FINAL DRAFT United States Environmental Protection Agency 4>EPA Research and Development HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT FOR ENDOTHALL Prepared for OFFICE OF SOLID WASTE AND EMERGENCY RESPONSE Prepared by Environmental Criteria and Assessment Office Office of Health and Environmental Assessment U.S. Environmental Protection Agency Cincinnati, OH 45268 DRAFT: DO NOT CITE OR QUOTE NOTICE cument 1s a preliminary draft. It has not been formally released Environmental Protection Agency and should not at this stage be o represent Agency policy. It 1s being circulated for comments ilcal accuracy and policy Implications. ------- DISCLAIMER This report 1s an external draft for review purposes only and does not constitute Agency policy. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. 11 ------- PREFACE Health and Environmental Effects Documents (HEEOs) are prepared for the Office of Solid Waste and Emergency Response (OSWER). This document series Is Intended to support listings under the Resource Conservation and Recovery Act (RCRA) as well as to provide health-related limits and goals for emer- gency and remedial actions under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and Information obtained for Agency Program Office files are evaluated as they pertain to potential human health, aquatic life and environmental effects of hazardous waste constituents. The literature searched for In this document and the dates searched are Included In "Appendix: Literature Searched." Literature search material Is current up to 8 months previous to the final draft date listed on the front cover. Final draft document dates (front cover) reflect the date the document Is sent to the Program Officer (OSWER). Several quantitative estimates are presented provided sufficient data are available. For systemic toxicants, these Include Reference doses (RfDs) for chronic and subchronlc exposures for both the Inhalation and oral exposures. The subchronlc or partial lifetime RfD 1s an estimate of an exposure level that would not be expected to cause adverse effects when exposure occurs during a limited time Interval I.e., for an Interval that does not constitute a significant portion of the Hfespan. This type of exposure estimate has not been extensively used, or rigorously defined as previous risk assessment efforts have focused primarily on lifetime exposure scenarios. Animal data used for subchronlc estimates generally reflect exposure durations of 30-90 days. The general methodology for estimating subchronlc RfDs 1s the same as traditionally employed for chronic estimates, except that subchronlc data are utilized when available. In the case of suspected carcinogens, RfDs are not estimated. Instead, a carcinogenic potency factor, or q-j* (U.S. EPA, 1980), Is provided. These potency estimates are derived for both oral and Inhalation exposures where possible. In addition, unit risk estimates for air and drinking water are presented based on Inhalation and oral data, respectively. Reportable quantities (RQs) based on both chronic toxlclty and carclno- genldty are derived. The RQ Is used to determine the quantity of a hazard- ous substance for which notification Is required In the event of a release as specified under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). These two RQs (chronic toxlclty and carclno- genldty) represent two of six scores developed (the remaining four reflect 1gn1tab1l1ty, reactivity, aquatic toxlclty, and acute mammalian toxlclty). Chemical-specific RQs reflect the lowest of these six primary criteria. The methodology for chronic toxlclty and cancer based RQs are defined In U.S. EPA, 1984 and 1986a, respectively. 111 ------- EXECUTIVE SUMMARY Endothall (145-73-3) 1s a colorless or white solid at room temperature (Martin and Worthing, 1979; Worthing and Walker, 1983). It Is soluble In common organic solvents and soluble 1n water (Worthing and Walker, 1983; Hartley and K1dd, 1983). Pennwalt Corp. 1n Wyandotte, MI, 1s the only current domestic manufacturer of this compound (SRI, 1987; USITC, 1987). Its current U.S. production volume 1s not available. Various formulations of endothall are used as preemergence and postemergence herbicides, turf herbicides, aquatic herbicides and alglddes, deslccants for alfalfa and clover, and cotton harvest aids (Worthing and Walker, 1983; WSSA, 1983; Melster, 1988). Tradenames Include Accelerate, Aquathol K, Des-1-cate, Herbicide 273 and Hydrothol 191 {Melster, 1988). If released to the atmosphere, endothall Is expected to exist predomi- nantly In aerosol form and may be removed by either wet or dry deposition. Photolysis Is not expected to be an environmentally relevant fate process (Relnert and Rodgers, 1984). If released to soil or water, endothall would be subject to rapid blodegradatlon under appropriate conditions. Field and laboratory studies Indicate that endothall generally has a half-life of <1 week 1n surface waters under aerobic conditions (S1ms1man et al., 1976; Relnert et al., 1985, 1986, 1988; S1kka and R1ce, 1973; Relnert and Rodgers, 1987; Holmberg and Lee, 1976; Langeland and Warner, 1986). This compound blodegrades more slowly In water under anaerobic conditions and has a half-life of ~2 months (Slmslman et al., 1976). Arthrobacter sj>., Isolated from sediment, metabolized 14C-endothall under aerobic conditions and Incorporated the 14C Into glutamlc, aspartlc and citric adds, and to a lesser extent alanlne, phosphate esters (not positively Identified) and 1v ------- other unidentified compounds (S1kka and Saxena, 1973). Endothall 1s not expected to degrade chemically, volatilize or adsorb significantly In water or soil (Relnert and Rodgers, 1984; Relnert et al., 1988; S1ms1man and Chesters, 1975; Swann et al., 1983). The blodegradatlon half-life of this chemical In soil Is <7 days and 1t Is expected to persist more 1n soils with high adsorption capability. Rapid blodegradatlon 1s expected to limit the extent of leaching through soil. The most common route of human exposure to endothall Is probably dermal contact by workers Involved In the manufacture, handling or application of the herbicide (HSDB, 1988). The general public could potentially be exposed by Ingestlon of contaminated crops. Monitoring data for endothall In environmental media (air, water, soil and food) were not located 1n the available literature dted In Appendix A. The potassium and sodium salts of endothall are the forms least toxic to both aquatic vertebrates and Invertebrates, with 96-hour LC s Of >IQQ mg/l. In contrast, 96-hour LC5Qs for the amlne and copper salts are <1 mg/i for a variety of aquatic organisms. Water hardness did not Influence the toxlclty of dlsodlum or dlamlne salts to bluegllls (Inglls and Davis, 1973) and pH did not affect the toxlclty of Aquathol K to bluegllls (Mayer and Ellersleck, 1986). The toxlclty of Aquathol K to blueglll sunflsh Increased 5-fold when the test temperature Increased from 7 to 24°C (Mayer and Ellersleck, 1986). The 14-day LC5Q of endothall to juvenile Chinook salmon, Onchorynchus tshawytscha. was 62.5 ppm (Llgourl et al., 1983). Surviving fish demon- strated poor survival when transferred to seawater but good survival when transferred to freshwater. The 10-day growth EC5Qs for various species of marine algae exposed to the amlne and dlpotassium salts ranged from 225-3000 ------- ppm (Walsh, 1972). No short- or long-term effects were observed among natural populations of organisms 1n ponds or reservoirs treated with <5 mg/i endothall. Experimental evidence suggests that endothall 1s not likely to bloaccu- mulate 1n aquatic organisms. S1kka et al. (1975) reported that bluegllls took up <1% of the available herbicide from water over a 96-hour period. Isensee (1976) reported bloaccumulatlon ratios of 63, 36, 150 and 10 for algae, snails, daphnlds and fish. Serns (1977) was unable to detect endothall residues 1n tissues of bluegllls from a pond that had been treated 3 days earlier with endothall to give a concentration of 5 mg/i. Relnert and Rodgers (1986) were unable to detect endothall residues In tissues of bluegllls from a reservoir that had been treated 7 days earlier with 2 mg/l endothall. Relnert et al. (1988) reported BCFs of 3.9, 12.1 and 768.9 for the dlpotasslum salt of endothall In watermllfoll, but discounted the highest value because of experimental errors. Data obtained from rats of both sexes treated with a single oral dose of 14C-endothall suggest that gastrointestinal absortlon 1s poor (Soo et al., 1967). Peak tissue concentrations occurred within 1 hour In all tissues sampled except the Intestine. The absorbed radioactivity occurred predomi- nately 1n the stomach and Intestine (-99% of the administered radioactiv- ity). About 1% of the administered radioactivity occurred 1n the liver and kidneys. Radioactivity was not found In fat or milk, and was essentially eliminated from all tissues within 72 hours. At least 85% of the adminis- tered dose was excreted 1n the feces, but ~20% of this was unchanged com- pound and 80% was bound In some form. It seems more likely that the bound form 1s endothall that Is adsorbed onto gastrointestinal contents rather than an endothall conjugate. Small quantities were excreted In the urine (~6%), apparently as unchanged compound, and In the breath as CO- (~3%). v1 ------- Minimal data were located In the available literature regarding the health effects of endothall. Acute toxlclty appears to be substantially greater for the add form than for the dlsodlum salt. Oral LD5Q values for rats of 38-57 mg/kg have been reported for the add form (Worthing and Walker, 1983; Galnes and Under, 1986) and 182-197 mg/kg have been reported for the dlsodlum salt. Acute exposure to large doses Is extremely Irritating and causes erosion and hemorrhage of the stomach (Allender, 1983; Brleger, 1953b). Subchronlc data suggest that dogs may be more sensitive than rats to oral exposure to endothall. In a dietary study, rats succumbed to dosages of the Ion of 400 mg/kg/day and exhibited liver and kidney lesions at 40 mg/kg/day (Brleger, 1953a). Dogs treated by capsule, however, died at 20 mg/kg/day dlsodlum endothall (16 mg/kg/day endothall 1on) and had congestion and edema of the stomach at 0.8 mg/kg/day of endothall Ion (Brleger, 1953b). The Investigators suggested that the lesions In the stomach resulted from the administration of the undiluted test substance without food. There are notable discrepancies between the subchronlc and chronic data. For example, no toxic effects were reported In a 2-year dietary study where rats were exposed to 2500 ppm dlsodlum endothall (100 mg/kg bw/day of endo- thall 1on) (Brleger, 1953b). In a 2-year dietary study using dogs (4/dose), elevated relative and absolute stomach and small Intestine weights were Increased with dlsodlum endothall at 300 and 800 ppm (6 and 16 mg/kg/day of endothall 1on), but no effects were observed at 100 ppm (2 mg/kg/day of the Ion) (Keller, 1965; Penwalt Agchem, n.d.). Developmental toxldty studies using rats suggest that the dams are more susceptible than the fetuses to oral administration of endothall (Science vll ------- Applications, Inc., 1982). In a dietary study pregnant rats were given 0, 8, 16 or 24 mg endothall 1 on/kg/day on gestation days 6-19. Maternal deaths occurred at the two higher doses but the fetuses of the surviving dams exhibited no signs of teratogenldty or fetotoxldty. A NOAEL of 8 mg/kg/day was Identified from this study for teratogenldty based on maternal effects. In a 3-generat1on reproductive study, no effects were observed when rats were exposed to dlsodlum endothall 1n the diet that provided a dosage of endothall Ion at 4 mg/kg/day (Scientific Associates, 1965). In the same 3-generat1on study, however, pups 1n the 12 mg/kg/day group had reduced body weights and pups 1n the 100 mg/kg/day group died within a week of birth. Endothall has not been adequately tested for carclnogenldty. There was no evidence of carclnogenldty 1n rats fed diets containing dlsodlum endothall at <2500 ppm {100 mg/kg/day of the 1on) for 2 years 1n an early study (Brleger, 1953b). Endothall Induced transformation of BALB/c 3T3 cells (LUton B1onet1cs, Inc., 1981). Endothall was not mutagenlc In microorganisms (Andersen et al., 1972; Remondelll et al., 1986; Microbiological Associates, 1980a; Sandier and Ham1lton-Byrd, 1981) and 1n human lymphocytes (Vlgfusson, 1981). Mixed results were obtained In Drosophla (Wilson et al., 1956; Sandier and Hamllton-Byrd, 1981). The NOEL for gastrointestinal effects 1n dogs from the chronic oral dog study (Keller, 1965; Pennwalt Agchem, n.d.) was used as the basis for a verified RfD of 0.02 mg/kg/day for endothal. This RfD 1s adopted as the RfD for chronic oral exposure as well as subchronlc oral exposure to endothall for the purposes of this document. An RQ of 1000 was calculated from the effect level for gastrointestinal effects In the same study. Endothall 1s assigned to EPA Group D because of Insufficient animal carclnogenldty data; therefore, no q,* or cancer-based RQ can be derived for endothall. ------- TABLE OF CONTENTS Page 1. INTRODUCTION 1 1.1. STRUCTURE AND CAS NUMBER . . 1 1.2. PHYSICAL AND CHEMICAL PROPERTIES 1 1.3. PRODUCTION DATA 2 1.4. USE DATA 2 1.5. SUMMARY 2 2. ENVIRONMENTAL FATE AND TRANSPORT 4 2.1. AIR 4 2.1.1. Chemical Degradation 4 2.1.2. Physical Removal Processes 4 2.2. WATER 4 2.2.1. Chemical Degradation 4 2.2.2. Volatilization 4 2.2.3. Adsorption 4 2.2.4. Persistence 5 2.3. SOIL ' • . . 9 2.3.1. Chemical Degradation 9 2.3.2. Volatilization 9 2.3.3. Persistence 9 2.3.4. Adsorption 10 2.4. SUMMARY 10 3. EXPOSURE 12 4. ENVIRONMENTAL TOXICOLOGY 13 4.1. AQUATIC TOXICOLOGY 13 4.1.1. Acute Toxic Effects on Fauna 13 4.1.2. Chronic Effects on Fauna 24 4.1.3. Effects on Flora 26 4.1.4. Effects on Bacteria 28 4.2. TERRESTRIAL TOXICOLOGY 28 4.2.1. Effects on Fauna 28 4.2.2. Effects on Flora 28 4.3. FIELD STUDIES 28 4.4. AQUATIC RISK ASSESSMENT . 30 4.5. SUMMARY 31 1x ------- TABLE OF CONTENTS (cont.) Page 5. PHARMACOKINETCS 33 5.1. ABSORPTION 33 5.2. DISTRIBUTION 34 5.3. METABOLISM 35 5.4. EXCRETION 35 5.5. SUMMARY 36 6. EFFECTS 37 6.1. SYSTEMIC TOXICITY 37 6.1.1. Inhalation Exposure 37 6.1.2. Oral Exposure 37 6.1.3. Other Relevant Information 38 6.2. CARCINOGENICITY 39 6.2.1. Inhalation 39 6.2.2. Oral 39 6.2.3. Other Relevant Information 39 6.3. MUTAGENICITY 39 6.4. TERATOGENICITY 39 6.5. OTHER REPRODUCTIVE EFFECTS 41 6.6. SUMMARY 41 7. EXISTING GUIDELINES AND STANDARDS 44 7.1. HUMAN 44 7.2. AQUATIC 44 8. RISK ASSESSMENT 45 8.1. CARCINOGENICITY 45 8.1.1. Inhalation 45 8.1.2. Oral 45 8.1.3. Other Routes. . . 45 8.1.4. Weight of Evidence 45 8.1.5. Quantitative Risk Estimates 45 8.2. SYSTEMIC TOXICITY 46 8.2.1. Inhalation Exposure 46 8.2.2. Oral Exposure 46 ------- TABLE OF CONTENTS (cont.) Page 9. REPORTABLE QUANTITIES 48 9.1. BASED ON SYSTEMIC TOXICITY 48 9.2. BASED ON CARCINOGENICITY 48 10. REFERENCES 52 APPENDIX A: LITERATURE SEARCHED 64 APPENDIX B: SUMMARY TABLE FOR ENDOTHALL 67 APPENDIX C: DOSE/DURATION RESPONSE GRAPH(S) FOR EXPOSURE TO ENDOTHALL 68 xl ------- LIST OF TABLES No. Title Page 4-1 Median Response Concentration for F1sh and Amphibians Exposed to Endothall 14 4-2 Median Response Concentration for Invertebrates Exposed to Endothall 22 6-1 Mutagen1c1ty and Genotoxldty Summary Table for Endothall . . 