United State* Office of Pesticides and Toxic Sufattaneat Environmental Protection Office of Pesticide Programs (TS-766C) Agency Washington. DC 20460 vvEPA Pesticide Fact Sheet Name of Chemical: CAPTAPOL Reason for Issuance: Date Issued: October i, 1934 Fact Sheet Number: 35 1. Description of Chemical Generic Name: cis-N-[(1,1,2,2-tetracnloroethyl) tEIo] -4-cyclohexene-l, 2-dicarboocimide Cannon Name: Captafol Trade Names: Difolatan, Polcid, Haipen, Merpafol, Ortho 5865, Sanspor and Sulfemmide EPA Shaughnessy Code: 081701 Chemical Abstract Service (CAS) Number: 2425-06-1 Year of Initial Registration: May 21, 1962 Pesticide Type: Fungicide Chemical Family: Phthalunide U.S. Producer: Chevron Chemical Ccnpany 2. Use Patterns and Formulations Application Sites: Apples (Midwestern and Eastern states only), apricots, blueberries, cherries (unspecified-use in California and Oregon only), cherries (sour), cranberries, grapefruit, lemons, limes (Florida only), macadamia nuts (Hawaii), nectarines, oranges (Florida only), peaches, pineapples, plums, prunes, tangerines, corn (sweet, Florida only), cucumbers, melons, onions, potatoes, taro (wetland) (Hawaii only), tomatoes (mechanically harvested only), watermelons, peanuts, seed treatment uses (corn (field), cotton, peanuts, rice and sorghum (grain and forage)] and wood. Types of Formulations: Dusts, emulsifiable concentrates, flowable suspensions, wettable powders, and water dispersible granules. Types and Methods of Application: Dusting, spraying, misting, and dipping under pressure for wood treatment. Application Rates: See use patterns in USDA Compilations of Registered Uses of Fungicides and Nematicides, Part I, Pages C-09-95.01 through C-09-95.11. Usual Carriers: Clay, talc, silica, water. ------- 3. Scientific Fiz ]in th nical tharacteristi : Physical State: Crystalline solid Color: ite Odor: Slight characteristic pungent odor Melting Point: Range 156—161°C (162°C, pure compound) Stability: Stable under ordinary environmental conditions. I composes slowly at melting point. Very slight hydrolytic decomposition at acid or neutral pH at ambient temperature. Strong aodium and potassiuu hydroxide solutions may cause spontaneous ignition of concentate forms. In neutral or weakly basic solution, captafol slowly decomposes at a rate depending upon pH and temperature, being very slow below 7.0 and rapid above 9.0. Toxicity Characteristics : Acute oral LD 50 — Rat — males 6780 mg/kg, Category III females 6330 mg/kg, Category III Acute inhalation LC 50 — Data gap Dermal Irritation — Rabbit — iixderate dermal irritation at 72 hours, Category III. Severe dermal sensitization. Eye Irritation — Rabbit — corneal opacity, iris and conj*mctive irritation present through day 21, Category I. Teratology — Rat — no teratogenic effects seen. Highest dose tested: 100 mg/kg/day. Rabbit — recently submitted tests currently under review. H*mater — no effect level (NOEL) for fetotoxicity and possible teratogenic effects — 300 mg/kg. New study at be submitted by the registrant. Oncogenicity —Mouse — Oncogenic lesions were observed at 1000 and - 3000 parts per million (ppm) but not at 300 ppm. Information concerning the control groups is being requested from the registrant in order for a final risk assessment to be performed. — Rat — Oncogenic lesions were seen at all dose levels. Additional histopathology examinations of liver and mammary tissues at low (56 ppm) and mid (241 ppm) dose levels have been requested from the registrant. This information is necessary f or a complete risk assessment to be performed. ------- —.