ProMctiOfi Office of Pccticid* fiegnuu (TS-7G6CJ W«hlngTbn..DC 2O460 Pesticide Fact Sheet Name of Chemical: Arsenic acid Reason for Issuance: Registration Standard Date Issued: September, 1986 Fact Sheet Number: 91 1. DESCRIPTION OF CHEMICAL Chemical Names: Arsenic acid, Orthoarsenic acid Gormen Name: Arsenic acid Trade Names: Desiccant L-1O», Hi Yield® H-10, Poly Brand Desiccant, Hi Yield* Synergized H-1O» EPA Shaughnessy Code: 006801 Chemical Abstracts Service (CAS) Number: 7778-39-4 Pesticide Types: Desiccant, Wood preservative Chemical Family: Inorganic arsenicals U. S. and Foreign Producers: Pennwalt Corporation Voluntary Purchasing Corporation 2. USE PATTERNS AND FORMULATIONS Application Sites: Terrestrial crop use on machine and stripper harvested cotton as a desiccant; Non-food use on seed crop okra (Arizona only) as a desiccant. Types of formulations: 75% soluble concentrate formulation intermediate, also used as end use product. Types and Methods of Applicationt Foliar spray (single application at least 4 and 10 days prior to harvest of cotton and okra, respect- ively.) Application Rates; Cotton — 2.94 to 4.42 pounds active .per acre Okra — 4.42 pounds active per acre (Note: 1 quart of 75% liquid = about 2.94 pounds active ingredient) Usual Carriers: Water ------- 2 3. SCI ’1CE FINDTh 3S Science stmrary : Arsenic acid is a form of inorganic arsenic. Such ccxr xxinds are acutely toxic to h*irans bj ingestion. Inorganic arsenical capc inds have been classified as Class A oncogens, den nstrating positive oncogeriic effects based on sufficient h ran epid nio1ogical evidence. The weight of evidence indicates that inorganical arsenical carixxinds are also rrutagens. M.though there is teratogenic and fetotoxic potential based on intraverictis and intraperitoneal routes of exposure, there is insufficient evidence ty the oral route to confirm arsenic acid’ s teratogenic or fetoto,dc effects. Neurotoxic effects have been den nstrat.ed after acute, subchronic and chronic exposures. The rretabolisn of arsenical cc!lpounds in h ns is well—doc nented, .it an.irral studies are not. adequate to determine no observed effect levels (t’IOELs) and acceptable daily intakes (ADIs). The envir3nnental fate of arsenic acid is not well documented. Studies to deTonstrate its fate rTust take into account the fact that inorganic arsenicals are natural constituents of the soil, and that the forrtE of inorganic arsenic rray change depending on environmental conditions. Based on very limited data, arsenic acid is not predicted to leach signi- ficantly. Although elevated levels of arsenic have been found in groun iater in Texas, the source of the arsenic cannot be determined; non—pesticide sources rray have been the cause. Arsenic acid is rtoderately toxic to birds, slightly toxic to fish and nxxierately toxic to aq iatic invertebrate species. Q nical tharacteristics : E ysical state — Pcp.ieous solution Oxidation state - pentavalent (As 5 ) Color - Pale yello ’i to pale green Odor — None Boiling point — Not available ecific gravity — 1.884 at 20°C Solubility - Readily soluble in water, forming various As salts Stability - st stable under conditions favoring oxidation and at high pH; under re&ction conditions or lo pH, pentavalent form nay convert to trivalent arsenic Unusual handling characteristics: Reacts with fabric, galvanized metals, blad iron and certain other metals resulting in deterior- ation, corrosion, or liberation of toxic gases (e.g., hydrogen, arsine). Forme of inorganic arsenic referenced in the Registration Standard Arsenic acid - H 3 AsO 4 , containing arsenic in a +5 oxidation form Sodium arsenate (Na 3 AsO 4 ) — the sodium salt of arsenic acid, also +5 Arsenic trioxide (As 2 0 3 ) - an oxide of arsenic, containing arsenic in a +3 oxidation form Sodium arsenite (NaAs0 2 ) - a sodium conpound related to arsenic trioxide, also +3 ------- 3 Ibxi 1ogica]. tharacteristics: Acute toxicity . Althcugh arsenic is kno in to be hi 1y toxic by ingestion, few animal st 1tes are available on the active ingredient, or on the fornulated products of arsenic acid. breover, the toxicity of arsenic a rrpcunds nay vary widely depending on the type of fornulation and the form of thor nic arsenic in the product. Oral (rat) - 40-100 m/kg. I ts are not a od test species, hcwever, since, alcne auong anTTal test species, they retain arsenic in their bodies withont significant excretion. Himans are knc n to be nore sensitive to acute arsenic effects than rats. I rmal — Undetermined