40 9-1 Toxldty Summary for Oral Exposure to Endothall Using the Beagle Dog. 49 9-2 Composite Scores for Endothall Ion Using the Dog 50 9-3 Endothall: Minimum Effective Dose (MED) and Reportable Quantity (RQ) 51 ------- LIST OF ABBREVIATIONS ADI Acceptable dally Intake ATP Adenoslne trlphosphate BCF B1oconcentrat1on factor BR B1oaccumulat1on ratio BSP Bromosulfophthaleln bw Body weight CAS Chemical Abstract Service DUEL Drinking water exposure level ECso Concentration effective to 50% of recipients (and all other subscripted concentration levels) GSH Reduced glutathlone HA Health Advisory 150 Median Inhibition concentration Koc Soil sorptlon coefficient standardized with respect to organic carbon Kp Sediment-water partition coefficient LCso Concentration lethal to 50% of recipients (and all other subscripted dose levels) LD5Q Dose lethal to 50% of recipients NOAEL No-observed-adverse-effect level NOEL No-observed-effect level ppm Parts per million RfD Reference dose RQ Reportable quantity RVd Dose-rating value RVe Effect-rating value SGOT Serum glutamlc oxaloacetlc transamlnase SGPT Serum glutamlc pyruvlc transamlnase X111 ------- 1. INTRODUCTION 1.1. STRUCTURE AND CAS NUMBER Endothall Is currently referred to by CAS as 7-oxab1cyclo[2.2.l]heptane- 2.3-d1carboxyl1c acid (SANSS, 1987). Endothall 1s also known as endothal and 3,6-endo-epoxycyclohexane-1,2-d1carboxyl1c add (WSSA, 1983). Trade- names Include Accelerate. Aquathol K, Des-1-cate, Herbicide 273 and Hydrothol 191 (Melster, 1988). Discontinued names Include Hydout, Hydro- thol, Hydrothol 47 and Nlagrathal (Melster, 1988). The structure, CAS Registry number, empirical formula and molecular weight for this compound are as follows: H 0 ^CHCOOH 9 H2C | CHCOOH H CAS number: 145-73-3 Empirical formula: CgH1Q05 Molecular weight: 186.16 1.2. PHYSICAL AND CHEMICAL PROPERTIES Endothall, which 1s available as a hydrate, 1s a white or colorless solid at room temperature (Martin and Worthing, 1979; Worthing and Walker, 1983). It 1s soluble 1n water, acetone, dloxane, methanol, Isopropanol and ether (Worthing and Walker. 1983; Hartley and Kldd, 1983). It 1s noncorroslve to metals and 1s nonflammable (Worthing and Walker, 1983). Selected physical and chemical properties are as follows (Worthing and Walker. 1983; WSSA, 1983; Relnert and Rodgers, 1984): Melting point: 144°C Boiling point: not available 0168d -1- 04/19/89 ------- Vapor pressure: not available Water solubility at 20°C: 100,000 mg/l Log Kow: 1.91 pKal: 3.4 pKa2: 6.7 Density at 20°C: 1.431 g/cm3 The hydrate of endothall forms Its anhydride at 90°C. It 1s a dibasic acid and forms water soluble amlne and alkali metal salts. It 1s stable In acids. Of the three stereolsomers of this chemical, the endocls Isomer Is the most effective herbicide (Worthing and Walker, 1983). 1.3. PRODUCTION DATA Pennwalt Corporation In Wyandotte, MI, 1s the only domestic manufacturer of endothall (SRI, 1987; USITC, 1987). It 1s made by the D1els-Alder condensation of furan and malelc anhydride (Worthing and Walker, 1983). Data pertaining to the amount of endothall produced or used 1n the United States were not located In the available literature. 1.4. USE DATA The sodium, potassium and amlne salts of endothall are used as pre- emergence and postemergence herbicides, turf herbicides, aquatic herbicides, alglddes, desslcants for alfalfa and clover, and cotton harvest aids (Worthing and Walker, 1983; WSSA, 1983; Melster, 1988). 1.5. SUMMARY Endothall (145-73-3) 1s a colorless or white solid at room temperature (Martin and Worthing, 1979; Worthing and Walker, 1983). It 1s soluble In common organic solvents and soluble 1n water (Worthing and Walker, 1983; Hartley and Kldd, 1983). Pennwalt Corp. In Wyandotte. MI, 1s the only current domestic manufacturer of this compound (SRI, 1987; USITC, 1987). 0168d -2- 04/19/89 ------- Its current U.S. production volume Is not available. Various formulations of endothall are used as preemergence and postemergence herbicides, turf herbicides, aquatic herbicides and alglddes, deslccants for alfalfa and clover, and cotton harvest aids (Worthing and Walker, 1983; WSSA, 1983; Melster, 1988). Tradenames Include Accelerate, Aquathol K, Des-1-cate, Herbicide 273 and Hydrothol 191 (Melster, 1988). 0168d -3- 06/22/89 ------- 2. ENVIRONMENTAL FATE AND TRANSPORT PROCESSES 2.1. AIR 2.1.1. Chemical Degradation. Endothall Is stable to photolysis (Relnert and Rodgers, 1984). Pertinent data regarding other chemical degradation processes 1n the atmosphere were not located In the available literature cited 1n Appendix A. 2.1.2. Physical Removal Processes. A "negligible" vapor pressure for endothall (Slmslman et al., 1976) suggests that this compound may not exist 1n the vapor form 1n the atmosphere (Elsenrelch et al., 1981). Dry deposi- tion of aerosols containing endothall may be an Important removal process. The relatively high water solubility of endothall suggests that this compound may also be removed from the atmosphere by wet deposition. 2.2. WATER 2.2.1. Chemical Degradation. Endothall 1s stable to oxidation, hydroly- sis and photolysis (Relnert and Rodgers, 1984; Relnert et al., 1988). 2.2.2. Volatilization. Using the method of Nine and Mookerjee (1975), Henry's Law constant for endothall has been estimated to be ~3xlO~12 atm-m3/mole at 25°C. This value of Henry's Law constant suggests that volatilization of endothall from water surfaces would be an Insignificant fate process. 2.2.3. Adsorption. Relnert and Rodgers (1984) determined the sediment/ water partition coefficient (Kp) for endothall (dlpotasslum salt) 1n two different sediment/water systems. Sediment obtained from Pat Mayse Lake 1n northeastern Texas was predominantly sand with 0.683% organic carbon content, and sediment obtained from Roselawn Cemetery Pond In north central Texas was predominantly clay with 1.29% organic carbon content. Endothall was added to the systems at concentrations that ranged between 2.0 and 6.3 0168d -4- 04/19/89 ------- mg/l. After equilibration between the phases was achieved, the mean Kp value for endothall was determined to be 0.937 1n the lake water system and 1.42 1n the pond water system. These values corresponded to K values of 137 and 110, respectively. Analysis of data obtained by S1ms1man and Chesters (1975) using sediment/water samples from Lake Tomahawk 1n southern Michigan Indicate that endothall had K values ranging between 2.7 and 6.0. These experimental data Indicate that adsorption to suspended solids and sediments 1n water should play a relatively minor role 1n the fate of endothall In aquatic systems. 2.2.4. Persistence. Blodegradatlon and blotransformatlon are the dominant removal processes for endothall 1n aquatic systems (Relnert and Rodgers, 1984; S1ms1man et al., 1976). Endothall (dlpotasslum salt) at an Initial concentration of 0.41 mg/l was applied to a recreational area 1n Pat Mayse Lake, an ol1gomesotroph1c lake In northeast Texas. Subsequent monitoring data Indicated that endothall had a half-life of 0.33 days (Relnert et al., 1988). Dilution may have played an Important role In the reduction of the herbicide level 1n the treated area, since only a portion of the water body (1.7% of total surface area) was treated and transport from treated to nontreated areas was possible. S1kka and Rice (1973) studied the persistence of endothall (dlpotasslum salt) 1n pond water, both In aquaria and under field conditions. In a pond treated to give concentra- tions of 2 mg/i endothall, serial samples were taken and nondetectable levels were found 1n the water and top 1 Inch of the hydrosoll (sediment) 36 days after treatment. In the aquaria treated to give concentrations of 2 and 4 mg/l endothall, 50% loss 1n concentration was observed In ~4 days, with nondetectable levels existing after 7 days. In autoclaved pond water, no degradation of endothall had occurred after 9 days; however, 1 day after application 6.9% of the radlolabeled endothall appeared In the sediment. 0168d -5- 04/19/89 ------- Figures 2-1 and 2-2 show the respective disappearance patterns of endothall from the pond and aquaria. In other pond studies carried out under field conditions, the half-life for the disappearance of endothall (dlpotasslum salt) was found to range between 4.1 and 12 days (Relnert and Rodgers, 1987; Holmberg and Lee, 1976; Langeland and Warner, 1986). Both the dlpotasslum and the dlamlne salts persisted <7 days when used In Gatan Lake, Panama (Relnert and Rodgers, 1987). When static greenhouse experimental pools were treated with endothall (dlpotasslum salt) at levels of 0.03, 1.6 and 4.5 mg/i, the average half-life of this compound was determined to be 4.01 days (Relnert et al., 1985). The pools contained water, sediment and Eurasian watermllfoll. In a laboratory static shake flask study, Relnert et al. (1986) studied the blotransformatlon and blodegradatlon of endothall (dlpotasslum salt) at levels of 0.5, 2.0 and 4.0 mg/l In water samples obtained from Pat Mayse Lake (In Texas). Based on the evolution of radlo- labeled-CO-, a first-order blotransformatlon rate coefficient of 0.083 days'1 and half-life for blotransformatlon of 8.45 days were calculated. In various field studies, endothall (dlpotasslum salt) was found to persist In sediment between 0 and 7 days, while the amlne salt has been shown to persist for >21 days (Relnert and Rodgers, 1987). It has also been shown that a reduction of the dissolved oxygen content of water could have a significant effect on the degradation of endothall. In a simulated lake Impoundment, 72% of added endothall persisted 1n water for 30 days because of prolonged anoxlc conditions following weedklll. Rapid disappearance occurred only after restoration of oxygenated conditions (S1ms1man et al., 1976). Short-term Incubation of 14C-endothall with an Arthrobacter sp_., Isolated from sediment revealed that 14C was Incorporated Into glutamlc, aspartlc and citric adds and to a lesser extent alanlne, phosphate esters (not positively Identified) and other unidentified compounds. 0168d -6- 04/19/89 ------- 2.00- WATER HVDROSOIL Q46 24 28 32 36 40 44 DAYS AFTER TREATMENT FIGURE 2-1 Endothall Residues 1n Water and the Top 1-Inch of Hydrosoll of a Treated Farm Pond, with Time. (The bars represent the range of duplicate values.) Source: S1kka and R1ce, 1973 0168d -7- 04/11/89 ------- • • WATER-4ppm » * WATER-2 ppm «..—_« MYDROSOIU- 4 ppm •——•• MYOfiOSOIL- 2 ppm 12 16 20 24 28 0*VS AFTER TREATMENT FIGURE 2-2 Endothall Residues In Water and Hydrosoll of Aquaria Treated with 2 and 4 ppm of the Herbicide. (The bars represent the range of duplicate values.) Source: S1kka and R1ce, 1973 0168d -8- 04/11/89 ------- I40-glutam1c acid accounted for a large proportion of the 14C assimi- lated Into the cells. Apparently, radlolabeled C was Incorporated Into glutamlc acid by the trlcarboxyllc add cycle and an alternate, unknown pathway following Initial splitting of the oxablcyclo ring {Slkka and Saxena, 1973). 2.3. SOIL 2.3.1. Chemical Degradation. Chemical degradation processes are not expected to contribute significantly to the loss of this compound from soil (Slmslman et al., 1976). 2.3.2. Volatilization. The relatively high water solubility and negligible vapor pressure of endothall suggest that volatilization from soil surfaces would not be a significant fate process. 2.3.3. Persistence. As In aquatic environments, degradation of endothall 1n soil appears to be due primarily to mlcroblal activity. Mlcroblal degra- dation rather than chemical degradation 1s evidenced by the observations that 1) reduction of soil moisture and temperature markedly reduced endothall degradation, 2) treatment of soils with nonlabeled endothall and nutrients followed by labeled endothall led to Increased degradation compared with samples not similarly pretreated, and 3) addition of mlcroblal Inhibitors, such as pentachlorophenol, to soil reduced degradation {Slmslman et al., 1976; Tweedy and Houseworth, 1976). Endothall reportedly persists 2-7 weeks 1n soil (Tweedy and Houseworth, 1976). Approximately 70% of 14C-endothall added to an Ontario soil was evolved as 14CO? In 7 days; the remaining endothall existed 1n a nonextractable form, probably no longer as endothall (Slmslman et al., 1976). On a clay loam soil, an 85% loss of 14C-endothall was observed In 14 days. Slower rates were observed 1n 0168d -9- 04/19/89 ------- sandy soil, which may have had a higher organic content than did the clay loam, resulting 1n greater adsorption and slower degradation (Slmslman et al., 1976). 2.3.4. Adsorption. Experimentally determined K values of 2.7-137 (see Section 2.2.3.) Indicate high mobility 1n soil (Swann et al., 1983). However, fairly rapid degradation 1n the soil column Is expected to limit the extent of leaching. Nevertheless, some potential exists for groundwater contamination. 2.4. SUMMARY If released to the atmosphere, endothall 1s expected to exist predomi- nantly 1n aerosol form and may be removed by either wet or dry deposition. Photolysis 1s not expected to be an environmentally relevant fate process (Relnert and Rodgers, 1984). If released to soil or water, endothall would be subject to rapid blodegradatlon under appropriate conditions. Field and laboratory studies Indicate that endothall generally has a half-life of <1 week In surface waters under aerobic conditions (Slmslman et al., 1976; Relnert et al., 1985, 1986, 1988; Slkka and R1ce, 1973; Relnert and Rodgers, 1987; Holmberg and Lee, 1976; Langeland and Warner, 1986). This compound blodegrades more slowly 1n water under anaerobic conditions and has a half-life of ~2 months (Slmslman et al., 1976). Arthrobacter s_£., Isolated from sediment, metabolized 14C-endothall under aerobic conditions and Incorporated the 14C Into glutamlc, aspartlc and dtrlc adds, and to a lesser extent alanlne, phosphate esters (not positively Identified) and other unidentified compounds (Slkka and Saxena, 1973). Endothall 1s not expected to degrade chemically, volatilize or adsorb significantly 1n water or soil (Relnert and Rodgers, 1984; Relnert et al., 1988; Slmslman and Chesters, 1975; Swann et al., 1983). The blodegradatlon half-life of this 0168d -10- 04/19/89 ------- chemical 1n soil 1s <7 days and H Is expected to persist more In soils with high adsorption capability. Rapid blodegradatlon 1s expected to limit the extent of leaching through soil. 0168d -11- 04/19/89 ------- 3. EXPOSURE The most common route of human exposure to endothall 1s probably dermal contact by workers Involved In the manufacture, handling or application of the herbicide (HSDB, 1988). The general public could potentially be exposed by Ingestlon of contaminated crops. Monitoring data for endothall In environmental media (air, water, soil and food) were not located In the available literature cited 1n Appendix A. 0168d -12- 04/11/89 ------- 4. ENVIRONMENTAL TOXICOLOGY 4.1. AQUATIC TOXICOLOGY 4.1.1. Acute Toxic Effects on Fauna. The acute toxlclty of a variety of endothall products to fish and one amphibian are presented In Table 4-1. These data reveal that the potassium and sodium salts of endothall are the forms least toxic to aquatic vertebrates. Typical 96-hour LC5Qs for fish exposed to the dlsodlum salt were 102 mg/l for blueglll sunflsh, Lepomls macrochlrus {Inglls and Davis, 1973), 105 mg/l for redslded shiner, Notropls umbratnis, and 125 mg/i for redear sunflsh, Lepomls mlcrolophus (Folmar, 1977). Typical 96-hour LC5Qs for fish exposed to the potassium salt were 440 mg/l for blueglll sunflsh (Mayer and Ellersleck, 1986) and 372 mg/B. for goldfish, Carraslus auratus (Berry, 1984). Amlne and copper salts generated 96-hour LC5Qs of <1 mg/l. Inglls and Davis (1973) reported that water hardness did not Influence the toxldty of the dlsodlum or dlamlne salt to blueglll sunflsh. Mayer and Ellersleck (1986) demonstrated that pH was not a factor affecting the toxlclty of Aquathol K to blueglll sunflsh, but that an Increase In the test temperature from 7 to 24°C Increased the toxlclty of Aquathol K 5-fold. In the only study In which the toxlclty of an endothall product to an amphibian was assessed, Mayer and Ellersleck (1986) reported a static acute 96-hour LC5Q of 1.2 mg/i for Fowler's toad, Bufo woodhousel fowlerl. exposed to Hydrothol 191. The acute toxlclty of a variety of endothall products to aquatic Invertebrates 1s presented 1n Table 4-2. The potassium and sodium salts were less toxic to aquatic Invertebrates than other endothall salts, as they were to aquatic vertebrates. Mayer and Ellerselck (1986) reported a 96-hour LC50 ^or scud» Gammarus fasdatus, exposed to the potassium salt of 313 mg/l, 0168d -13- 04/19/89 ------- TABLE 4-1 Median Response Concentrations for Fish and Anphtblans Exposed to Endothall CO 0. Species Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh .