading the product. Reentry: Reentry data are not r uired at this time because cultural practices for existing uses indicate little likelihood of expo- sure or lc exposure fran these uses. Because MH is placed in Toxicity category iv for acute oral and derinal toxicity, minimal risk to humans is expected. -6- ------- Ecological Characteristics: Avian Acute Adult Toxicity: Technical: Mallard Duck > 4640 mg/kg K salt: Mallard Duck > 2250 mg/kg Avian Dietary Toxicity: Technical: Mallard Duck > 10,000 n Bobwhite Quail > 10,000 ppm K salt: Mallard Duck > 5620 pn Acute Toxicity to Freshwater Fish: Technical: Rainbow Trout = 1435 n Bluegill 1608 ppm K salt: Rainbow Trout > 1000 n Acute Toxicity to Freshwater Invertebrates: Technical: 107.5 ppm K salt: 1000 ppm Acute Toxicity to Honey Bee: > 36.26 uqJbee These data indicate that MH is considered “very low toxicity” to avian species, both warmwater and col ater fish, freshwater invertebrates, and honey bees. Hazard to Endangered Species: Endangered animal species are not expected to be adversely affected by the use of MH because of its low toxicity to maiTunals, avian species, and uatic species. Since MH Is a plant ar th tet rdant danc ered plant s ecIes #ccurriIig I areas wh ce t H is used cc uId t. risk. Kci ’JE ver, there are no endangered plant species listed for tobacco crcp- land, citrus, apples, or cropl. nd planted with potatoes, onions, Cr th ’ceforz n..., risk ( .0 er gercd p1. it p c iv s. Evaluation of hazard to indangered plants fran use of MH on right-of-way will await canpietion of noncrop cluster. Tolerance Assessment: Tolerances are established in 40 CFR 180.175 for residues of the herbicide and plant growth regulator MH (1,2—dihydro—3,6—pyridazinedione) in or on the following raw agricultural cc*rinodities: —7— ------- CaTunodity Parts per million Cranberries 15.0 Onions, dry bulb 15.0 Potatoes 50.0 A tolerance is established in 21 CFR 193.270 for residues of the herbicide and plant gr ith regulator (1,2—dihydro—3,6—pyrjdazine dione) on potato chips at 160 ppm as a result of application of the pesticide to the growing potato plant. A Provisional Acceptable Daily Intake (PADI) for MR is currently based on the finding of renal dysfunction in the rat chronic study. The LOEL for this effect was 500 ng/kg/ day. Using a thousandfold safety factor, the PADI for MR is 0.5 mg/kg/day. Existing tolerances produce a theoretical maximum residue contribution ( MRC) of 0.085 mg/kqjday which occupies 17 percent of the PADI. The tolerance assessment indicated that additional residue data are needed for onions, potatoes, nonbea ring apples, and nonbearing citrus. Additional plant metabolism data are required for MN. No storage stability or animal metabolism data are available; therefore, these data are required. Available toxicology data that was used to calculate the PADI on technical or K salt include oncogenicity studies in mice, a teratology study in rabbits, and a 2—generation rat reproduction study. Additional data required include chronic feeding studies with a rodent (although the PADI was established based on a supplementary feeding study in rats) and nonrodent oncogenenicity and teratology studies in rats, lnutaqer.icity testin9, and rat metabolis n data for the techn±cdl or K salt. Data zequired to sup or tolerances for the DEA salt include acute data, chronic feeding studies with a rodent, non—rodent, oncongenicity studies in rats €irc inic ter3tolcqy studies w:L raL u rabbits 2—ge c t1cn rat reproduction study, mutagenicity testing and metabolism data. Reported Pesticide Incidents Data fran the Pesticide Incident Monitoring System (PIMS) reports and the national study of hospitalized pesticide poisonings (1971—76) show some cases of MN poisonings, mostly occupational. There were an estimated eight persons hospitalized in the United States each year fran 1974 to 1976. The circun tances that led to these poisonings are not known. —8— ------- 4. Suirrnary of Requlatory Position and Rationale A review of the available data indicate that no risk critera listed in 40 CFR 154.7 have been met or exceeded for Ma. The Agency will not approve any significant new uses of MH until additional residue chemistry data are available to assess existing uses. The Agency is requiring that labeling on all EP5 include a requirexrent for protective clothing long—sleeve shirt, long pants and chemical resistant gloves at all times when handing, applying, mixing, or loading pesticide. Products bearing labelling not in caipliance with the registration Standard may be released for shipment by the registrant only until July 30, 1989. Such products may be distributed and sold by other persons only until July 30 1990. The Agency is requiring that additional leaching, aerobic! anaerobic soil metabolism and dissipation data be sulinitted to fully define the P I potential to leach and contaminate groundwater. The Agency is requiring that additional information be subnitted on the rabbit teratology study and that a rat teratology be canpieted within twelve (12) months. The Agency will continue to require that the acceptable limit of hydrazine occurring in technical products be l5ppai as required by the PD—4 The Agency has determined that all toxicology studies will be necessary for the diethanolamine salt of maleic hydrazide if n nufacturers cir . 1 . Ych f-hr ria,a qi i.’iei. ich res’1 ed n the suspensiofl of all DEA—NH products in November 1981. The Agency has determined that all end use product chemistry data for technical. Ma must be resubnitted and updated. The Agency has determined that all products containing the DEA salt must be tested for nitrosamines. The Agency has determined that reentry data or restrictions are not required at this time. —9— ------- The Agency will not require labeling to protect endangered species at this time for products containing maleic hydrazide. The Agency has determined that Tier I nontarget area phytotoxicity testing will be required for MH. The Agency will not require additional residue data on cranberries. The Agency will require additional residue data on potatoes, onions, tobacco, nonbearing citrus, and nonbearing apples. The Agency is requiring additional animal and plant metabolism data and storage stability data on all residue data previously submitted and any new residue data requested. The Agency has determined that certain data essential to the Agency’s assessment of this pesticide and its uses and/or that may trigger the need for further data will receive iirmediate review when submitted. These data include animal and plant metabolism data, data necessary to determine the MN potential to contaminate ground water, and all requested toxicology data. 5. Surrirbar.j of Major Data Gaps R uir e ments Due Dates Product Chemistry 6 to 15 months Residue Data 6 to 24 months Toxicology Data 9 to 50 months Environmental Fate 9 to 39 months Plant Protection 9 months 6. Contact Person at EPA : Robert 7. Taylor (PM 25) Fungicid6—} erbi iUe 3rat cL Registration Division (TS—767C) Environmental Protection Agency 401 M Street SW. Washington, D.C. 20460 (703) 557—1800 DISCt IMER: 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. —10— ------- |