‘ — Physiological and Bioth nical Bthavioral tharacteristics : Foliar Absorption: Captafol and/or its metabolites and dearadrates is (are) absorbed by roots and shoots of plants. Translocation Ca tafol and/or its metabol ites and dearadrates is (are) translocated in plant tissue. Captafol and/or its metabolites and deciradates is (are) absorbed and trarislocated within p1 ants as a result of sped treatment, soil treatn nt and foliar application. Methani n of Pest icidal Action: tfl b n Metaboli n and Persistence in Plants and Animals: The metabo1i and acc’.imilation of captafol in plants are not uri]erstocxL The metabol i n of captafol is wx3erstood for rizninants but riot for avian species. The foll ing metakolites have been identified in animal tissues: delta 4 -tetrahvdLc hthal imide r*ithal imide 4, 5-epoxyhexahvci Lcdlthal imicie 4, 5-dih drc cyhexahydL Jhthal imide 3-vdrc cy-de1 ta 4 -tetrahvdrc*ithal imide racy-de1 ta 3 —tetrah dLc*jhtha1 thiide delta 4 -tetrahy&u hthal nic acid del ta 4 - tetrahydrochtharic acid The above metabolites, with the exception of delta 4 -tetrahyck x hthalic acid, re found in milk. Pb Parent captafol per se i s detected in nm inant tissues or in milk. ------- -4- Envi Lct u. nta.l tharacteristic : Absorption and Leathing in Basic Soil Types: Captafol se does not leadi fran basic soils. The lead abi1ity and persistence of its metabolites and degr ates are not understood. Microbial Breaiuici.in: Ina)eguate data. Limited data indicate that captafol se has a half—life of <3, 5, and 8 days in nonsterile organic, sandy and clay loam soils, respectively. The soil degredates and netabolites have not been identified. Tri fran Pbotodeccuçz siticm and/or Volatilization: Inedequate data. Bioacainulation: t data. Resultant Average Persistence: In equate data on netabolites and degredates. Ecvlngical characteristics : Hazards to fish and wildlife Rainb trait: 96—hr LC j = 0.027 — 0.190 ppi Bluegill sunfish: 96—hr IC 50 0.045 — 0.230 ppe characterized as very highly t cic’ to both oold water arid warm water fish. Ina3equate data for fish acctinulation. Avian Tacicity: I D 50 = >2510 pp LCc = >5620 ppn Da mia ma a : 96-hr IC 50 = 3.34 Moderately to very highly tc cic to freshwater invertebrates. Avian Reproducticm: Strong tential for reproductive effect in birds (based on ai l entary information). Potential probl related to endangered species: Mditional data on exposure persistence, avian reproduction sti.thes, and acc .mnilation are required to c r lete the endangered species assesa nt for captafol. ------- —5— Efficacy Review Results: Captafol product registrations with EPA have been supported with efficacy data. To lerant strains of target plant patixDgens have not been reportea. Tolerance Asses nents: 1. List of Crops and Tolerances: The fo1lc ing table lists the present status for tolerances in parts per million (p n) for residues of captafol: Parts Per Million in Captaf ol Residues Raw Agricultural Caiiicdity U.S. Canada Mexico Codex Apples 0.25 0.1(N) 5.0 Apricots 30.0 0.5 15.0 Blueberries 35.0 — — Cherries, sour 50.0 10.0 10.0 Cherries, sweet 2.0 2.0 2.0 Citrus fruit 0.5 — — Corn, Fresh (sweet K+CWHR) 0.1 (N) — — Cranberries 8.0 — 8.0 Cuci.utbers 2.0 2.0 2.0 Macadamia nuts 0.1(N) — 0.1 (N) Melons 5.0 2.0 2.0 Nectarines 2.0 — — Peanuts, hulls 2.0 — —a Peanuts, meats (hulls re uved) 0.05 — 0.05 Chions 0.1(N) 0.1 (N) 0.5 Peaches 30.0 15.0 15.0 Pineapples 0.1(N) — 10.0 Plti (fresh prunes) 2.0 0.2 10.0 Potatoes 0.5 0.1(N) 0.5 Taro (corme) 0.02 — — I natoes 15.0 5.0 5.0 Carrots 0.5 ( c) MRL for whole peanuts is 0.5 ppn. 2. Seed Applications: No tolerances have been established for captafol in or on any crop for which captafol is registered solely for seed treatment or plant propagule uses, because heretofore seed treatment and plant propagule uses have been considered to be nonf cod uses. These crops include: corn (field), cotton, rice, sorgh n (grain and age, strawberries (propagating bed use), and sugarcane (seed piece