[_, Lepomls macrochlrus 1 Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh o Lepomls nacrochlrus ^ Blueglll sunflsh ^ Lepomls macrochlrus Median Response Concentration* Chemical dlsodlum salt (liquid formulation) dlsodlum salt (granular formulation) dlamlne salt dlamlne salt dlsodlum salt (19. 2X liquid formulation) dlsodlum salt (19. 2X liquid formulation) dlsodlum salt (19. 2X liquid formulation) dlamlne salt dlamlne salt dlamlne salt dlamlne salt dlamlne salt dlamlne salt dlamlne salt Test Method static. unmeasured static. unmeasured static. unmeasured static. unmeasured static, unmeasured static. unmeasured static. unmeasured static. unmeasured static, unmeasured static, unmeasured static, unmeasured static. unmeasured static. unmeasured static. unmeasured 24-Hour 450 ppm a.e. 650 ppm a.e. 1.12 ng/t (1.06-1.19) 0.90 ng/t (0.85-0.95) 277 ng/t (234-328) 249 ng/t (222-279) 280 ng/t (242-324) 0.91 ng/t (0.79-1.05) 0.84 ng/t (0.76-0.92) 0.78 ng/t (0.72-0.84) 0.88 ng/t (0.81-0.96) 1.02 ng/t (0.95-1.10) 0.87 ng/t (0.79-0.95) 1.49 ng/t (1.21-1.83) 48 -Hour 280 ppm a.e. 280 ppm a.e. 1.03 ng/t (0.95-1.11) 0.90 ng/t (0.85-0.95) 219 ng/t (198-242) 181 ng/t (166-197) 196 ng/t (178-215) 0.63 ng/t (0.56-0.71) 0.78 ng/t (0.72-0.87) 0.68 mg/t (0.62-0.75) 0.84 mg/t (0.77-0.91) 0.80 mg/t (0.72-0.88) 0.87 mg/t (0.78-0.96) 1.34 mg/t (1.17-1.53) 96 -Hour NR NR NR NR 140 ng/t (126-156) 105 ng/t (88-125) 102 ng/t (84-124) NR NR NR NR NR NR NR Comments hardness = 29 mg/t hardness <= 29 ng/t temperature = 24'C hardness = 368.4 mg/t temperature = 24*C hardness = 368.4 ng/t temperature = 24*C hardness = 52.2 mg/t temperature = 24*C hardness = 208.7 mg/t temperature = 24'C hardness = 365.2 mg/t temperature = 24'C hardness = 52.5 mg/t temperature = 24*C hardness =52.5 ng/t temperature = 24°C hardness =210 mg/t temperature = 24'C hardness = 210 ng/t temperature <= 24'C hardness = 368.4 mg/t temperature = 24'C hardness = 368.4 mg/t temperature = 24'C hardness = 52.5 mg/t Reference Hughes and . Davis. 1965 Inglls and Davis. 1973 Inglls and Davis, 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis, 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 00 10 ------- TABLE 4-1 (cont.) o —1 00 CL 1 I O CO Median Response Concentration* Species Blueglll sunflsh Lepomls macrochlrus Blueglll sunftsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomts macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Chemical dlamlne salt dlamlne salt dlamlne salt dlpotasslum salt cocoamlne salt cocoamlne salt dlsodlum salt (liquid formulation) dlsodlum salt dlsodlum salt dlsodlum salt (liquid formulation) dlsodlum salt dlsodlum salt (granular formulation) dlsodlum salt (granular formulation) copper salt (25X wet table powder) Test Method static. unmeasured static, unmeasured static. unmeasured static static static static static static static static static static static 24-Hour 1.09 mg/t (1.01-1.18) 1.02 mg/t (0.94-1.10) 1.02 mg/t (0.94-1.11) 428 mg/t 0.8 mg/t 0.3 mg/t NR NR NR NR NR NR NR 6.70 mg/t (5.33-8.46) 48-Hour 1.02 mg/t (0.96-1.09) 0.94 mg/t (0.90-0.98) 1.00 mg/t (0.92-1.08) 268 mg/t 0.8 mg/t 0.3 mg/t NR NR NR 450 mg/t NR NR 650 mg/t NR 96-Hour NR NR NR NR NR NR NR 180 mg/t NR 280 mg/t 125-150 mg/t NR 280 mg/t 3.33 mg/t (2.51-4.4) Comments temperature •= 24*C hardness = 52.5 mg/t temperature 24°C hardness = 210 mg/t temperature 24*C hardness =210 mg/t NC NC NC no observed effect at 50 mg/t after 72 hours or at 100 mg/t after 12 days soft water 6-hour LCso = 160 mg/t In hard water NC NC no observed effect at 100 mg/t after 21 days NC temperature = 18*C hardness =135 mg/t Reference Inglls and Davis, 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Folraar. 1977 Folmar. 1977 Folmar. 1977 Folmar. 1977 Folmar. 1977 Folmar. 1977 Folmar. 1977 Folmar. 1977 Folmar. 1977 Folmar, 1977 Mayer and Filers leek. 1986 ------- TABLE 4-1 (cont.) Median Response Concentration* Species Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Leporols macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunftsh Lepomls macrochlrus Blueglll sunflsh Leporols macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomls macrochlrus Blueglll sunflsh Lepomts roacrochlrus Blueflll sunflsh Leporols macrochlrus Chemical Endothall Herbicide 282 (67. 9X liquid concentrate) Hydrothol 191 (53X liquid concentrate) potassium salt (40. 3X liquid concentrate) Endothall (17. 5X granular formulation) Aquathol K (40. 3X liquid Aquathol K (40. W liquid Aquathol K (40. 3X liquid Aquathol K (40. 3X liquid Aquathol K (40. 3X liquid Aquathol K (40. 3X liquid Aquathol K (40. 3X liquid Aquathol K (40. 3X liquid Aquathol K (40. 3X liquid concentrate) concentrate) concentrate) concentrate) concentrate) concentrate) concentrate) concentrate) concentrate) Test Method static static static static static static static static static static static static static 24-Hour 1.25 mg/t 1.15 mg/t >580 mg/t >10 mg/t >1000 >1000 >1000 >1000 >1000 >2000 >1000 >2000 mg/t mg/t mg/l mg/t mg/t mg/t mg/t mg/l 1830 mg/t (1560-2150) 48-Hour NR NR NR NR NR (867-1320) NR (1010-2550) NR NR NR NR NR NR NR 96-Hour 1.20 mg/t 0.94 mg/t 440 mg/t NR 1070 mg/t 1600 mg/t 1050 mg/t (798-1380) 1030 mg/t (845-1260) 975 mg/t (773-1230) 1740 mg/t (1410-2150) 1600 mg/t (1010-2550) 970 mg/t (840-1120) 343 mg/t (308-383) Comments temperature = hardness = 44 temperature = hardness = 44 temperature = hardness = 44 temperature = hardness = 40 temperature = hardness = 44 pH = 6.5 temperature = hardness = 44 pH = 7.5 temperature •= hardness = 44 pH = 8.0 temperature = hardness = 44 pH <= 8.5 temperature = hardness = 44 pH = 9.5 temperature = hardness = 44 temperature = hardness = 44 temperature = hardness = 44 temperature = hardness = 44 24°C mg/t 24"C mg/t 24°C mg/t 22BC mg/t 12«C mg/l 12°C mg/t 12°C mg/t 12«C mg/l 12«C mg/l 7*C mg/l 12°C mg/l 17°C mg/l 22°C rog/l Reference Mayer and Ellersleck. Mayer and Ellersleck. Mayer and Ellersleck. Mayer and Ellersleck. Mayer and Ellersleck, Mayer and Ellersleck, Mayer and Ellersleck, Mayer and Ellersleck, Mayer and Ellersleck. Mayer and Ellersleck. Mayer and Ellersleck. Mayer and Ellersleck, Mayer and Ellersleck, 1986 1986 1986 1986 1986 1986 1986 1986 1986 1986 1986 1986 1986 ------- TABLE 4-1 (cont.) 0 03 O. 1 — J 1 O •x. ^k Median Response Concentration* Species Redear sunftsh Lepomls mlcrolophus Redear sunflsh Lepomls mlcrolophus Redear sunflsh Lepomls mlcrolophus Green sunflsh Lepomls cyanellus Green sunflsh Lepomls cyanellus Redear sunflsh Lepomls mlcrolophus Redear sunflsh Lepomls mlcrolophus Redear sunflsh Lepomls mlcrolophus Redear sunflsh Lepomls mlcrolophus Carp Catfish Ictalurus punctatus Catfish Ictalurus punctatus Catfish Ictalurus punctatus Catfish Ictalurus punctatus Catfish Ictalurus punctatus Chemical monoamlne salt monoamlne salt monoamlne salt copper salt (25* wet table powder) dlsodlum salt (granular formulation) dlamlne salt dlamlne salt dlamlne salt dlsodlum salt acid dlsodlum salt (liquid formulation) dlsodlum salt (granular formulation) endothall (17. 5X granular formulation) Hydrothol 191 (53X liquid concentrate) Aquathol K (40. 3X liquid concentrate) Test Method static. unmeasured static. unmeasured static. unmeasured static static static. unmeasured static. unmeasured static. unmeasured static NR static static static static static 24-Hour 0.81 mg/l (0.78-0.84) 0.68 mg/l (0.65-0.72) 0.73 mg/l (0.69-0.80) 1.63 mg/l (1.29-2.2) NR 0.53 mg/l (0.47-0.60) 0.56 nig/1 (0.52-0.62) 0.56 mg/l (0.52-0.62) NR NR NR NR 3.4 mg/l (2.4-4.7) 2.10 mg/l >150 mg/l 48 -Hour NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR 96 -Hour NR NR NR 1.30 mg/l (1.00-1.80) NR NR NR NR 125 mg/l 175 ppm NR NR 2.1 mg/l (1.4-2.9) 0.49 mg/l >150 mg/l Comments temperature = 24*C hardness = 52.5 mg/l temperature = 24*C hardness = 210 mg/l temperature = 24*C hardness = 368.4 mg/l temperature = 18*C hardness = 44 mg/l no observed effect at 10 mg/l after 12 days temperature = 24*C hardness = 52.5 mg/l temperature = 24°C hardness =210 mg/l temperature = 24*C hardness = 368.4 mg/l NC NC no observed effect at 100 mg/l after 72 hours no observed effect at 50 mg/l after 72 hours temperature = 22*C hardness = 40 mg/l temperature = 18*C hardness = 44 mg/l temperature 12*C hardness = 44 mg/l Reference Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Mayer and Ellersleck. 1986 Folmar. 1977 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Folmar. 1977 Plmental. 1971 Folmar. 1977 Folmar. 1977 Mayer and Ellersleck. 1986 Mayer and Ellersleck. 1986 Mayer and Ellersleck. 1986 ------- TABLE 4-1 (conft.) 0 o> 00 Q. 00 1 04/11/89 Median Response Concentration* Species Catfish Ictalurus punctatus Yellow bullhead Ictalurus nebulosus Black bullhead Ictalurus melas Goldfish hybrid Goldfish Carasslus auratus Goldfish Carasslus auratus Goldfish Carasslus auratus Goldfish Carasslus auratus Goldfish Carasslus auratus Goldfish Carasslus auratus Goldfish Carasslus auratus Goldfish Carasslus auratus Goldfish Carasslus auratus Goldfish Carasslus auratus Goldfish Carasslus auratus Chemical Aqua t hoi K (40. 3X liquid concentrate) dlsodlum salt dt sodium salt acid dlamlne salt dlanlne salt dlanlne salt dlanlne salt dlamlne salt dlamlne salt monoamlne salt monoamlne salt monoamlne salt monoamlne salt monoamlne salt Test Method static static static MR static. unmeasured static. unmeasured static. unmeasured static. unmeasured static. unmeasured static. unmeasured static. unmeasured static. unmeasured static. unmeasured static. unmeasured static. unmeasured 24-Hour >100 ng/t NR NR NR 0.86 mg/t (0.76-0.98) 1.00 ng/t (0.90-1.12) 0.82 ng/t (0.14-0.91) 1.19 ng/t (1.10-1.28) 1.17 ng/t (1.03-1.33) 1.26 ng/t (1.13-1.40) 0.81 ng/t (0.74-0.88) 1.39 ng/t (1.32-1.47) NR 0.98 ng/t (0.85-1.13) NR 48-Hour NR NR NR NR 0.80 ng/t (0.73-0.88) 0.86 ng/t (0.81-0.92) 0.80 rag/l (0.73-0.88) 0.97 mg/t (0.87-1.08) 1.03 mg/t (0.90-1.18) 1.15 mg/t (1.06-1.25) 0.78 mg/t (0.68-0.89) 1.23 mg/t (1.16-1.31) 1.50 mg/t (1.35-1.66) 0.95 mg/t (0.85-1.06) 1.38 mg/t (1.28-1.49) 96-Hour >100 mg/t 170-175 ng/t 180-185 ng/t 175 ppm NR NR NR NR NR NR NR 1.20 mg/t (1.13-1.28) NR NR NR Comments temperature = 22"C hardness = 40 mg/t NC NC NC temperature ° 24"C hardness = 52.5 mg/t temperature = 24°C hardness = 52.5 mg/t temperature = 24°C hardness = 210 mg/t temperature = 24"C hardness = 210 mg/t temperature = 24°C hardness = 368.4 mg/t temperature ° 24*C hardness = 368.4 mg/t temperature = 24*C hardness = 52.5 mg/t temperature = 24°C hardness = 52.5 rag/t temperature = 24°C hardness = 52.5 mg/t temperature = 24°C hardness = 210 mg/t temperature = 24°C hardness = 210 mg/t Reference Mayer and Ellersteck. 1986 Folmar. 1977 folmar. 1977 Plmental. 1971 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis, 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis, 1973 ------- TABLE 4-1 (cont.) M o» 00 Q. 1 hO 1 Median Response Concentration* Species Goldfish Carasslus auratus Goldfish Carasslus auratus Goldfish Carasslus auratus Goldfish Carasslus auratus Goldfish Carasslus auratus Fathead minnow Plmephales pronelas Bluntnose nlnnow Plmephales notatus Chemical nonoamlne salt nonoamlne salt monoamtne salt monoamtne salt potassium salt hydrothol 191 (53X liquid concentrate) dlsodtum salt Test Method static. unmeasured static. unmeasured static. unmeasured static. unmeasured static. unmeasured static static 24 -Hour 1.28 mg/l (1.20-1.36) 1.17 mg/t (1.04-1.21) NR 1.18 mg/l (1.09-1.28) NR 1.90 ng/t NR 48-Hour 1.18 ng/t (1.11-1.26) 1 .05 ng/t (0.93-1.18) 1.52 ng/t (1.38-1.67) 1.14 ng/t (1.08-1.21) NR NR NR 96-Hour 1.11 ng/t (1.06-1.16) NR NR 1.08 ng/t (1.02-1.14) 372 ng/t (340-406) 0.75 ng/t 110-120 mg/t Comments temperature = 24*C hardness =210 ng/t temperature = 24*C hardness = 368.4 mg/t temperature « 24'C hardness - 368.4 mg/t temperature = 24*C hardness = 368.4 mg/t temperature = 20-23°C hardness = 50 mg/t temperature = 18*C hardness = 44 mg/t NC Reference Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Inglls and Davis. 1973 Berry. 1984 Mayer and E Her sleek. 1986 Folmar, 1977 Bluntnose minnow Plraephales notatus Lake Emerald Shiner Golden shiner Notemlgonus crysoleucas dtsodtum salt (granular formulation) cocoamlne salt nonoamlne salt (53X active Ingredient) static NR flowthrough. measured NR 0.12 ppm NR Golden shiner nonoamlne salt Notemlgonus crysoleucas (53X active Ingredient) flowthrough. NR measured NR NR NR NR NR NR NR NR no observed effect at 40 mg/t after 21 days NC 120-hour LCso °-32 mg/t (0.19-0.46) hardness = 279 mg/t 120-hour LC50 1.6 mg/t (1.2-2.0) hardness - 20 mg/t Folmar. 1977 Ptmental. 1971 Flnlayson. 1980 Flnlayson. 1980 o ^ •^ CO 10 Redfln shiner Notropls lutrensls Redfln shiner Notropls lutrensls Redslded shiner Notropls umbratnis dl sodium salt dlsodtum salt (granular formulation) dtsodtum salt static static static NR NR NR NR NR NR 95 ng/t NR 105 ng/t NC no observed effect at 40 mg/t after 21 days NC Folmar. Folmar. Folmar. 1977 1977 1977 ------- TABLE 4-1 (cont.) o CO o. rs» O 1 04/11/89 Median Response Concentration* Species Redslded shiner Notropls umbratllls Smallmouth bass mlcropterus dolomleul Smallmouth bass mlcropterus dolomleul Largemouth bass Largemouth bass Hlcropterus salmoldes Hlcropterus salmoldes Hlcropterus salmoldes Hlcropterus salmoldes Striped bass Horone saxltllls Salmon Coho salmon Oncorhynchus klsutch Cutthroat trout Salmo clarfcl Rainbow trout Salmo qalrdnerl Rainbow trout Salmo qalrdnerl Rainbow trout Salmo qalrdnerl Chemical dlsodlum salt (granular formulation) dlsodlum salt (liquid formulation) dtsodtum salt acid acid dlsodlum salt dlsodlum salt dlsodlum salt dlsodlum salt (granular formulation) dlsodlum salt (15. 5X a.e.) acid Aquathol K (40. 3X liquid concentrate) Hydrothol 191 (53X liquid concentrate) copper salt dlmethylamtne salt cocoamlne salt Test Method static static static NR NR static static static static static. unmeasured NR static static NR NR static 24-Hour NR NR NR >560 ppm NR NR NR NR NR 2000 ppm (1850-2050) NR >100 mg/l 0.18 mg/t (0.12-0.27) NR NR NR 48-Hour NR NR NR NR NR NR NR NR NR 1700 ppm (1590-1820) 136 ppm NR NR 0.290 ppm 1.15 ppm 1.5 mg/t 96-Hour NR NR NR NR 120 ppm NR 200 mg/t 100-125 mg/t NR 710 ppm (634-795) NR >100 mg/l 0.18 mg/l (0.12-0.27) NR NR NR Comments no observed effect at 40 mg/t after 21 days no observed effect at 25 mg/t after 12 days no observed effect at 10 mg/t after 12 days NC NC no observed effect at 10 mg/t after 72 hours soft water NC no observed effect at 10 mg/t after 21 days temperature = 21 *C hardness = 35 ppm NC temperature = 13*C hardness = 44 mg/t temperature » 10*C hardness = 162 mg/t NC NC NC Reference Folmar, 1977 Folmar. 1977 Folmar, 1977 Plmental. 1971 Plmental, 1971 Folmar. 1977 Folmar. 1977 Folmar. 1977 Folmar. 1977 Wellborn. 1971 Plmental. 1971 Mayer and Ellersleck. 1986 Mayer and Ellersleck. 1986 Plmental. 1971 Plmental. 1971 Folmar. 1977 ------- TABLE 4-1 (cont.) o & Median Response Concentration* g Species Rainbow trout Salmo qalrdnerl Rainbow trout Salmo qalrdnerl Rainbow trout Salmo qalrdnerl Rainbow trout Salmo qalrdnerl Rainbow trout Salmo qalrdnerl Rainbow trout Salmo galrdnerl ^ Rainbow trout i Salmo qalrdnerl Rainbow trout Salrap qalrdnerl Rainbow trout Salmo qalrdnerl Harlequin fish Erlmyzon sucetta Erlmyzon sucetta Fowlers Toad Bufo woodhousel fowlerl Chemical dl sodium salt (granular formulation) Aquathol K (40. 3X liquid concentrate) Aquathol K (40. 3X liquid concentrate) copper salt (25X wet table powder) endothall (17. 5X granular formulation) Endothall DES-I-CATE (5.5X liquid concentrate) Endothall Herbicide 282 (67. 9X liquid concentrate) Hydrothol 191 (53X liquid concentrate) potassium salt (40. 