Inhalation — Undetermined ye and cin Irritation - Undetermined Derrral Sensitization - Undetermined thronic toxicity. cogenicity : Arsenic caipc nds, including arsenic acid, have been classified as Class A onc gens. idenio1ogica1 st uies on rkers in ccpper relting and pesticide manufacturing, and on p ulations exposed to excess levels of arsenic in ll water in Taiwan are the basis for this classification. Inhalation exposure leads to lung cancers, and ingestion exposure has sho in a cxrrelation with developnent of skin cancers. The lifetii inhalation oncogenic risks to rkers frc n the cotton use have been estimated at negligible for applicators, and lO to iO for mixer/loaders. Dermal and oral oncogenic risks have not been calculated because the risk nodels are still undergoing Agency review. Conpietion of this review is expected in late 1986 or early 1987. Mutagenicity : The sodium salt of arsenic acid (sodi .nii arsenate) and the sodium salt of arsenais acid (a related form of arsenic) have been faind to be nutagenic, that is, to interact with DNA to cause heritable effects. Nun rcus assays have been conducted on cells in vitro . Other observed effects thcli 1e interference with DNA repair ir hanisn , direct toxicity to neimlian gonads, and positive effects in microbial syst . Other evidence s gests that similar effects may oc ur in vivo . Sodium arsenite is a rrore potent nutagen than sodium arsente. ------- 4 Teratogenicity/fetotoxicity : Sodium arsenate has been shc n to produce teratogenic or fetotoxic effects in haneters (15—25 nv/kg intraver xis1y); mice (40-45 mg/kg intraperitoneally); and rats (20-50 mg/kg interperit- oneally). Similar results have been obtained with sodium arsenite at 1 er dosages. These results have riot been d ti istrated using an oral route of exposure, or have been found only at dosages that also cause significant n terna1 nortality. Because the effects have been sh n only using routes of exposure that are not likely to occur with pesticide use, and because the studies were not adequate to establish no-observed effect levels (NOELs) the Agency will require an oral teratogeni city study in t species other than the rat. Reproductive effects : ! b data that neet Agency standards are available. A reproduction study on a species other than the rat will be required. Neurotoxicit ’ : Subchrcxkic and chronic exposure to arsenic xztpcunds causes peripheral and central nervous syst n neurc athy, the effects of which vary fran sli t to severe depending on the level and duration of exposure. Other subchronic and chronic effects : Inorganic arsenic ccrrpcxmds have been observed to cause cardiovascular, skin, blood, and liver arid kidney effects in huans. The sane effects have been observed in experinental anirtals. The NOEL for blood effects in dogs is 50 ppn (1.25 mg/kg). The NOEL for liver effects in rats of arsenites is 62.5 ppe and of arsenates is 125 ppn. Metabolism : The netabolism of inorganic arsenic caipounds in anui ls is well kna n. The pentavalent form, such as arsenic acid, is netabolized r reduction into the trivalent form, followed 1y transfornEtion into organic fore which are excreted within several days via the urine. All rrernnals ethibit this metabolism except rats, which retain arsenic in their bodies for up to 90 days. ysiological arid Behavioral Qiaracteristics : Mechanism of Pesticide Action - - Protein deriaturation and enzyme inactivation, resulting in desiccation of plant foliage arid stane E wironnental (Tharacteristics : Few data are available on the environmental fate of arsenic acid. Arsenic is a naturally occurring catpc*ind that is ubiquitous and exists in different fore (species) depending on environmental conditions. Arsenic acid rapidly dissolves in water. The arsenic noiety of the residue cannot be distingiished fran natural arsenic in the soil. Special environ& ental fate data are required to be su] ttitted. Studies on environmental fate of arsenic acid nust be designed to differentiate between natural and pesticide sources of arsenic. Groundwater ocncerns : Arsenic has been detected in groundwater underlying areas of arsenic acid use. Ha,iever, the source of this oontanii nation cannot be determined. Limited inforrt tion currently available s gests that arsenic acid will not leach significantly. Additional data are required to further evaluate leaching potential. ------- 5 Ecological Qiaracteristics : Avian acute toxicity: No data available Avian dietary toxicity: r 1lard duck 1606 ppm Bob. ihite