use). ------- -6- Results of ‘r lerance Asses nent Sufficient data are available to determine that the currently established tolerances for residue of captafol in or on the follcMina CClmTCdities are adequate: apricots, blueberries, cranberries, macadamia nuts, nectarines, pead es, peanut hulls, and taro corms (40 CFR 180.267). However, additional data concernina residues of metabolite PI must be sutinitted for all cm dities since the residues of concern in or on plants have recently been mdjfjed to include THPI. In addition to WpI data, other residue data are required to support the tolerance for captafol in or on the following ccnin:x3ities: apples, citrus fruits, corn (sweet), cuctmbers, melons, onions, peanuts, pineapoles, plums (prunes), potatoes, arid tanatoes. I data and tolerance c’hanaes must be sutinitted for sweet and sour cherries. Residue data and tolerance proposals irust be submitted for the following cc1im ities: crops receiving only seed treabiients (cotton, field corn, rice arid sorghum), pears (state label use only), strawberries Fpropaciatina bed use: Section 24(c)l, sugarcane (seed piece use), and taro foliage. lerances for the following ccmidities are penciina: carrots, coffee beans, pecans, soybeans, and soybean forage arid hay. Plant metaboli n of captafol is not adeauatelv understood, therefore tolerance for residues other than caotafol and ‘E PI may need to be souaht if those residues are de ned to be of concern. A poultry metabolj n study will be needed. Also, feedina studies are reauired for ruminants and Doultrv. diticnal storaae stability data are necessatv to val idate the residue data. b crop aroup tolerance may be estabi ished based on the available data. The Theoretical Maximum Residue Contribution (‘1!1RC) is I .d 7Q nc/day based pn a 1.c—kq diet. The thanae in the residue definition (by including the metabolite ‘! 1PI), the reauested tolerance proposals arid the pendina tolerances noted above will affect a change in the ‘I C level. The maximum permissible intake (MPI) for a 60 kg person is 1.68 rw /day based on an acceptable daily intake (ADI) of 0.028 mg/kg. The present RC represents R6.8% of the MPI. The inclusion of the ma,or metabolite (‘t PI) in the tolerance expression may result in an increase in the RC arid a greater percentage of the MPI utilized. The DI for captafol is based on a chronic toxicity study in rats. A PEEL was established at 56 ppm for non-onooaenic effects. In that study the next hiahest dose level caused cholanaiectasis in liver, increase in hyperplasia of tubule epithelium, megalocytic cells arid transitional cell hyoerplasia in kidney, increased erosion/ulceration, hypericertosis/acanthosis, around substance in alandular mucosa, and dilated pits in stcznath. The reported dosage level was corrected fran 7 ppm to 5( ppm based on the instability of caotafol in the diet. In the rat, F pm is aporo ciinately equivalent to 2.R mq/ka. rising a safety factor o 100 and a PiZL of 2.8 mg/kg/day, the ADI uld be fl.02R ma/kg for h nans. The only reaistrant of technical captafol, theuron th nical Ozmany, has been requested to canpiete the histooatholoav examination of the low arid mid-dose liver and m inary aland tissues: therefore, the MJ L for cholanqiectasis in the liver may thanae. The CFL of 45 pan is for syst uic effects excluding ie issue of oncogenicity for which a risk asses nent will be performed. ------- Probl that are Kn n to Rave Occurred with Use of th th nical 1. Captafol is a skin sensitizer. Incidents of faam rkers being disabled fran its effect have been re rted. Restrictinq the use of captafol to nethanically harvested tanatoes, arid labeling requiri use of gl es arid protective clothing by citrus harvesters have reduced this pr.tl n. 4. &tmnary of Regulatory Positions arid Rationale Based