3X liquid concentrate) acid phlsodlum salt (liquid formulation) dlsodlum salt (granular formulation) Hydrothol 191 (53X liquid concentrate) Test Method static static static static static static static static static NR static static static 24 -Hour NR >420 mg/t 58 mg/t (49-67) 0.35 mg/t (0.27-0.45) 2.8 mg/t (2.3-3.4) 0.50 mg/t 1.15 mg/t 0.81 mg/t >560 mg/t 565 ppm NR NR 3.2 mg/t (1.7-5.5) 48-Hour NR NR NR NR NR NR NR NR NR NR NR NR NR 96-Hour NR 230 mg/t (187-283) 32 mg/t (22-46) 0.14 mg/t (0.08-0.24) 1.8 mg/t (1.2-2.5) 0.31 mg/t 0.98 mg/t 0.56 mg/t 450 mg/t NR NR NR 1.2 mg/l (0.4-3.4) Comments no observed effect at 10 mg/t after 21 days temperature = 13*C hardness = 44 mg/t temperature = 12*C hardness = 44 mg/t temperature = 13*C hardness = 44 mg/t temperature = 12*C hardness = 40 mg/t temperature = 13"C hardness = 44 mg/t temperature = 13°C hardness = 44 m/gt temperature = 13*C hardness = 44 mg/t temperature = 13"C hardness = 44 mg/t NC no observed effect at 25 mg/l after 12 days no observed effect at 10 mg/t after 12 days temperature = 15*C hardness = 44 mg/l Reference Folmar. 1977 Mayer and Ellersleck. 1986 Mayer and Ellersleck, 1986 Mayer and Ellersleck. 1986 Mayer and Ellersleck, 1986 Mayer and Ellersleck. 1986 Mayer and Ellersleck. 1986 Mayer and Ellersleck. 1986 Mayer and Ellersleck. 1986 Plmetal. 1971 Folmar. 1977 Folmar. 1977 Mayer and Ellersleck. 1986 2 *Values In parentheses represent 95X confidence Interval -^ ^ NR = Not reported; NC = no comment; a.c. = acid equivalent ------- TABLE 4-2 Median Response Concentrations for Invertebrates Exposed to Endothall GO 0. r\J ro i 0 ^^ ^v «^n Median Response Concentration* Species Aquatic saw bugs Asellus conrounls Scud Gammarus fasclatus Scud Ganmarus fasclatus Scud Gamtnarus fasclatus Scud Gamrearus lacustrls Scud Gammarus lacustrls Scud Gamrearus lacustrls Scud Gamaarus lacustrls Scud Hyallela azteca Seed shrimp Cypretta kawatal Shrimp Palaemonetes kadlakensts Midge Chlronlmus tentans Chemical dlpotasslum salt cocoamlne salt potassium salt (40. W liquid concentrate) Hydrothol 47 (66. 7X liquid concentrate) dlpotasstum salt endothall dlsodlum salt Hydrothol 191 (53X liquid concentrate) dlpotasslum salt monohydrate acid (99.9X) Hydrothol 191 (53X liquid concentrate) monohydrate acid (99.9X) Test Method flowthrough flowthrough static static NR NR static static flowthrough static static static 24 -Hour NR 3.1 ng/t 313 mg/l 1.50 Bg/t (0.53-4.2) >100 ppm 2 ppm NR 2.00 mg/t (1.6-2.7) NR 180 mg/t (141-230) >0.10 ng/ft 354 mg/l (161-780) 48-Hour NR 2.1 mg/t NR NR NR NR NR NR NR NR NR NR 96 -Hour NR 0.48 mg/t 313 mg/t 0.51 ng/t (0.28-0.95) NR NR >320 ppm 0.5 mg/t (0.37-0.67) NR NR 0.05 mg/t (0.02-0.12) NR Comments temperature = 17°C effective concentration >10 ppm after 120 hours NC .temperature = 21 *C hardness = 44 mg/t temperature = IS'C hardness = 272 mg/t NC NC temperature = 59°F temperature = 21*C hardness = 272 mg/t temperature = 17°C effective concentration >10 ppm after 120 hours 72-hour ECso =123 mg/t (89.9-168) temperature = 21 °C hardness = 272 mg/t 72-hour ECso = 151 (112-203) Reference U1 11 lams et al., 1984 Folroar. 1977 Mayer and Ellersleck. 1986 Mayer and Ellersleck. 1986 Plmental. 1971 Plmental. 1971 Nebeker and Gaufln. 1964 Mayer and Ellersleck. 1986 Williams et al., 1984 Hansen and Kawatskl. 1976 Mayer and Ellersleck. 1986 Hansen and Kawatskl. 1976 ------- TABLE 4-2 (cont.) 0 co Species n. Stonefly Pteronarcys callfornlca Water flea Daphnla maqna Clams Hercenarla nercenarla Median Response Concentration* Chemical hydrothol 191 (53X liquid concentrate) acid dl sodium salt Test Method 24-Hour static 5.75 mg/t static 46 ppn (36-57) static NR 48-Hour 3.25 mg/t NR 50 mg/l 96-Hour NR NR NR Comments temperature = 15*C hardness = 44 mg/l 26-hour median Immobili- zation concentration NC Reference Mayer and I Hers leek. 1986 Crosby and Tucker. 1966 Folmar. 1977 (eggs) Clams Hercenarla mercenarla (larvae) Oyster Crassostrea vlrglnlca dlsodlm salt dlsodtum salt static static NR NR NR NR NR NR effective concentration >10 mg/t after 10 days effective concentration >25 mg/t after 12 days Folmar. 1977 Folmar. 1977 to *Values In parentheses represent 95X confidence Interval NC «= No comment; NR = not reported 03 vO ------- Nebeker and Gaufln (1964) generated a 96-hour LC5Q for scud exposed to the dlsodlum salt of >320 ppm. The 96-hour LC5Q for scud exposed to a mono- N,N-d1methyl cocoamlne salt formulation was 0.48 mg/l (Folmar, 1977). The 26-hour median Immobilization concentration for Daphnla maqna exposed to the acid was 46 ppm (Crosby and Tucker, 1966). Folmar (1976, 1978) assessed the avoidance response of rainbow trout (£. galrdnerl) fry and mayfly (Ephemerella walkerl) nymphs to the dlpotasslum salt of endothall. Organisms were placed 1n a flowthrough Y-shaped avoid- ance maze 15 minutes before the Introduction of endothall; the distribution of organisms between each arm was recorded after 1 hour. The Investigator reported that neither trout nor mayflys avoided endothall at the highest concentration tested (10 mg/a, active Ingredient). 4.1.2. Chronic Effects on Fauna. 4.1.2.1. TOXICITY -- L1gour1 et al. (1983) assessed the effects of endothall on juvenile Chinook salmon, Onchorynchus tshawytscha. Fish were exposed to endothall 1n 160-1 glass aquaria that received lake water at a flow rate of 1 l/mln, resulting 1n a complete turnover of test solution every 5 hours. Endothall solutions were dripped Into test aquaria from MaMott flasks at a rate of 1 mi/m1n. Water temperature was maintained at ~16°C. Endothall concentrations were measured on the first and eighth days of the assays. The Investigators reported a nominal 14-day LC5Q (and 95% cofldence limits) of 62.5 ppm (53.4-73.1) as the acid equivalent (88.2% ppm of Aquathol K). Surviving fish exposed to lower concentrations of endothall demonstrated poor survival when transferred to seawater during a recovery period. F1sh exposed to >3 ppm endothall for 14 days experienced 80-100% mortality within 4 days when transferred to seawater. Conversely, fish transferred to freshwater demonstrated high levels of survival (>80%) following 14 days of exposure to <55 ppm endothall. 0168d -24- 04/19/89 ------- 4.1.2.2. BIOACCUMULATION/BIOCONCENTRATION — S1kka et al. (1975) monitored the uptake of 14C-endothall by blueglll sunflsh, L. macrochlrus. F1sh were exposed to 2 ppm 14C-endothall 1n 500 ml of solution for 96 hours, or by force-feeding encapsulated 14C-endothall at a rate of 10 mg endothall/kg bw. The quantity and distribution of 14C 1n force-fed fish was determined 48 hours after feeding. The Investigators reported that <1% of the total amount of herbicide was taken up by fish from water. Fish fed [14C]endothall eliminated 73% of the administered dose 1n the 48 hours after feeding. The Investigators found no evidence suggesting that bluegllls are capable of metabolizing endothall. Isensee (1976) assessed the bloaccumulatlon potential of endothall In aquatic model ecosystems. Tests were conducted In glass tanks containing 4 i of water. Before the establishment of test microcosms, soil to be used as substrate 1n the system was treated with 14C-endothall. The system was Inoculated with Daphnla magna. snails (Physa). algae (Oedogonlum cardlacum) and 10 ml of old aquarium water containing a variety of diatoms, protozoa and rotifers. After 30 days, 2 mosqultoflsh were added to the tanks and all organisms were harvested 3 days later. BR values were based on the ratio of 14C In tissue versus that 1n water. The Investi- gators reported BR values of 63, 36, 150 and 10 for algae, snails, daphnlds and fish, respectively. Serns (1977) reported that endothall levels 1n tissues of bluegllls from a pond treated with 5.0 mg/9. potassium endothall were not detectable (<0.01 mg/i) 3 days after treatment of the pond, despite water levels of 4.9-3.4 mg/8. from days 3-10 after treatment. Residue levels of 0.02 and 0.04 mg/l were found In fish tissues 2 hours and 1 day, respectively, after treatment of the pond. Measured concentrations of endothall In the water column for those time periods were 6.2 and 4.9 mg/i, respectively. 0168d -25- 04/19/89 ------- Relnert and Rodgers (1986) conducted field trials In Texas to validate models attempting to predict the fate of dlpotasslum endothall In natural ponds. They also attempted to estimate fish BCFs from caged blueglll sunflsh, L.. macrochlrus. held 1n ponds treated with 2 mg/a. The Investi- gators reported a lack of endothall residues 1n tissues of fish held 1n treated ponds 7 days after the Initiation of treatment. They estimated BCF values of 0.65-1.05 for fish from regression equations using a water solubility of 1228 g/i and a log KQW of 0.132. 4.1.3. Effects on Flora. 4.1.3.1. TOXICITY -- Walsh (1972) assessed the effects of the add and amlne and dlpotasslum salts of endothall on photosynthesis and growth of four species of marine algae, Chlorococcum sp., Dunallella tertlolecta. Isochrysls galbana and Phaeodactylum tMcornutum. Effects on photosynthesis were determined by monitoring oxygen evolution from log phase growth cultures In the presence of endothall at I0-m1nute Intervals for 90 minutes on a photosynthesis-model resplrometer. Effects on growth were determined after 10 days for cultures maintained at 20°C under 6000 lux Illumination with alternating 12-hour periods of light and dark. EC5Q values were calculated based on the concentration of the product, although the percent active Ingredient 1n products used was not specified. The 90-mlnute EC™ values based on photosynthesis for the four algal species exposed to the technical add were 100, 425, 60 and 75 ppm, respectively. Photosynthetlc EC,- values for the amlne and dlpotasslum salts for each species were >1000 and >5000 ppm, respectively for a 90-m1nute treatment period. Growth EC5Q values for each spedes exposed to the technical add were 50, 50, 25 and 15 ppm, respectively, after 90 minutes of treatment. Growth EC5_ values for species exposed to the amlne salt were 300, 450, 225 and 250 ppm, 0168d -26- 04/11/89 ------- respectively, after 90 minutes. Growth EC50 values for algae exposed to the dlpotasslum salt were 1500, 1500, 3000 and 500 ppm, respectively, after 90 minutes. Cain and Cain (1983) assessed the effects of exposure to the amlne salt of endothall (Hydrothol 191 as N,N-d1methylalkylam1ne salt, 53%) on zygo- spore germination and growth of the alga, Chlamydomonas moewusll. Exposure of algal cultures and zygospores to endothall was conducted on 1.5% agar plates to which endothall had been added. Plates with algal cultures were Incubated at 21°C for 7 days after Inoculation. Plates with zygospores were Incubated for 3 days. Cell counts were obtained by first rinsing algae from the surface of each plate, and then homogenizing suspensions In a micro- blender and determining absorbance readings for each suspension at 565 nm with a spectrophotometer. Growth was expressed as a percentage of the controls. Endothall concentrations were based upon concentration of the active Ingredient. The Investigators reported I5Q values of 1.7 yM for growth and 94 yM for zygospore germination. Growth of cultures at the lowest concentration of endothall tested (1 yM) was significantly different from the control cultures. The minimum alglcldal concentration was 7.5 yM as determined by growth and 9.0 yM with respect to zygospore germination. 4.1.3.2. BIOCONCENTRATION -- Relnert et al. (1988) estimated a water- milfoil, Myrlophyllum splcatum, BCF for the dlpotasslum salt of endothall from a regression equation designed for use In situations with constant exposure conditions for 96-120 hours. The equation was generated from data collected on an aquatic herbicide, several organic compounds, a floating aquatic macrophyte and log K . The Investigators estimated a BCF of 0.73 using a log KQW of 0.132. Previously, Relnert et al. (1985) and Relnert 0168d -27- 04/19/89 ------- and Rodgers (1986) reported experimental BCF values of 3.9, 12.1 and 768.9 for dlpotasslum endothall from studies conducted with milfoil 1n 1.1 m diameter greenhouse pools. The Investigators discounted the 768.9 value as unrealistic because of the Inadvertent analysis of endothall-tolerant epiphytic algae present on the milfoil. 4.1.4. Effects on Bacteria. Pertinent data regarding the effects of exposure of aquatic bacteria to endothall were not located In the available literature dted 1n Appendix A. 4.2. TERRESTRIAL TOXICOLOGY 4.2.1. Effects on Fauna. Pertinent data regarding the effects of exposure of terrestrial fauna to endothall were not located In the available literature cited 1n Appendix A. 4.2.2. Effects on Flora. Pertinent data regarding the effects of exposure of terrestrial flora to Endothall were not located 1n the available literature cited In Appendix A. 4.3. FIELD STUDIES Yeo (1970) assessed the effects of the dlsodlum or dlpotasslum salts of endothall on aquatic weeds and fish In 13 farm reservoirs and plastic growth pools (122 cm2x60 cm deep) stocked with common vegetation, smallmouth bass, green sunflsh and mosqultoflsh. Calculated Initial concentrations were <3 ppm 1n reservoirs and <4 ppm 1n growth pools. The Investigators reported that application of endothall to the reservoirs controlled a variety of pondweeds and other plants but did not affect populations of elodea, duckweed, nHella and chara. The Investigators did not observe any mortalities among the smallmouth bass, green sunflsh or mosqultoflsh. Effects on vegetation In growth pools were similar to those observed 1n reservoirs. There were no mortalities among bass and sunflsh 1n the growth 0168d -28- 04/11/89 ------- pools; several mosqultoflsh were killed, but the Investigators did not attribute the mortalities to the endothall treatment of the pools. Serns (1975) assessed the effects of the dlpotasslum salt of endothall on the zooplankton community of a 0.31 ha pond 1n Wisconsin. Control and treatment ponds were drained before treatment to eliminate existing fish populations, and were then allowed to refill from a common source. Both ponds were restocked with blueglll sunflsh at a rate of 20 males and 20 females per hectare. Dlpotasslum endothall was added to one of the ponds at a rate of 5 mg/8. (active Ingredient) at the end of May 1973, and both ponds were monitored through the end of October 1973. The Investigators reported the presence of Cladocera (Daphnla. CeModaphnla and Chydorus). cyclopold and calanold copepods, and ostracods In the treatment pond at densities equal to or greater than those found 1n the control pond at various times over the course of the study period. The Investigator concluded that there no apparent effects on zooplankton communities In the pond as a result of treatment with dlpotasslum endothall at 5 mg/fi,. Holmberg and Lee (1976) treated a 0.32 ha pond with 5.0 mg/l (active Ingredient) endothall. The Investigators monitored effects on vascular plants and caged and natural populations of blueglll sunflsh, L_. macro- chlrus. Endothall treatment effectively eliminated coontall, Ceratophyllum demersum. flat-stemmed pondweed, Potamogeton zosterlformls. sago pondweed, Potamogeton pectlnatus. milfoil, MyMophyllum splcatum, and elodea, Elodea canadensls. within 3 weeks of treatment at the recommended dosage. The treated pond was eventually taken over by chara, Chara sp. There were no mortalities among either free or caged bluegllls at the endothall treatment level of 5 mg/8. within a few weeks following treatment. 