quail - 168 ppn Freshwater fish toxicity: Bluegill sunfish — 66.8 ppn Rairilxw trout - 53.1 ppn quatic invertebrates: 1 phnia nagna - 6.5 ppei Based on limited data, the Agency characterizes arsenic acid as rroclerately toxic to birds l j ingestion in the diet. Arsenic acid is s1i t1y toxic to fish and riDderately toxic to aquatic invertebrates. Endangered Species : Cotton desiccant use rray pose a potential hazard to the Att iater’s Greater Prairie O icken in three Texas counties (Victoria, Refugio, and Fort Bend). The Agency has referred arsenic acid to the Office of Endangered Species, U.S. Departrent of Interior, for review as part of a group of cotton pesticides, and will require labeling to protect this endangered species. Tolerance Asses snent A tolerance of 4.0 ppn in cottonseed oil has been established for arsenic acid, expressed as arsenic trioxide (As 2 0 3 ) (40 CFR 180.180). The use on okra seed crop is a non—food use for which no tolerance is required. Because the rretabolisn and chronic effects of inorc n.ic arsenic in h ians are we1l-kna n, the Agency is riot requiring the submission of chronic feeding studies on arsenic acid Se. For regulatory purposes, and until teratogenicity and reproduction studies are submitted, the Agency has calculated a provisional acceptable daily intake (PADI) based upon studies using sodit.zn arsenate. Based upon a dog study having a NOEL of 50 ppn (1.25 mg/kg of actual arsenic) and a safety factor of 100, the PADI is 0.0165 mg/kg/day of As 2 0 3 , and the naxirrn. n permissible intake for a 60 kg person is 0.99 mg/day. Available residue data indicate that the iraxirrusn residue that will theoretically occur in cottonseed from use of arsenic acid is 0.009 mg/day. The rraxirm.mi residue therefore uses 0.009/0.99 of the maximum permissible intake, or 0.9%. R orted Pesticide Incidents In the period from 1966-1981, 8 incidents were reported to the Agency concerning arsenic acid related to its cotton use. ong these, one involved one h .man fatality and t persons hospitalized, three involved cattle, and four involved crop dar age fran spray drift of arsenic acid from nearly areas. ------- —6— 4. STJ!41A 1 OF R JIATO ’ POSITION AND RPJTIO ILE —Ar3eru.C acid is currently ungoing Agency Special. Reviedi, based upcn its oncx)genic and teratogenic effects. Products will retain registered until the conclusion of this reviej. Ne i uses, hcwever, will not be accepted. --Arsenic acid products will be restricted to use by certified appli- cators, because of its acute toxicity arid oncogenicity. —Use restrictions based upon grcund ater concerns are not warranted at the present time. —Reentry intervals are riot required because use as a desiccant does not lead to significant e osure to field orkers. —Protective clothing is specified for mixer/loaders and applicators, because of the acidic properties of arsenic acid, and its potential oncogenic risks to mixer/loaders and applicators. —E idangered species labeling stat nts are recpiired because of potential hazard to the Att ater’s Greater Prairie ChidKen in Texas. An avian residue rronitoring study is required to deterTnine actual levels of arsenic acid in avian feed itar . —Tolerances will be reassessed based upon residue and metabolism studies to be submitted. A rotational crc restriction rray be needed if follo iup crops take up arsenic acid residues fran the soil. 5. S14 A OF MMOR DATA GAPS Product d nistry data - arsenic acid Feb. 1987 Residue d enistry data — arsenic acid Feb. 1988 —Plant and ani al metaboli n —Analytical methodology for residues --Magnitude of residues in cotton ivironmental fate studies —Metaboli n in soil Dec. 1988 —Leaching Aug. 1987 —Laboratory volatility Aug. 1987 —Soil dissipation Dec. 1988 —Rotational cr studies Dec. 1989 Toxicx)logy studies —Acute toxicity Feb. 1987 —Teratology (rabbit and rrcuse or harr ter) Dec. 1987 —Reproduction (rodent other than rat) Eec. 1989 —Derrial penetration Aug. 1987 —-Glove permeability Feb. 1987 ------- —7— Eoological effects studies —Avian a ite toxicity y 1987 —Residue n nitoring study on avian food iterr Dec. 1987 — uatic invertebrate early life stage Dec. 1987 6. c0NTAC PERSON AT ERA Richard F. r untfort U.S. Enviror tenta 1 Protection Agency TS—767C 401 M St., SW Washington, D.C. 20460 703—557—1830 DISCLAIMER: The inforrration presented in this Pesticide Fact Sheet is for thfor rationa1 purposes only and nay not be used to fulfill data re uir nts for pesticide registration and reregistration. ------- |