on the cmcoaenic arid fish tc cicity potential risks of hazard, captafol is bsina placed under ecial Review by the ivirorinental Protection Agency. The pres .utptian of risk of hazards out ighirig the derived benefits n ist be rebutted by the manufacturers of pesticide pzvducts that have captafol as an active ingredient. Based on the oncogenic potential and the fish toxicity potential, captafol is classified as a “Restricted Use” pesticide. All captafol products nust be relabeled as “Restricted t e ” pesticides. The foll i labeling restrictions will be recuired for continued registration of captafol products: All tethnical orade, manufacturino-use (MtIP’s) arid end—use products ( YP’s) nust bear ppotopriate labeling as specified belc and in 4fl C ’R 1F2.lfl. 1. Precautionary statenents to be used on labeling of all end-use captafol products: a. All end-use product labels must reflect the follc* ,iriq stat nents: i rR.tCrED (BE P rIC1DE. For retail sale to, and use only by Certified applicators or persons under the direct supervision of a Certified A licator, and only for those uses co’rered by the Certified A licator’s certification. “This product is classified as a “Restricted Use Pesticide” because it contains captafol whith has been determined to cause ti.znors in laboratory animals.” cposure to captafol durina mixing, loadina, and apolication may be hazardous to your health. This product contains captafol whith has been determined to cause tuiors in laboratory animals . b. All end-use products imist have the labelina precaution under ‘Direction for t e ”: 1 ar ij pervicuS qlcwes and full body clothing during handling arid a çlication”. ------- —p — C. Al] end-use products intended for crc use, except seed, seed piece, and plant prcx aaule treatzrents must bear the foll ina use restrictions: i. i x , not rotate treated crc with cr s other than those with registered captafol uses. ii. t not al1c persons to enter treated areas within 24 hours follcNina application unless full body clothing is i rn. Ccnspicuously post reentry information at sites of app] icat ion. iii. I X , not use captafol—treated rice seed in fields subeequently to be used for agricultural crqs other than those with req istered captafol uses iiii. Water fran cranberry boqs, wetland taro fields (foliarly treated with captafol) and rice fields planted with captafol- treated rice seed must not be used for irriaation of crcos other than those with registered captafol uses. 2. For oroducts that bear label claims for use in areenhouses: a. ly the acolicator is oermitted in the areenhouse durino applicatior. of captafol to soil. ( en vents to areenhouse during apol icatior and for at least 1 hour after application. b. rkers plantina in caotafol treated soil in greenhouses must wear irpervious qlc es and full body clothing. 3. All products, manufacturina—use and end-use, must bear the labeling precautionary statanents. Causes irreversible eye d naqe. Harmful if s llcx ed or inhaled. May cause allergic skin reactions. IX, not et in eyes. Wear goqales or face shield when handling. Avoid contact with skin and clothing. R T 7e and separately launder clothing before reuse. This product contains captafol whi& has been determined to cause tumors in laboratory animals ------- —9— In a3ditión, the following specific envirorgnental hazard labeling r uir ents apply to either tedinical, manufacturing—use or end—use product as irxhcated. a. All tedinical arid IbVP’ s must bear the following precautionary state rents: This pesticide is extr nely toxic to fish. Do not disdiarge into lakes, streams, ponds, or public waters unless in accordance with an NPV permit. For guidance contact your Regional Office of the EnviroruTEntal Protection Agency. Do not disd arge effluent containing captafol into