0168d -29- 04/19/89 ------- Serns (1977) reported the results of long-term observations of bluegllls exposed to endothall as part of a continuing study first reported by Holmberg and Lee (1976). Bluegllls were collected from control and treated ponds 18 months after the Initial application of 5 mg/a of endothall. Percent survival of bluegllls stocked 1n the two ponds before treatment was greater 1n the control pond than 1n the endothall-treated pond, although growth of adult bluegllls 1n the treated pond was less than that 1n the control pond. The difference was attributed to competition as a result of greater density of fish, rather than to a toxic effect from exposure to endothall. Length, weight, density and standing crop of young-of-year blue- gills spawned In both ponds during the observation period were equivalent; there were no perceptible effects on reproduction or survival of first generation bluegllls. Beckmann et al. (1984) assessed the effects of the dlpotasslum salt of endothall on the bacterial populations In gravel-pH ponds over ~4 months. Parameters measured Included total bacterial numbers In the water column and respiration rates of bacteria collected from the treated pond. Endothall was applied to the treatment pond at a target concentration of 0.3 ppm. Respiration rates were measured 1n the presence of 5 ppm endothall. The Investigators reported that endothall had no effect on total bacterial numbers present 1n the control and treated ponds and did not significantly alter respiration rates of bacteria found 1n those ponds. 4.4. AQUATIC RISK ASSESSMENT The majority of studies assessing the toxldty of endothall to aquatic organisms are not suitable for use 1n developing water quality criteria by the method of U.S. EPA/OWRS (1985). In many Instances, Investigators failed to Identify the endothall salt present In a formulation Identified only by 0168d -30- 04/24/89 ------- Us tradename, the percentage of active Ingredient 1n an endothall product, the "Inert" Ingredients 1n an endothall formulation, or the material upon which an LC5Q was calculated (formulation or active Ingredient). Criteria generated by the method of U.S. EPA/OURS (1985) do not permit the use of data generated on formulated mixtures and emulslflable concentrates. Apparently, the sodium and potassium salts are often used 1n field treatments for nuisance aquatic weed control at treament dosages of 2-5 mg/a.. The acute toxlclty of these salts appears to be >100 mg/l, suggesting a low order of toxlclty under normal use conditions. Addition- ally, experimental evidence suggests that the sodium and potassium salts of endothall are not persistent and do not bloaccumulate In aquatic organisms, thereby reducing the potential for chronic exposure. 4.5. SUMMARY The potassium and sodium salts of endothall are the forms least toxic to both aquatic vertebrates and Invertebrates, with 96-hour LC s of >100 mg/i. In contrast, 96-hour LC5Qs for the amlne and copper salts are <1 mg/i for a variety of aquatic organisms. Water hardness did not Influence the toxlclty of dlsodlum or dlamlne salts to bluegllls (Inglls and Davis, 1973) and pH did not affect the toxlclty of Aquathol K to bluegllls (Mayer and Ellersleck, 1986). The toxlclty of Aquathol K to blueglll sunflsh Increased 5-fold when the test temperature Increased from 7 to 24°C (Mayer and Ellersleck, 1986). The 14-day LC5Q of endothall to juvenile Chinook salmon, Onchorynchus tshawytscha. was 62.5 ppm (LlgouM et al., 1983). Surviving fish demon- strated poor survival when transferred to seawater but good survival when transferred to freshwater. The 10-day growth EC5Qs for various species of marine algae exposed to the amlne and dlpotasslum salts ranged from 225-3000 0168d -31- 04/11/89 ------- ppm (Walsh, 1972). No short- or long-term effects were observed among natural populations of organisms 1n ponds or reservoirs treated with <5 mg/8, endothall. Experimental evidence suggests that endothall 1s not likely to bloaccu- mulate In aquatic organisms. Slkka et al. (1975) reported that bluegllls took up <1% of the available herbicide from water over a 96-hour period. Isensee (1976) reported bloaccumulatlon ratios of 63, 36, 150 and 10 for algae, snails, daphnlds and fish. Serns (1977) was unable to detect endothall residues 1n tissues of bluegllls from a pond that had been treated 3 days earlier with endothall to give a concentration of 5 mg/l. Relnert and Rodgers (1986) were unable to detect endothall residues In tissues of bluegllls from a reservoir that had been treated 7 days earlier with 2 mg/B, endothall. Relnert et al. (1988) reported BCFs of 3.9, 12.1 and 768.9 for the dlpotasslum salt of endothall 1n watermllfoll, but discounted the highest value because of experimental errors. 0168d -32- 04/19/89 ------- 5. PHARMACOKINETICS 5.1. ABSORPTION Six adult Wlstar rats weighing 250-260 g (two males) or 172-206 g (four females) were prefect diets containing unlabeled endothall (5 ppm) for 2 weeks before single gavage administration of 14C-labeled endothall dissolved 1n 20% ethanol (5 mg/kg) (Soo et al., 1967). As Indicated 1n Section 5.4., total recovery of radioactivity 1n the feces, urine and expired CO- at 48 or 72 hours following treatment ranged from 95.7-99.1% of the administered dose. Most of the radioactivity, 84.8-91.1% of the administered dose, was excreted 1n the feces, and the balance was excreted 1n the urine (5.7-6.9%) and expired COp. Approximately 20% of the radio- activity 1n the feces was shown to be unchanged endothall, with the remainder bound In some unknown form (Section 5.3.). The Investigators presumed that the remaining radioactivity was due to an endothall conjugate. However, since bound endothall 1n the feces does not necessarily mean that the endothall was conjugated, and biliary excretion of endothall appears to be Insignificant (Section 5.4.), U seems likely that the bound endothall was unabsorbed endothall that was adsorbed onto gastrointestinal contents. Low levels of radioactivity 1n tissues other than the stomach and .Intestine and slow tissue elimination rates also seem to Indicate that only a small proportion of the administered dose was absorbed (Section 5.2.). Therefore, results of this study suggest that endothall was poorly absorbed from the gastrointestinal tract. Intestinal diffusion or secretion of endothall, however, or conjugation of endothall 1n the Intestines could have occurred. An additional nine female Wlstar rats were given 1 mg of 14C-endothall by gavage, and were killed at 1, 2, 4, 6, 8, 12, 24, 48 or 72 hours. Eleven different organs were removed and freeze-drled, and their radioactivity was 0168d -33- 04/19/89 ------- measured. Analysis of the specific radioactivity and total accumulation In each tissue Indicated that only a small proportion of the administered dose was absorbed. Peak tissue concentrations of radioactivity were found In the animal that was sacrificed 1 hour after treatment (Section 5.2.). This Indicates that absorption of endothall occurred largely within the first hour. 5.2. DISTRIBUTION Nine female Wlstar rats were given 1 mg of 14C-endothall by gavage and sacrificed at 1, 2, 4, 6, 8, 12, 24, 48 or 72 hours (Soo et al., 1967). Peak tissue concentrations of radioactivity were reached In all of 11 tissues sampled except the Intestine within 1 hour posttreatment. The radioactivity was highest 1n the stomach and Intestine (-98% of the admin- istered dose). Approximately 1% of the administered dose was found In both the liver and kidney; trace amounts were found 1n the blood, lung, heart, spleen, muscle and brain. Radioactivity was not detected 1n body fat, reflecting the hydrophlUc nature of the compound. Clearance was monophaslc from the Intestine (half-time of 14.4 hours) and liver (half-time of 21.6 hours), and blphaslc from the stomach (half-times of 2.2 and 14.4 hours) and kidney (half-times of 1.6 and 34.6 hours). No residual radioactivity was seen at 72 hours 1n any organ other than the Intestine. In order to determine the possible secretion of Ingested endothall In milk, two pregnant female rats were given unlabeled endothall (0.2 mg/day In 10% sucrose) by means of a medicine dropper for the last week of gestation, and were then given 14C-endothall (0.4 mg/day In 10% sucrose solution) for 5 days after the pups were born. Analysis of stomach contents and tissues of 12 pups of various ages showed no radioactivity, suggesting that endothall was not secreted In the milk of a lactatlng female rat. 0168d -34- 04/19/89 ------- 5.3. METABOLISM Six rats that were administered 5 mg/kg 14C-labeled endothall by gavage excreted 84.8-91.1% of the administered radioactivity 1n the feces (Soo et al., 1967) (Section 5.4.). Alcohol extraction and paper chromato- graphy of the feces showed that "20% of the fecal radioactivity was due to unchanged endothall and 80% was bound In some form (I.e., unextractable). The Investigators presumed that the latter radioactivity was due to an endothall conjugate. As biliary excretion seems to be Insignificant (Section 5.4.), U 1s likely that the bound endothall was not conjugated, although conjugation 1n the Intestine could have occurred. Urinary radio- activity accounted for 5.9-6.9% of the administered dose. The radioactivity recovered 1n the urine appeared to be unchanged endothall. A small amount of the administered radioactivity (2.6-2.8%) was converted to CO,, and expired 1n the breath. Since gastrointestinal absorption of endothall seems to be poor, It Is possible that the CO- resulted from metabolism by Intes- tinal microorganisms. There were no apparent gender-related differences 1n the fate of endothall. 5.4. EXCRETION A 5 mg/kg dose of 14C-endothall was administered to six rats by gavage (Soo et al., 1967) (see Section 5.1.). Radioactivity 1n the feces accounted for 64.5-71.2, 17.7-20.7 and 0.1-0.5% of the administered dose after 24, 48 and 72 hours, respectively. Since levels of radioactivity In the liver were not very large compared with the administered dose (see Section 5.2.), 1t was concluded that biliary excretion does not seem to be significant. Dally recovery of radioactivity 1n the urine accounted for 3.4-6.8, 0.3-0.6 and 0.1-0.2% of the administered dose after 24, 48 and 72 hours, respectively. 0168d -35- 04/19/89 ------- Less than 3% of the administered dose (2.6-2.8%) was found 1n expired CO- after 24 hours; radioactivity 1n the expired air was not detected after 48 and 72 hours. Excretion 1n the feces, urine and expired air, therefore, occurred largely 1n the first 24 hours and was essentially complete after 48-72 hours, as total recovery varied from 95-99%. Endothall was not excreted 1n the milk (see Section 5.2.). 5.5. SUMMARY Data obtained from rats of both sexes treated with a single oral dose of 14C-endothall suggest that gastrointestinal absortlon 1s poor (Soo et a!., 1967). Peak tissue concentrations occurred within 1 hour In all tissues sampled except the Intestine. The absorbed radioactivity occurred predomi- nately 1n the stomach and Intestine (~99% of the administered radioactiv- ity). About 1% of the administered radioactivity occurred 1n the liver and kidneys. Radioactivity was not found In fat or milk, and was essentially eliminated from all tissues within 72 hours. At least 85% of the adminis- tered dose was excreted 1n the feces, but ~20% of this was unchanged com- pound and 80% was bound In some form. It seems more likely that the bound form 1s endothall that Is adsorbed onto gastrointestinal contents rather than an endothall conjugate. Small quantities were excreted 1n the urine (~6%), apparently as unchanged compound, and 1n the breath as CO- (~3%). 0168d -36- 04/19/89 ------- 6. EFFECTS 6.1. SYSTEMIC TOXICITY 6.1.1. Inhalation Exposure. Pertinent data regarding the effects of Inhaled endothall were not located 1n the available literature cited 1n Appendix A. 6.1.2. Oral Exposure. 6.1.2.1. SUBCHRONIC — Rats were given 1000 or 10,000 ppm d1sodium endothall 1n the diet for 4 weeks (BMeger, 1953a). Using a body weight of 0.4 kg, a dally food consumption of 20 g, and the ratio of the molecular weight of endothall to dlsodlum endothall, these concentrations can be con- verted to equivalent doses of endothall 1on of 40 mg/kg/day and 400 mg/kg/day. At the low dose, there were slight liver degeneration and focal hemorrhaglc areas In the kidney. At the high dose, most of the rats died within 1 week. Nine male dogs (one dog per dose) were given capsules containing 1-50 mg dlsodlum endothall/kg/day (0.8-40 mg/kg/day of endothall 1on) for 6 weeks. 01 sodium endothall doses of >20 mg/kg/day resulted 1n death 1n all dogs within 11 days, and erosion and hemorrhages of the stomach (Brleger, 1953b). Congestion of the stomach and edema of the stomach and upper Intestines were common 1n all dogs. The Investigators suggested that the lesions In the stomach of dogs resulted from the administration of the undiluted test substance without food. 6.1.2.2. CHRONIC — Beagle dogs (four/sex/group) were fed 0, 100, 300 or 800 ppm dlsodlum endothall 1n the diet (equivalent to 0, 2, 6 or 16 mg endothall 1on/kg/day) for 24 months (Keller, 1965; Pennwalt Agchem, n.d.). Values for hematology, BSP clearance, SGOT, urlnalysls, weight gain and food consumption 1n treated animals were not significantly different from 0168d -37- 06/19/89 ------- controls. Relative and absolute stomach and small Intestine weights were Increased at the two higher doses, but extensive hlstopathologlcal exami- nation of rats receiving the highest dose revealed no compound-related lesions, except Increased mucosal gland activity In the stomach and slight edema In the region of the pylorls. No effects were noted at 2 mg/kg/day. No toxic effects were noted 1n female rats (strain unspecified) given <2500 ppm d1 sodium endothall 1n the diet for 2 years (equivalent to 100 mg/kg/day of the endothall 1on assuming food Intake of 20 g/day and mean body weight of 0.4 kg) (BMeger, 1953b). 6.1.3. Other Relevant Information. A suicide occurred with acute 1ngest1on of -100 mg endothall 1on/kg (Allender, 1983). Repeated vomiting was consistent with 1ngest1on of an Irritant. The autopsy showed focal edema and focal hemorrhages In the lungs and gross hemorrhage of the gastro- intestinal tract. Male Swiss-Webster mice, weighing 20-25 g (numbers not specified), were Injected IntraperUoneally with a single dose of 75 mg/kg endothall and 10 mg/kg cantharldlc add (Grazlano and Caslda, 1987). (Cantharldlc acid 1s similar In structure to endothall and both compounds cause similar signs of acute toxlclty.) This dose was lethal, usually producing death within 60-90 minutes. Animals that were sacrificed by cervical dislocation after 45 minutes had significantly Increased liver weights (-36%) and hepatic hemo- globin levels (~100%). Hepatic glycogen metabolism Increased, while hepatic ATP concentrations decreased. No changes were seen 1n hepatic GSH content, mlcrosomal I1p1d peroxldatlon, hepatic trlglycerldes or SGPT levels. An oral (gavage) LD,. for adult Sherman rats was reported to be 57 mg/kg for males and 46 mg/kg for females for the add form (Galnes and Under, 1986). In another study with rats, the ID™ for orally admin- istered endothall 1n the add form was 38-51 mg/kg and as the sodium salt 0168d -38- 06/19/89 ------- was 182-197 mg/kg (Slmslman et al., 1976; Worthing and Walker, 1983). The Intraperltoneal L05Q for mice was reported to be 14 mg/kg for the add form (Matsuzawa et al., 1987). An Intravenous Injection of 5 mg/kg d1sodium endothal 1s fatal to dogs and rabbits (Goldstein, 1952; Srensek and Woodard, 1951). 6.2. CARCINOGENICITY 6.2.1. Inhalation. Pertinent data regarding the cardnogenlclty of Inhaled endothall were not located 1n the available literature dted 1n Appendix A. 6.2.2. Oral. No statistically significant Increase 1n number of tumors was seen In rats fed diets containing 2500 ppm d1 sodium endothall (equiva- lent to endothall 1on at 100 mg/kg/day) for 2 years (Brleger, 1953b); however, this study probably did not use contemporary cancer testing methodology. 6.2.3. Other Relevant Information. Endothall was positive for transformation In BALB/c 3T3 cells (Litton B1onet1cs, 1981). Pertinent data regarding the cardnogenlclty of endothall administered by other routes were not located 1n the available literature dted 1n Appendix A. 6.3. MUTAGENICITY Endothall was not mutagenlc 1n S. typhlmuMum with or without metabolic activation (Table 6-1) (Andersen et al., 1972; Remondelll et al., 1986; Microbiological Associates, 1980b), In Neurospora crassa (Sandier and Hamllton-Byrd, 1981), and for sister chromatld exchange 1n human lymphocytes (Vlgfusson, 1981). Mixed results were obtained 1n Drosophlla melanogaster (WHson et al., 1956; Sandier and Ham1Hon-Byrd, 1981). 6.4. TERATOGENICITY Pregnant rats (25-26 group) were given oral doses of 0, 10, 20 or 30 mg/kg/day of aqueous endothall technical (0, 8, 16 or 24 mg endothall 0168d -39- 06/19/89 ------- 1ABIF 6-1 Mulagenlclty and Genotoxlcily Summary lable for Endothall 00 o. Assay Reverse mutation Reverse mutation Reverse mutation forward mutation Mutagcnlcity assay i g Sister chromatld i exchange Point mutation Sex-linked recessive lethal Sex-linked recessive lethal Indicator/Organism Salmonella typhlmurlum 8 mutants S. typhlmurluro S. typhlmurlum TA98. TA100. TA1537. TA9?. 1A2637 S. typhlmurluro 1A98, 1A100 Neurospora crassa human lymphocytes BALB/313 clone A31 mouse cells Orosophila melanoqaster D. melanogaster Purity technical technical technical technical ?8.6X acid equivalent 28. 6X acid equivalent technical "commercial" 28.6% acid equivalent Application plate NR plate Incorpora- tion tube Incubation NR cell culture cell culture vapor exposure of adults and larval feeding NR Concentration/Dose 1-5 pi NR <5.0 ing/plate NR NR NR NR vapor. NR/feeding. 100 and 250 ppm NR Activating Response System »S9 - ,S9 - 1 fS9 - 1 - »S9 - 1 - NR - ' 1 NR none - 1 i NA * (both vapor 1 and larval) NA 1 Reference Andersen el al., 197? Microbiological Associates, 1980a RemondelII et al., 1986 Remondel11 et al.. 1986 Sandier and Hamilton-Byrd, 1981 Vigfusson. 1981 Microbiological Associates, 1980b Wilson et al.. 1956 Sandier and Hamllton-Byrd, 1981 *It was unclear whether positive result occurred both with and without metabolic activation. NR = Not reported; NA = not applicable CD CD ------- 1on/kg/day) on gestation days 6-19 (Science Applications, Inc., 1982). Maternal deaths occurred at the two higher doses, but the fetuses of the surviving dams exhibited no signs of teratogenldty or fetotoxldty. No effects were observed on the dams or fetuses at the low dose. A NOAEL of 10 mg endothall technlcal/kg/day (8 mg/kg/day of endothall 1on) was Identified from this study for teratogenlc effects based on maternal effects. 6.5. OTHER REPRODUCTIVE EFFECTS Hale and female rats were fed diets containing dlsodlum endothall at 0, 100, 300 or 2500 ppm (equivalent to 0. 4, 12 or 100 mg/kg/day of endothall 1on) until they were 100 days old (Scientific Associates, 1965). They were mated and the offspring were maintained on the same diet, again for 100 days, when they were mated. The third generation was treated similarly. At the low dose, there was no effect; at the middle dose level, the pups had reduced body weights at 21 days of age. At the high dose, the pups died within 1 week of birth and this dosage was discontinued. A NOAEL for reproductive effects of 4 mg 1on/kg/day was Identified. 6.6. SUMMARY Minimal data were located In the available literature regarding the health effects of endothall. Acute toxlclty appears to be substantially greater for the add form than for the dlsodlum salt. Oral LD5Q values for rats of 38-57 mg/kg have been reported for the add form (Worthing and Walker, 1983; Galnes and Under, 1986) and 182-197 mg/kg have been reported for the dlsodlum salt. Acute exposure to large doses Is extremely Irritat- ing and causes erosion and hemorrhage of the stomach (Allender, 1983; Brleger, 1953b). Subchronlc data suggest that dogs may be more sensitive than rats to oral exposure to endothall. In a dietary study, rats succumbed to dosages 0168d -41- 06/19/89 ------- of the Ion of 400 mg/kg/day and exhibited liver and kidney lesions at 40 mg/kg/day (Brleger, 1953a). Dogs treated by capsule, however, died at 20 mg/kg/day d1sodium endothall (16 mg/kg/day endothall Ion) and had congestion and edema of the stomach at 0.8 mg/kg/day of endothall Ion (Brleger, 1953b). The Investigators suggested that the lesions 1n the stomach resulted from the administration of the undiluted test solution without food. There are notable discrepancies between the subchronlc and chronic data. For example, no toxic effects were reported 1n a 2-year dietary study where rats were exposed to 2500 ppm dlsodlum endothall (100 mg/kg bw/day of endo- thall Ion) (Brleger, 1953b). In a 2-year dietary study using dogs (4/dose), elevated relative and absolute stomach and small Intestine weights were Increased with dlsodlum endothall at 300 and 800 ppm (6 and 16 mg/kg/day of endothall 1on), but no effects were observed at 100 ppm (2 mg/kg/day of the 1on) (Keller, 1965; Penwalt Agchem, n.d.). Developmental toxlclty studies using rats suggest that the dams are more susceptible than the fetuses to oral administration of endothall (Science Applications, Inc., 1982). In a dietary study, pregnant rats were given 0, 8, 16 or 24 mg endothall 1 on/kg/day on gestation days 6-19. Maternal deaths occurred at the two higher doses but the fetuses of the surviving dams exhibited no signs of teratogenlclty or fetotoxldty. A NOAEL of 8 mg/kg/day was Identified from this study for teratogenlclty based on maternal effects. In a 3-generatlon reproductive study, no effects were observed when rats were exposed to dlsodlum endothall 1n the diet that provided a dosage of endothall 1on at 4 mg/kg/day (Scientific Associates, 1965). In the same 3-generat1on study, however, pups In the 12 mg/kg/day group had reduced body weights and pups In 100 mg/kg/day group died within a week of birth. 0168d -42- 06/19/89 ------- Endothall has not been adequately tested for carclnogenldty. There was no evidence of cardnogenlcHy In rats fed diets containing dlsodlum endo- thall at <2500 ppm (100 mg/kg/day of the 1on) for 2 years 1n an early study (Brleger, 1953b). Endothall Induced malignant transformation of BALB/c 3T3 cells (Utton B1onet1cs, Inc., 1981). Endothall was not mutagenk 1n microorganisms (Andersen et al., 1972; RemondelH et al., 1986; Microbiological Associates, 1980a; Sandier and Ham1lton-Byrd, 1981) and In human lymphocytes (Vlgfusson, 1981). Mixed results were obtained 1n Drosophla (Wilson et al., 1956; Sandier and Ham1lton-Byrd, 1981). 0168d -43- 06/19/89 ------- 7. EXISTING GUIDELINES 7.1. HUMAN The verified IRIS oral RfD 1s 0.02 mg/kg/day (U.S. EPA, 1986d), based on a NOEL for gastrointestinal effects In dogs In a 2-year feeding study (Pennwalt Agchem, n.d.; Keller, 1965). U.S. EPA (1987a) derived a Lifetime Health Advisory of 0.14 mg/l based on the ADI set by U.S. EPA Office of Pesticide Programs of 0.02 mg/kg/day. The 1- and 10-day HAs for a 10 kg child are 0.8 mg/l based on a NOAEL of 8 mg/kg/day for the absence of fetal and maternal effects 1n rats exposed to endothall acid orally for 13 days (Science Applications, 1982). The DUEL 1s 0.7 mg/l based on the 2-year study using dogs (Keller, 1965). Endothall 1s Included In a 11st of 83 chemicals required to be regulated by the Agency under a 1986 amendment of the Safe Drinking Water Act (U.S. EPA, 1987b). An Interim tolerance of 0.2 ppm has been established for Its residues 1n potable water resulting from use of endothall salts to control aquatic plants (U.S. EPA, 1987c). Tolerances In raw agricultural commodities are 0.1 ppm 1n cottonseed and potatoes and 0.05 ppm 1n rice grain and rice straw (U.S. EPA, 1982). The RQ 1s 1000 (U. S. EPA, 1985). 7.2. AQUATIC Guidelines and standards for the protection of aquatic life from exposure to endothall were not located In the available literature cited In Appendix A. 0168d -44- 06/19/89 ------- 8. RISK ASSESSMENT Statements concerning available literature 1n this document refer to published, quotable sources and are 1n no way meant to Imply that confiden- tial business Information (CBI), which this document could not address, do not exist. From examination of the bibliographies of the CBI data, however, 1t was determined that CBI data that would alter the approach to risk assessment or the risk assessment values presented herein do not exist. 8.1. CARCINOGENICITY 8.1.1. Inhalation. No data were available to assess the carcinogenic potential of endothall by the Inhalation route. 8.1.2. Oral. Rats fed <100 mg 1on/kg/day for 2 years had no significant Increase 1n number of tumors (Brleger, 1953b). 8.1.3. Other Routes. No data were available to assess the carcinogenic potential of endothall from other routes. 8.1.4. Weight of Evidence. No data were available regarding the carclno- genldty of endothall In humans. Rats fed <100 mg lon/kg/day for 2 years had no significant Increase In number of tumors (Brleger, 1953b), but the adequacy of this study as a cancer bloassay cannot be evaluated because of the lack of the primary report. Also, H 1s likely that this early study did not use contemporary cancer testing methodology. The animal data are Insufficient. Therefore, endothall Is assigned to EPA Group D, not classi- fiable as to human cardnogenlclty (U.S. EPA, 1986a). This 1s consistent with the classification assigned by the Agency 1n an earlier evaluation (U.S. EPA, 1987a). 8.1.5. Quantitative Risk Estimates. No q^* can be derived because endothall 1s assigned to EPA Group D. 0168d -45- 04/19/89 ------- 8,2. SYSTEMIC TOXICITY 8.2.1. Inhalation Exposure. No data were available to assess the systemic toxldty of endothall from Inhalation. 8.2.2. Oral Exposure. 8.2.2.1. LESS THAN LIFETIME EXPOSURE (SUBCHRONIC) — Subchronlc oral data consist of a 4-week study using rats and a 6-week study using dogs. These studies were available only as very brief reviews by U.S. EPA (1987a) of the Confidential Business Information (CBI) studies from the Office of Pesticides Program files. In the rat study, dietary dlsodlum endothall provided dosages of endothall 1on of 40 or 400 mg/kg/day (BHeger, 1953a). Most rats at 400 mg/kg/day died within 1 week; liver degeneration and hemor- rhaglc areas 1n the kidneys were reported at 40 mg/kg/day. Dogs treated with dlsodlum endothall 1n capsules died and had erosions and hemorrhage 1n the stomach at doses >20 mg/kg/day (16 mg/kg/day of the 1on) (Brleger, 1953b). Stomach lesions were observed at 1 mg/kg/day dlsodlum endothall, the lowest dose tested. The Investigators suggested that the lesions 1n the stomachs of dogs at very low dosages resulted from the administration of the undiluted test material without food (U.S. EPA, 19866). These data suggest that dogs are more sensitive than rats to endothall, but are Insufficient for derivation of an RfD for subchronlc oral exposure. The chronic oral RfD of 0.02 mg/kg/day (Section 8.2.2.2.) 1s adopted as the subchronlc oral RfD. Confidence In the key study Is medium (U.S. EPA, 1986d), which 1s apparently due 1n part to the limited number of animals per dose and the limited range of doses. Confidence 1n the data base and RfD also are medium (U.S. EPA, 1986d). 0168d -46- 06/19/89 ------- 8.2.2.2. CHRONIC EXPOSURES — Chronic data for endothall are limited to two 2-year CBI studies using rats and dogs. Brleger (1953b) reported no effects In rats fed a diet containing dlsodlum endothall at 2500 ppm (100 mg/kg bw/day of endothall 1on). In dogs fed dlsodlum endothall 1n the diet at 0, 100, 300 or 800 ppm (dosages of endothall 1on of 0, 2, 6 or 16 mg/kg/day), elevated stomach weights were observed at >300 ppm, but no effects were observed at 100 ppm (2 mg/kg/day) (Keller, 1965; Pennwalt Agchem, n.d.). U.S. EPA (1986d, 1987a) derived an RfD for endothall of 0.02 mg/kg/day by applying an uncertainty factor of 100 (10 for Interspedes differences, 10 for Intraspedes differences) to the dog NOEL of 2 mg/kg/ day. Stomach lesions were observed 1n dogs treated with 0.8 mg endothall lon/kg/day by capsule for 6 weeks (Brleger, 1953b). Although lower than the 2 mg/kg day NOEL, this LOAEL Is an Inappropriate basis for an RfD because of the bolus method of treatment (capsule without food), which does not repre- sent environmental exposure. However, unprotected endothall applicators or members of the general population near application sites could swallow low doses of endothall following dust exposure (I.e., by mucodllary clearance). The RfD of 0.02 mg/kg/day, which Is verified and available on IRIS (U.S. EPA, 1986d), therefore, Is adopted as the RfD for chronic exposure to endothall for the purposes of this document. Confidence 1n the key study, data base and RfD are medium (U.S. EPA, 1986d). 0168d -47- 06/19/89 ------- 9. REPORTABLE QUANTITIES 9.1. BASED ON SYSTEMIC TOXICITY The systemic toxldty of endothall was discussed In Chapter 6. Data from these studies relevant for derivation of CSs are summarized In Table 9-1. In the 24-month study using dogs, slight edema and Increased mucosal gland activity were observed at a dosage of 16 mg/kg/day endothall 1on; Increased absolute and relative weights of the stomach and small Intestine were reported at 6 mg/kg/day (Keller, 1965; Pennwalt Agchem, n.d.). Conges- tion and edema of the stomach and edema of the upper Intestines at 1 mg dlsodlum endothall/kg/day and death at 20 mg/kg/day reported In a 6-week dog study by BMeger (1953b) 1s not Included In Table 9-1 because undiluted compound had been administered In capsules not accompanied by food, a protocol not relevant to environmental exposure. Death observed In rats at 10,000 ppm dlsodlum endothall 1n the diet and the liver and kidney lesions at 1000 ppm In the diet In the 4-week rat study by BMeger (1953a) are not Included because the study duration was too short. Composite scores for the effects presented 1n Table 9-1 are calculated 1n Table 9-2. The CS of 7.6 for Increased relative and absolute weight of stomach and small Intestine In dogs (Keller, 1965; Pennwalt Agchem, n.d.}, equivalent to an RQ of 1000, Is chosen to represent the chronic toxldty of endothall (Table 9-3). 9.2. BASED ON CARCINOGENICITY Cancer data for endothall (see Section 6.2.) consist of the statement that rats fed diets containing 2500 ppm dlsodlum endothall for 2 years (100 mg endothall 1on/kg/clay) had no significant Increase In tumor Incidence, but the adequacy of this study cannot be evaluated. Endothall Is assigned to EPA Group D. Because hazard ranking 1s not possible for Group D compounds, a cancer-based RQ cannot be assigned to endothall. 0168d -48- 04/19/89 ------- cr oo TABLE 9-1 Toxlclty Summary for Oral Exposure to Endothall Using the Beagle Doga»b No. /Sex Exposure Transformed Animal Dosec (mg/kg/day) Equivalent Human Dosed (mg/kg/day) Response 4/sex 4/sex 800 ppm dlsodium endothall In diet for 24 months 300 ppm dlsodium endothall In diet for 24 months 16 9.1 3.4 Slight edema and In- creased mucosal gland activity In stomach Increased absolute and relative weights of stomach and small Intestine aSource: Keller, 1965; Pennwalt Agehem, n.d. Reference body weight for dogs = 12.7 kg (U.S. EPA, 1986c) Expressed as endothall Ion dThe transformed animal dose Is multiplied by the cube root of the ratio of the animal body weight to reference human body weight (70 kg). o -f* CO to ------- TABLE 9-2 Composite Scores for Endothall Ion Using the Doga Animal Dose (mg/kg/day) Chronic Human MEOb (mg/day) RVd Effect RVe CS RQ 16 637 1.3 Slight edema and In- creased mucosal gland activity In stomach 238 1.9 Increased absolute and relative weight of stomach and small Intestine 5 6.5 1000 4 7.6 1000 aSource: Keller, 1965; Pennwalt Agchem, n.d. Equivalent human dose multiplied by 7,0 kg to express MED as mg/day for a 70 kg human 0168d -50- 04/19/89 ------- TABLE 9-3 ENOOTHALL Minimum Effective Dose (MED) and Reportable Quantity (RQ) Route: Dose*: Effect: RVd: RVe: Composite Score: RQ: Reference: oral 238 tug/day Increased stomach and small Intestine weights 1.9 4 7.6 1000 Keller 1965; Pennwalt Agchem, n.d. *Equ1valent human dose 0168d -51- 04/19/89 ------- 10. REFERENCES Allender, W.J. 1983. Suicidal poisoning by endothall. J. Anal. Toxlcol. 7(2): 79-82. Andersen, K.J., E.G. Lelghty and M.T. Takahashl. 1972. Evaluation of herbicides for possible mutagenlc properties. J. Agrlc. Food Chem. 20: 649-654. Beckmann, J., P. Tazlk and R. Gorden. 