sewage syst ns without obtaining permission fran the sewage treatnent authority. b. All JP’s that allow for foliar applications except foliar application to cranberries, must bear the hazard precaution: This pesticide is extr ly toxic to fish. Do riot apply directly to water. Drift arid runoff fran treated areas may be hazardous to aguatic organi ns in neighboring areas. Do not contaminate water by cleaning of equip nt or disposal of wastes. c. All EXJP’s that allow foliar application to cranberries must bear the tol lc iing environn ntal hazard precautions: This pesticide is extr nely toxic to fish. Fish may be killed at recaiirerided application rates. Drift arid runoff fran treated areas may be hazardous to uat1c organi in neighboring areas. Do not contaminate water by cleaning of equip!ent or disposal of wastes. d. All alP’s that allow seed trea nt must bear the following enviLcAw ntal hazard precaution: This pesticide is extreit ly toxic to fish. Do not contaminate water by cleaning of equiplent or diposal of wastes. 4. Both MUP’s arid alP’s may need special labeling to protect endangered species. This will be determined after required envirorm ntal theiu.stry data are reviewed, arid in conjunction with EPA’S evaluation of the potential risk of hazards to endangered species. ------- —Jo- Rased on historical use exrierience (himian health effects reprts) and the benefits frcm the nest icide uses, the Aqencv will allc the reaistration of cantafol products to continue for existinci use—patterns until the risk of hazards is better defined tJ)r the data suh utted in resconse to the Caotafol Reaistration Standard and the caip ) etion of a Specia’ Review by the Aqencv and provided that the reauirerl labelina under the Standard is suhiiitterl within the time specified. c. &minarv of Malor Data ( acs Product thet istrv Data a Description of beainnina materials and manufacturina orocess Discussion of Formation of hypurities Preliminary Analysis o Product Samnles Density, Bulk Density, or Specific Gravity Va r Pressure Dissociation Constant Oc’tanolmater Partition Coefficient Solubility Toxicoloqv Inhalation LC 50 — Rat ( ) nfl-day feedino — dent, Non—rodent (18) fl-day Ir* al.ation — Rat (18) thronic ‘T’oxicitv - 2 snecies: xient and Non-rodent (16) C iccxjenicitv stuiy - 2 species: Rat and Mouse preferred (6) ‘Peratoqenicity 2 species - needs hamsters stix)y usina t test aroups, one dosed on day 7, and the other dose on day 8 of aestation (17) flene I&itation (17) flennal Absorption (6) Residue O, i istrv (24) Analytical Method P1 ant Metabol is Animal eta 1i (poultry) Storaae Stability Maqnitu e of Residues on all food—use crcos Envirormanta] Fate Soil Metabo1i - Aerobic soil (24) — Anaerobic aauatic (24) — Aerobic aauatic (24) Degradation — Hydrolysis (6) — Photodegrac3ation in water, soil and air (6) Dissipation — Soil (24) — Aquatic (sediment) (24) Reentry (24) a! Data to be subnitted in ntrber of months after receipt of the Oiidance for the Rereqistration of Pesticide Products Containing Captafol, EPA Case Mimber 116. ------- —) — I’ bilitv St ies ( 6 )a Lead ing and AbsorotlonA)esorpt ion Acc m ulation Sttx ies (24) J tationai Crc s Wildlife and uatic Oraani s Acute 50 Estuarine and Marine Orqani ns (6) . O ntact Person Fuqene M. Wilson Office of Pesticide Proarams Reqistraticri Division (‘PS—767C) Crystal Mall 12 1921 Jefferson Davis Hwy. Arlington, VA Telej*ione (703) 557—1900 DISaAIMER: The information in this i nical Information Fact Sheet is for informational pur ses only and may not be used to fulfill data requir nents for pesticide registration or rereqistraticn. a. Data to be sutviitted in number of months after receipt of the ( iidance for the Rereaistration of Pesticide Products Containing Captafol, EPA Case t .unber 116. ------- |