1984. Effects of two herbicides on selected aquatic bacteria. Bull. Environ. Contam. Toxlcol. 32(2): 243-250. Berry, C.R., Jr. 1984. Toxlclty of the herbicides dlquat and endothall to goldfish (Carasslus auratus). Environ. Pollut. Ser. A. Ecol. B1ol. 34(3): 251-258. Brleger, H. 1953a. Preliminary studies on the toxlclty of endothall (dlsodlum). EPA Pesticide Petition No. 6G0503, redeslgnated No. 7F0570, 1966. Accession No. 246012. (Cited In U.S. EPA, 1987a) Brleger, H. 1953b. Endothall, long term oral toxlclty test—rats. EPA Pesticide Petition No. 6G0503, redeslgnated No. 7F0570, 1966. Accession No. 246012. (Cited 1n U.S. EPA, 1987a) Cain, J.R. and R.K. Cain. 1983. The effects of selected herbicides on zygospore germination and growth of Chlamydomonas moewusll (Chlorophyceae, volvocales). J. Phycol. 19(3): 301-305. 0168d -52- 04/19/89 ------- Crockett, P.W., B. Klllan, K.S. Crump and R.B. Howe. 1985. Descriptive Methods for Using Data from Dissimilar Experiments to Locate a No-Adverse- Toxic-Effects Region 1n the Dose-Duration Plane. Prepared by K.S. Crump and Company, Inc., under Contract No. 68-01-6807 for Environmental Criteria and Assessment Office, Cincinnati, OH. Crosby, D.G. and R.K. Tucker. 1966. Toxlclty of aquatic herbicides to Daphnla magna. Science. 154: 289-291. Durkln, P. and W. Meylan. 1988. Users Guide for D2PLOT: A Program for Dose/Duration Graphs. Prepared by Chemical Hazard Assessment Division, Syracuse Research Corporation, under Contract No. 68-C8-0004 for Environ- mental Criteria and Assessment Office, Cincinnati, OH. E1senre1ch, S.J., B.B. Looney and J.D. Thornton. 1981. Airborne organic contaminants of the Great Lakes ecosystem. Environ. Scl. Technol. 15(1): 30-38. Flnlayson, B.J. 1980. Acute toxldtles of the herbicide Komeen and Hydro- thol-191 to golden shiner. Bull. Environ. Contam. Toxlcol. 25(4): 676-681. Folmar, L.C. 1976. Overt avoidance reaction of rainbow trout fry to nine herbicides. Bull. Environ. Contam. Toxlcol. 15(5): 509-514. Folmar, L.C. 1977. Acroleln, dalapon, dlchlobenll, dlquat and endothall: Bibliography of toxldty of aquatic organisms. Tech. Pap. U.S. Fish W1ldl. Serv. 88: 16 p. 0168d -53- 04/19/89 ------- Folmar, L.C. 1978. Avoidance chamber responses of mayfly nymphs exposed to eight herbicides. Bull. Environ. Contam. Toxlcol. 19(3): 312-318. Galnes, T.B. and R.E. Under. 1986. Acute toxlclty of pesticides In adult and weanling rats. Fund. Appl. Toxlcol. 7: 299-308. Goldstein, F. 1952. Cutaneous and Intravenous toxlclty of endothalls (d1sod1um-3-endohexahydrophthal1c add). Pharmacol. Exp. Ther. 11: 349. (CHed 1n U.S. EPA, 1987a) Grazlano, M.J. and J.E. Caslda. 1987. Comparison of the acute toxlclty of endothal and canthaMdlc add on mouse liver In vivo. Toxlcol. Lett. 37(2): 143-148. Hansen, C.R., Jr. and J.A. Kawatskl. 1976. Application of 24-hour post- exposure observation to acute toxlclty studies with Invertegrates. J. Fish. Res. Bd. Can. 33(5): 1198-1201. Hartley, D. and H. K1dd. 1983. The Agrochemlcals Handbook. Royal Society of Chemistry, Nottingham, England. H1ne, J. and P.K. Mookerjee. 1975. The Intrinsic hydrophHU character of organic compounds. Correlations 1n terms of structural contributions. J. Org. Chem. 40(3): 292-298. Holmberg, D.J. and G.F. Lee. 1976. Effects and persistence of endothall In the aquatic environment. J. Water Pollut. Control Fed. 48: 2738-2746. 0168d -54- 04/19/89 ------- HSDB (Hazardous Substance Data Base). 1988. Record #391. On-line 5-17-88. Hughes, J.S. and J.T. Davis. 1965. Comparative ToxIcHy to Blueglll Sun- fish of Granular and Liquid Herbicides. Proc. 15th. Ann. Conf., Southeast Assoc. Game F1sh Comm. p. 319-323. Inglls, A. and E.L. Davis. 1973. Effects of water hardness on the toxlclty of several organic and Inorganic herbicides to fish. U.S. Bur. Sport F1sh Wlldl. Tech. Pap. 67: 1-22. Isensee, A.R. 1976. Variability of aquatic model ecosystem-derived data. Int. J. Environ. Stud. 10(1): 35-41. Keller, J. 1965. Two-year chronic feeding study of dlsodlum endothall to beagle dogs. Scientific Associates report. EPA Pesticide Petition 6G0503, redeslgnated No. 7F0570, June 1966. Accession No. 24601. (Cited 1n U.S. EPA, 1987a) Langeland, K.A. and J.P. Warner. 1986. Persistence of dlquat, endothall and flurldone In ponds. J. Aquat. Plant Manage. 24: 43-46. LlguoM, V.M., H.R. Zakour, M.L. Landolt and S.P. Felton. 1983. ToxIcHy of the herbicide endothall to Juvenile Chinook salmon (Oncorhynchus tshawytscha). ISS Aquat. Toxlcol. Hazard Assess. 802: 530-544. 0168d -55- 04/19/89 ------- Litton Blonetlcs, Inc. 1981. Evaluation of Aquathol K 1n the \n_ vitro transformation of BALB/3T3 cells with and without metabolic activation assay. Project No. 20992. Report to Municipality of Metropolitan Seattle, Seattle, WA, by Litton Blonetlcs, Inc., Rockvllle, MD. (Cited 1n U.S. EPA, 1987a) Mantel, N. and M.A. Schnelderman. 1975. Estimating "safe" levels, a hazardous undertaking. Cancer Res. 35: 1379-1386. Martin, H. and C.R. Worthing, Ed. 1979. The Pesticide Manual, 5th ed. British Crop Protection Council, p. 233. Matsuzawa, M., M.J. Grazlano and J.E. Caslda. 1987. Endothall and cantharldln analogues: Relation of structure to herblddal activity and mammalian toxlclty. J. Agrlc. Food Chem. 35(5): 823-829. Mayer, F.L., Jr. and M.R. Ellersleck. 1986. Manual of Acute Toxldty: Interpretation and Data Base for 410 Chemicals and 55 Species of Freshwater Animals. U.S. Dept. Int. F1sh and Wildlife Service. Resource Publ. 160, Washington, DC. Melster, R.T., Ed. 1988. Farm Chemicals Handbook '88. Melster Publishing Co., Wllloughby, OH. p. C-92. Microbiological Associates. 1980a. Activity of T1604 In the Salmonella/ mlcrosomal assay for bacterial mutagenldty. Unpublished final report for Pennwalt Corp., by Microbiological Associates, Bethesda, MD. (Cited In U.S. EPA, 1987a) 0168d -56- 04/19/89 ------- M1crob1olog1al Associates. 1980b. Activity of T1604 1n the Ui vitro mammalian cell point mutation assay In the absence of exogenous metabolic activation. Unpublished final report for Pennwalt Corp., by Microbiological Associates, Bethesda, MO. (Cited 1n U.S. EPA, 1987a) Nebeker, A.V. and A.R. Gaufln. 1964. Bloassays to determine pesticide toxldty to the amphlpod crustacean, Gammarus lacustrls. Proc. Utah Acad. Sc1. 41(1): 64-67. Pennwalt Agchem. n.d. MRIO No. 00101735. Available from U.S. EPA. Write to FOI, EPA, Washington, DC 20460. (Cited 1n U.S. EPA, 1988} Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target Species. Presidential Report, Office of Science and Technology, p. 89-136. Relnert, K.H. and J.H. Rodgers, Jr. 1984. Influence of sediment types of the sorptlon of endothall. Bull. Environ. Contam. Toxlcol. 32: 557-564. Relnert, K.H. and J.H. Rodgers. 1986. Validation trial of predictive fate models using an aquatic herbicide (endothall). Environ. Toxlcol. Chem. 5(5): 449-461. Relnert, K.H. and J.H. Rodgers. 1987. Fate and persistence of aquatic herbicides. Rev. Environ. Contam. Toxlcol. 98: 61-91. Relnert, K.H., J.H. Rodgers, Jr., M.L. Hlnman and T.J. Leslie. 1985. Compartmental1zat1on and persistence of endothall 1n experimental pools. Ecotoxlcol. Environ. Saf. 10(1): 86-96. 0168d -57- 04/19/89 ------- Relnert, K.H., G.H. Rodgers, Jr., T.J. Leslie and M.L. Hlnman. 1986. Static shake-flask blotransformatlon of endothall. Mater Res. p. 255-258. Relnert, K.H., M.L. Hlnman and J.H. Rodgers, Jr. 1988. Fate of endothall during the pat Mayse Lake (Texas) aquatic plant management program. Arch. Environ. Contam. Toxlcol. 17: 195-199. RemondelH, P., B. Mugnoz, R. Delia Morte, M.A. Bellsarlo, N. Stalano and F. De Lorenzo. 1986. Evaluation of the mutagenlc potential of thirteen pesticides by measuring both h1s+ and HGPRT-deflclent mutants In Salmonella typhlmurlum. Med. B1ol. Environ. 14(1): 377-386. Sandier, L. and E.L. Ham1lton-Byrd. 1981. The Induction of sex-linked recessive ethal mutations 1n Drosophlla melanogaster by Aquathol K, as measured by the Huller-5 test. Report to Municipality of Metropolitan Seattle, Seattle, WA. (Cited 1n U.S. EPA, 1987a) SANSS (Structure and Nomenclature Search System). 1987. Chemical Informa- tion System (CIS) computer data base. On-line. May 13, 1988. Science Applications, Inc. 1982. A dose range-finding teratology study of endothall technical and dlsodlum endothall In albino rats. Resubmlsslon of Pesticide Application for Aquathol K Aquatic Herbicide (EPA Registration No. 4581-204) and Hydrothal 191 Aquatic Alglclde and Herbicide (EPA Registration No. 4581-174). EPA Accession No. 071249. (Cited 1n U.S. EPA, 1987a) 0168d -58- 04/19/89 ------- Scientific Associates. 1965. Three generation rat reproductive study, d1 sodium endothall. EPA Pesticide Petition No. 6G0503, redeslgnated 7F0570, 1966. EPA Accession No. 114667. (Cited 1n U.S. EPA, 1987a) Serns, S.L. 1975. The effects of dlpotasslum endothall on the zooplankton and water quality of a small pond. 1975. Mater Resour. Bull. 11(6): 1221-1231. Serns, S.L. 1977. Effect of dlpotasslum endothall on rooted aquatics and adult and first generation bluegllls. Water Resour. Bull. 13(1): 71-80. S1kka, H.C. and C.P. R1ce. 1973. Persistence of endothall 1n aquatic environment as determined by gas-liquid chromatography. Agrlc. Food Chem. 21: 842-846. S1kka, H.C. and J. Saxena. 1973. Metabolism of endothall by aquatic micro- organisms. J. Agrlc. Food Chem. 21: 402-406. S1kka. H.C., D. Ford and R.S. Lynch. 1975. Uptake, distribution and metabolism of endothall 1n fish. 3. Agrlc. Food Chem. 23(5): 849-851. S1ms1man, G.V. and 6. Chesters. 1975. Persistence of endothall In the aquatic environment. Water A1r Soil Pollut. 4: 399-413. Slmslman, G.V., T.C. Daniel and 6. Chesters. 1976. Dlquat and endothall: Their fates 1n the environment. Res. Rev. 62: 131-174. 0168d -59- 04/19/89 ------- Soo, A., I. "Mnsley and S.C. Fang. 1967. Metabolism of 14C-endothall 1n rats. J. Agrlc. Food Chem. 15(6): 1018-1021. Srensek, S.E. and G. Woodard. 1951. Pharmacological actions of "endothall" (d1sod1um-3,6-endoxo-hexahydrophtha!1c add). Fed. Proc. 10: 337. (Abstract) SRI (Stanford Research Institute). 1987. 1987 Directory of Chemical Producers: United States of America. SRI International, Menlo Park, CA. p. 847. Swann, R.L., D.A. Laskowskl, P.O. McCall, K. Vander Kuy and H.J. Dlshburger. 1983. A Rapid Method for the Estimation of the Environmental Parameters Octanol/Water Partition Coefficient, Soil Sorptlon Constant, Water to Air Ratio and Water Solubility. Res. Rev. 85: 17-28. Tweedy, B.G. and L.O. Houseworth. 1976. Miscellaneous herbicides. Irr. Herbicides: Chemistry, Degradation and Mode of Action, Vol. 2, 2nd ed., P.C. Kearney and D.D. Kaufman, Ed. Marcel Dekker, Inc., New York, NY. p. 815-833. U.S. EPA. 1980. Guidelines and Methodology Used In the Preparation of Health Effect Assessment Chapters of the Consent Decree Water Criteria Documents. Federal Register. 45(231): 79347-79357. U.S. EPA. 1982. Endothall; tolerance for residues. Code of Federal Regulations. 40 CFR 180.293. 0168d -60- 04/19/89 ------- U.S. EPA. 1984. Methodology and Guidelines for Ranking Chemicals Based on Chronic Toxldty Data. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC. U.S. EPA. 1985. Reportable Quantity Adjustments. 40 CFR parts 117 and 302. Federal Register. Vol. 50 No. 65, April 4, 1985. U.S. EPA. 1986a. Guidelines for Carcinogen Risk Assessment. Federal Register. 51(185): 33992-34003. U.S. EPA. 19865. CBI Appendix for Review and Evaluation of ADI for P088 Endothall. Prepared Under Contract No. 68-03-3228 for Environmental Criteria and Assessment Office, Cincinnati, OH. U.S. EPA. 1986c. Reference Values for Risk Assessment. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste, Washington, DC. U.S. EPA. 1986d. Integrated Risk Information System (IRIS): Reference Dose (RfD) for oral exposure for Endothall. Online. (Revised; Verification date 11/25/86.) Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH. U.S. EPA. 1987a. Health Advisories for 50 Pesticides. Endothall (draft). Office of Drinking Water, Washington DC. NTIS PB88-113543. 0168d -61- 07/14/89 ------- U.S. EPA. 1987b. Drinking Water, Proposed Substitution of Contaminants and Proposed List of Additional Substances Which Hay Require Regulation Under the Safe Drinking Water Act. Federal Register. 40 CFR part 141. U.S. EPA. 1987c. Pesticide Residues. Code of Federal Regulations. 21 CFR 193.180. U.S. EPA/OWRS (Office of Water Regulations and Standards). 1985. Guide- lines for Deriving Numerical National Water Quality Criteria for the Protec- tion of Aquatic Organisms and Their Uses. U.S. EPA, Washington, DC. 106 p. USITC (U.S. International Trade Commission). 1987. 1986 Synthetic Organic Chemicals United States Production and Sales. USITC Publ. 2009, Washington, DC. p. 185, 190. Vlgfusson, N.V. 1981. Evaluation of the mutagenlc potential of Aquathol K by Induction of sister chromatld exchanges 1n human lymphocytes jm vitro. Report to Municipality of Metropolitan Seattle, Seattle, WA. (Cited In U.S. EPA, 1987a) Walsh, G.E. 1972. Effects of herbicides on photosynthesis and growth of marine unicellular algae. Hyacinth Control J. 0: 45-48. Wellborn, J. 1971. Tox1c1ty of some compounds to striped bass flngerllngs. Prog. Fish-Cult. 33(1): 32-36. 0168d -62- 07/14/89 ------- Ullllams, E.H., E.L. Mather and S.M. Carter. 1984. Toxlclty of the herbi- cides endothall and dlquat to benthlc Crustacea. Bull. Environ. Contain. Toxlcol. 33(4): 418-422. Wilson, S.M., A. Daniel and G.B. Wilson. 1956. Cytologlcal and genetic effects of the defoliant endothall. J. Hered. 47: 151-154. Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual, 7th ed. British Crop Protection Council, p. 234. WSSA (Weed Science Society of America). 1983. Herbicide Handbook, 5th ed. WSSA, Champaign, IL. p. 208-210. Yeo, R.R. 1970. Dissipation of endothall and effects on aquatic weeds and fish. Weed Sd. 18(2): 282-284. 0168d -63- 04/19/89 ------- APPENDIX A LITERATURE SEARCHED This HEED Is based on data Identified by computerized literature searches of the following: CHEMLINE TSCATS CASR online (U.S. EPA Chemical Activities Status Report) TOXLINE TOXLIT TOXLIT 65 RTECS OHM TADS STORET SRC Environmental Fate Data Bases SANSS AQUIRE TSCAPP NTIS Federal Register CAS ONLINE (Chemistry and Aquatic) HSDB SCISEARCH Federal Research In Progress These searches were conducted In Hay, 1988, and the following secondary sources were reviewed: ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1986. Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th ed. Cincinnati, OH. ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1987. TLVs: Threshold Limit Values for Chemical Substances 1n the Work Environment adopted by ACGIH with Intended Changes for 1987-1988. Cincinnati, OH. 114 p. Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 2A. John Wiley and Sons, NY. 2878 p. Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 2B. John Wiley and Sons, NY. p. 2879-3816. 0168d -64- 04/19/89 ------- Clayton, G.D. and F.E. Clayton, Ed. 1982. Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John Wiley and Sons, NY. p. 3817-5112. Grayson, M. and D. Eckroth, Ed. 1978-1984. Klrk-Othmer Encyclo- pedia of Chemical Technology, 3rd ed. John Wiley and Sons, NY. 23 Volumes. Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed. Publishing Sciences Group, Inc., Littleton, MA. 575 p. IARC (International Agency for Research on Cancer). IARC Mono- graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humans. IARC, WHO, Lyons, France. Jaber, H.M., W.R. Mabey, A.T. Lieu, T.W. Chou and H.L. Johnson. 1984. Data acquisition for environmental transport and fate screening for compounds of Interest to the Office of Solid Waste. EPA 600/6-84-010. NTIS PB84-243906. SRI International, Menlo Park, CA. NTP (National Toxicology Program). 1987. Toxicology Research and Testing Program. Chemicals on Standard Protocol. Management Status. Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide Register. McGraw-Hill Book Co., NY. Sax, I.N. 1984. Dangerous Properties of Industrial Materials, 6th ed. Van Nostrand Relnhold Co., NY. SRI (Stanford Research Institute). 1987. Directory of Chemical Producers. Menlo Park, CA. U.S. EPA. 1986. Report on Status Report In the Special Review Program, Registration Standards Program and the Data Call 1n Programs. Registration Standards and the Data Call 1n Programs. Office of Pesticide Programs, Washington, DC. USITC (U.S. International Trade Commission). 1986. Synthetic Organic Chemicals. U.S. Production and Sales, 1985, USITC Publ. 1892, Washington, DC. Verschueren, K. 1983. Handbook of Environmental Data on Organic Chemicals, 2nd ed. Van Nostrand Relnhold Co., NY. Wlndholz, M., Ed. 1983. The Merck Index, 10th ed. Merck and Co., Inc., Rahway, NJ. Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual. British Crop Protection Council. 695 p. 0168d -65- 04/19/89 ------- In addition, approximately 30 compendia of aquatic toxldty data were reviewed, Including the following: Battelle's Columbus Laboratories. 1971. Mater Quality Criteria Data Book. Volume 3. Effects of Chemicals on Aquatic Life. Selected Data from the Literature through 1968. Prepared for the U.S. EPA under Contract No. 68-01-0007. Washington, DC. Johnson, W.W. and M.T. Flnley. 1980. Handbook of Acute ToxUHy of Chemicals to Fish and Aquatic Invertebrates. Summaries of Toxldty Tests Conducted at Columbia National Fisheries Research Laboratory. 1965-1978. U.S. Dept. Interior, Fish and Wildlife Serv. Res. Publ. 137, Washington, DC. HcKee, J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed. Prepared for the Resources Agency of California, State Water Quality Control Board. Publ. No. 3-A. Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target Species. Prepared for the U.S. EPA, Washington, DC. PB-269605. Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S. EPA, Washington, DC. EPA 540/9-79-003. NTIS PB 80-196876. 0168d -66- 04/19/89 ------- APPENDIX B Summary Table for Endothall er co O. Species Inhalation Exposure Subchronlc ID Chronic ID Cardnogenlclty ID Oral Exposure i T' Subchronlc dog Chronic dog Cardnogenlclty ID REPORTABLE QUANTITIES Based on Chronic Toxlclty: o vD a Based on Cardnogenlclty: IO Exposure Effect RfD or q-j* ID ID ID ID ID ID ID ID ID 100 ppm dl sodium endothall NOEL for 0.02 In the diet for 2 years stomach effects mg/kg/day (2 mg endothall 1 on/kg/day) 100 ppm dl sodium endothall NOEL for 0.02 In the diet for 2 years stomach effects mg/kg/day (2 mg endothall lon/kg/day) ID ID ID 1000 ID Reference ID ID ID Keller, 1965; Pennwalt Agchem, n.d. Keller. 1965; Pennwalt Agchem, n.d. ID Keller, 1965; Pennwalt Agchem, n.d. NA ID = Insufficient data; NA = not applicable ------- APPENDIX C DOSE/DURATION RESPONSE GRAPH FOR EXPOSURE TO ENDOTHALL C.I. DISCUSSION A dose/duration-response graph for oral exposure to endothall generated by the method of Crockett et al. (1985) using the computer software by Durkln and Meylan (1988) under contract to ECAO-C1nc1nnat1 1s presented In Figure C-l. Data used to generate this graph are presented 1n Section C.2. In the generation of this figure, all responses are classified as adverse (FEL, AEL or LOAEL) or nonadverse (NOEL or NOAEL) for plotting. For oral exposure the ordlnate expresses dosage as human equivalent dose. The animal dosage 1n mg/kg/day Is multiplied by the cube root of the ratio of the animal:human body weight to adjust for species differences In basal meta- bolic rate (Mantel and Schnelderman, 1975). The result 1s then multiplied by 70 kg, the reference human body weight, to express the human equivalent dose as mg/day for a 70 kg human. The boundary for adverse effects (solid line) Is drawn by Identifying the lowest adverse effect dose or concentration at the shortest duration of exposure at which an adverse effect occurred. From this point an Infinite line Is extended upward parallel to the dose axis. The starting point Is then connected to the lowest adverse effect dose or concentration at the next longer duration of exposure that has an adverse effect dose or concen- tration equal to or lower than the previous one. This process 1s continued to the lowest adverse effect dose or concentration. From this point a line 1s extended to the right, parallel to the duration axis. The region of adverse effects lies above the adverse effects boundary. Using the envelope method, the boundary for no adverse effects (dashed line) 1s drawn by Identifying the highest no adverse effects dose or concen- tration. From this point a line parallel to the duration axis 1s extended 0168d -68- 04/19/89 ------- n 1C E v W tfi C Ci = 9 Z C 10000 1000 • r 10 r^ e.00001 (Oral Exposure) .x. 4- q- 8.0881 8.881 0.01 0.1 HUMAN EQUIU DURATION (fPact ion lifespan) ENVELOP METHOD -M 1 2 Key: F - PEL L - LOAEL N - NOEL Solid line - Adverse Effects Boundary Dashed line - No Adverse Effects Boundary FIGURE C-l Dose/Duration - Response Graph for Oral Exposure to Endothall Envelope Method 0168d -69- 04/19/89 ------- to the dose or concentration axis. The starting point Is then connected to the next lower or equal no adverse effect dose or concentration at a longer duration of exposure. When this process can no longer be continued, a line Is dropped parallel to the dose or concentration axis to the duration axis. The region of no adverse effects lies below the no adverse effects boundary. At both ends of the graph between the adverse effects and no adverse effects / boundaries are regions of ambiguity. The area (1f any) resulting from Intersection of the adverse effects and no adverse effects boundaries 1s defined as the region of contradiction. In the censored data method, all no adverse effect points located 1n the region of contradiction are dropped from consideration and the no adverse effect boundary Is redrawn so that 1t does not Intersect the adverse effects boundary and no region of contradiction Is generated. This method results 1n the most conservative definition of the no adverse effects region. Figure C-l presents the dose/duration-response graph generated by the envelope method. The adverse effects boundary Is defined by a lethal dose In humans (Allender, 1983, Rec. #8), a LD,Q value In rats (Slmslman et al., 1976; Worthing and Walker 1983, Rec. #11), and a LOAEL for gastrointes- tinal effects In dogs administered a capsule providing 0.8 mg/kg/day for 2 years (Brleger, 1953b, Rec. #7). The no adverse effects boundary 1s defined by a NOEL for rats In a 2-year diet study (Brleger, 1953b, Rec. #3). As Indicated In Figure C-l, almost all of the points for this chemical fall within the region of contradiction. This Is attributable to the LOAEL (Rec. #7) and NOEL (Rec. #3) described above, which appear to be- outliers. The LOAEL 1s based on a study of low confidence that used a bolus method of treatment, and the NOEL 1s based on a study of Indeterminate confidence using a species that may not be the most sensitive. The LOAEL was not used 0168d -70- 04/19/89 ------- as the basis for an RfD because the method of treatment was Inappropriate (Section 8.2.2.2.). If the LOAEL Is considered to be an outlier, then the NOEL that serves as the basis for the RfD for subchronlc and chronic oral exposure (Keller, 1965; Pennwalt Agchem, n.d., Rec. #1) will not occur within the region of contradiction. Insufficient data are available (because of the outlying points) to redraw the graph by the censored data ,i method to eliminate the region of contradiction. C.2 DATA USED TO GENERATE DOSE/DURATION-RESPONSE GRAPHS Oral Exposure Chemical Name: CAS Number: Document Title: Document Number: Document Date: Document Type: Endothall 145-73-3 Health and Environmental Effects Document on Endothall SRC-TR-88-172 8-30-88 HEED RECORD #1: Species: Dogs Sex: Both Effect: LOAEL Route: Food Number Exposed: Number Responses: Type of Effect: SHe of Effect: Severity Effect: 8 NR WGTIN COLON 4 Dose: 6.000 Duration Exposure: 24.0 months Duration Observation: 24.0 months Comment: Citation: Administered as d1sodium salt. 2, 6 or 16 mg 1on/kg. Increased stomach and small Intestine weight at 6 and 16, slight pylork edema at 16. No effect on SGOT, BSP clearance, hematol, urlnalysls or other hlsto. Keller, 1965; Pennwalt Agchem, n.d. 0168d -71- 04/19/89 ------- RECORD #2: Comment: Citation: Species: Sex: Effect: Route: Dogs Both NOEL Food Dose: 2.000 Duration Exposure: 24.0 months Duration Observation: 24.0 months Number Exposed: 8 Number Responses: NR Type of Effect: WGTIN Site of Effect: COLON Severity Effect: 4 See previous record. Relative and absolute stomach and7 small Intestine weights were not Increased. Keller, 1965; Pennwalt Agchem, n.d. RECORD #3: Species: Sex: Effect: Route: Rats Female NOEL Food Dose: Duration Duration Exposure: Observation: 100.000 2.0 years 2.0 years Comment: Comment: Citation: Number Exposed: Number Responses: Type of Effect: Site of Effect: Severity Effect: NR Administered as dlsodlum salt. Doses were 100 mg 1 on/kg/day and lower (NOS). No toxic effects noted but endpolnts examined were not specified. Study summarized In ODW Health Advisory. Citation: RECORD #4: Brleger, Species: Sex: Effect: Route: )953b Rats NR FEL Food Dose: Duration Duration Exposure: Observation: 400.000 4.0 weeks 4.0 weeks Number Exposed: NR Number Responses: NR Type of Effect: MORTL Site of Effect: BODY Severity Effect: 10 Administered as dlsodlum salt. Doses were 40 and 400 mg Ion/ kg/day. Most rats died within 1 week. Not specified 1f liver or kidney effects occurred. Study summarized 1n ODW Health Advisory. Brleger, 1953a 0168d -72- 04/19/89 ------- RECORD #5: Comment: Citation: Species: Sex: Effect: Route: Rats NR LOAEL Food Number Exposed: NR Number Responses: NR Type of Effect: OEGEN SHe of Effect: LIVER Severity Effect: 6 Dose: Duration Exposure: Duration Observation: NR NR HEMOR KIDNY 6 40.000 4.0 weeks 4.0 weeks See previous record. Slight liver degeneration and focal hemorrhaglc areas In the kidneys. BMeger, 1953a RECORD #6: Species: Sex: Effect: Route: Dogs Hale PEL Capsul Dose: Duration Duration Exposure: Observation: 20.000 11.0 days 11.0 days Comment: Citation: Number Exposed: 1 Number Responses: 1 Type of Effect: DEATH SHe of Effect: BODY Severity Effect: 10 Administered as dlsodlum salt. Doses: 0.8-40 mg 1on/kg/day (1 dog/dose). Death 1n all dogs within 11 days at >20. Stomach erosion and hemorrhage at dosage >20 mg 1on/kg/day. Study summarized 1n ODW Health Advisory. BMeger, 1953b RECORD #7: Species: Sex: Effect: Route: Dogs Hale LOAEL Capsul Dose: Duration Duration Exposure: Observation: 0.800 6.0 weeks 6.0 weeks Comment: Citation: Number Exposed: 1 Number Responses: 1 Type of Effect: HYPRT SHe of Effect: COLON Severity Effect: 3 See previous record. Stomach congestion, edema of stomach and upper Intestine common 1n all dogs. Additional Information not reported. BMeger, 1953b 0168d -73- 04/19/89 ------- RECORD #8: Comment: Citation: Species: Sex: Effect: Route: Humans Hale PEL Oral (NOS) Dose: 100.000 Duration Exposure: 1.0 days Duration Observation: 1.0 days Number Exposed: 1 Number Responses: 1 Type of Effect: DEATH SHe of Effect: BODY Severity Effect: 10 / Suicide due to 1ngest1on of estimated 7-8 g of dlsodlum salt (-100 mg Ion/kg). Repeated vomiting. Focal edema and extensive hemorrhages 1n the lungs and gastrointestinal tract Al lender, 1983 RECORD #9: Species: Sex: Effect: Route: Rats Male PEL Gavage Dose: Duration Duration Exposure: Observation: 57.000 1.0 days 14.0 days Comment: Citation: Number Exposed: NR Number Responses: NR Type of Effect: DEATH Site of Effect: BODY Severity Effect: 10 1059. Peanut oil vehicle. Rats observed 14 days or until recovery. Minimum 10 rats/dose and 4 doses; design of assay with endothall not specifically reported. Galnes and Under, 1986 RECORD #10: Species: Sex: Effect: Route: Rats Female PEL Gavage Dose: Duration Duration Exposure: Observation: 46.000 1.0 days 14.0 days Comment: Citation: Number Exposed: NR Number Responses: NR Type of Effect: DEATH Site of Effect: BODY Severity Effect: 10 1059. See previous record. Galnes and Under, 1986 0168d -74- 04/19/89 ------- RECORD #11 Comment: Citation: Species: Sex: Effect: Route: Rats NR PEL Oral (NOS) Dose: 38.000 Duration Exposure: 1.0 days Duration Observation: 2.0 days Number Exposed: NR Number Responses: NR Type of Effect: DEATH SHe of Effect: BODY Severity Effect: 10 LD5Q reportedly 38-51 mg add/kg In 48 hours. Additional Information not reported. Primary source not available. .Slmslman et al., 1976; Worthing and Walker, 1983 RECORD #12: Species: Rats Sex: Femal Effect: PEL Route: Oral * Number Exposed: Number Responses Type of Effect: SHe of Effect: Severity Effect: e (NOS) 25 : 2 DEATH BODY 10 Dose: 16.000 Duration Exposure: 14.0 days Duration Observation: 14.0 days Comment: Citation: Treated on gestation days 6-19. Doses: 8, 16, 24 mg/kg/day. 25-26/group. 10 maternal deaths at 24 mg/kg/day. 2 maternal deaths at 16 mg/kg/day. No fetal developmental/toxic effects 1n surviving dams; exam day not reported. Prom ODW HA. Science Applications, Inc., 1982 RECORD #13: Species: Rats Sex: Femal Effect: NOEL Route: Oral Number Exposed: Number Responses Type of Effect: SHe of Effect: Severity Effect: e (NOS) 25 : 0 DEATH BODY 10 Dose: Duration Exposure: Duration Observation: NR NR TERAD . . FETUS 8.000 14.0 days 14.0 days Comment: Citation: See previous record. fetotoxlc effects. No maternal deaths. No teratogenlc or Science Applications, Inc., 1982 0168d -75- 04/19/89 ------- RECORD #14: Comment: Species: Sex: Effect: Route: Rats Both PEL Food Dose: Duration Exposure: Duration Observation: 100.000 128.0 days 128.0 days Citation: Number Exposed: NR Number Responses: NR Type of Effect: REPRO Site of Effect: OTHER Severity Effect: 10 / Administered as d1sodium salt. Doses: 4, 12, 100 mg Ion/kg/ day. 100 days of treatment prior to mating. Pups died within 1 week of birth and treatment discontinued. Other Indices not reported. Scientific Associates, 1965 RECORD #15: Species: Sex: Effect: Route: Rats Both LOAEL Food Dose: Duration Duration Exposure: Observation: 12.000 128.0 days 142.0 days Comment: Citation: Number Exposed: NR Number Responses: NR Type of Effect: REPRO SHe of Effect: OTHER Severity Effect: 4 See previous record. Three generation study; each generation treated for 100 days prior to mating. Reduced body weights In pups at 21 days of age. No effect on survival. Other Indices not reported. Scientific Associates, 1965 0168d -76- 04/19/89 ------- RECORD #16: Comment: Citation: Species: Sex: Effect: Route: Rats Both NOEL Food Dose: Duration Exposure: Duration Observation: 4.000 128.0 days 142.0 days Number Exposed: NR Number Responses: NR Type of Effect: REPRO SHe of Effect: OTHER Severity Effect: 4 See previous record. No effect on survival or body weight of pups. NOEL for reproductive effects but other Indices not reported. Study summarized In ODW Health Advisory. Scientific Associates, 1965 NR = Not reported 0168d -77- 04/19/89 ------- UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 29 !9R° SUBJECT: FROM: TO: Health and Environmental Effects Document for Endothall William H. Farland, Ph.D. Director Office of Health and Environmental Assessment (RD-689) Matthew Straus Chief, Waste Characterization Branch Office of Solid Waste (OS-330) I am forwarding copies of the Health and Environmental Effects Document (HEED) for Endothall. The HEEDs support listings under RCRA, as well as provide health-related limits and goals for emergency and remedial actions under CERCLA. These documents represent scientific summaries of the pertinent available data on the environmental fate and mammalian and aquatic toxicity of each chemical at an extramural effort of about $10K. The attached document has been reviewed within OHEA, by staff in OPP and OTS, and by two external scientists. „- ' Should you wish to see any of the files related tor the development of the HEEDs, please call Chris DeRosa at FTS: 684-7531. Attachment «iov } aiKMAMg) DATE ) 8FA F«M 1 3204 02^0) CONCUMINC cs OFFICU U. FILE COPY ------- |