HALOETHERS Ambient Water Quality Criteria Criteria and Standards Division Office of Water Planning and Standards U.S. Environmental Protection Agency Washington, D.C. ------- CRITERION DOCUMENT HALOETHERS CRITERIA Aquatic Life 4-bromophenylphenyl ether For 4-bromophenylphenyl ether the criterion to protect fresh- water aquatic life as derived using the Guidelines is 6.2 ug/1 as a 24-hour average and the concentration should not exceed 14 ug/1 at any time. For saltwater aquatic life, no criterion for 4-bromophenyl- phenyl ether can be derived using the Guidelines, and there are insufficient data to estimate a criterion using other procedures. Human Health There are insufficient toxicological data to calculate exposure criteria for the haloethers covered in this document. ------- Introduction Haloethers are compounds which contain an ether moiety (R-O-R) and halogen atoms attached to the aryl or alkyl groups. Chloroethers appear to be the most important halo- ethers used commercially and can be divided into two cate- gories, alpha- and non-alpha-chloroethers (EPA, 1975). Chloromethyl methyl ether (CMME) is the only alpha haloether of commercial significance and is used primarily in the » synthesis of strong base ion exchange resins used in water conditioning and for chemical separation processes. However, CMME preparations are usually contaminated with 1 to 8 per- cent bix(chloromethyl) ether (BCME) which has been demonstrat- ed to be a potent carcinogen. The beta-chloroethers are widespread environmental contaminants. It has been suggested that they are: produced or may be formed as by-products in sizable quantities, releas- ed to and appear to persist in the environment, can pass through drinking water treatment plants, and may be carcino- genic. Bis(2-chloroethyl) ether (BCE) is used as a dewaxing agent for lubricating oils and is a useful solvent for naph- thenic components (Fairhall, 1949; Jacobs and Scheflan, 1953; Pollard and Lawson, 1955; Mervart, et al. 1960). BCE has also been used to separate butadiene from butylene (Lurie, 1965). The second major use of bis(2-chloroethyl)- ether is in the textile industry as a cleaning agent, a wetting agent and penetrant in combination with diethylene glycol, sulphonated oils, etc. (Browning, 1953; Jacobs and Scheflan, 1953; Allen, 1956). The compound generally is A-l ------- a good solvent for tars, fats, waxes, oils, resins and pec- tins, and will dissolve cellulose esters when used with 10 to 30 percent ethanol (Fife and Reid, 1930). Bis(2-chloroisopropyl) ether is an excellent solvent and extractant for fats, waxes, and greases. It also finds use as a cleaning and spotting agent as well as an additive to paint and varnish removers (Hake and Rowe, 1963; Lurie, 1965). The alpha-haloethers are more reactive than beta-halo- ethers due to the two electronegative atoms (oxygen and halogen) which are bonded to the same carbon (Summers, 1955). This difference in reactivity is evident by the different rates of hydrolysis. The most commercially significant haloethers are the chloroethers. Chlorine substitution on ethers tends to increase their density, boiling point, and odor while decreasing their flammability and altering their solubility properties. The fluorine substituted com- pounds are much more volatile than their chlorinated ana- logues (EPA, 1975). The haloethers exist within a wide range of physical properties. For example, boiling points may range from 43.2°C (2,2,2-trifluroethyl vinly ether) to 310°C (4-bromo- phenylphenyl ether) (Lurie, 1965). Melting points can range from 103.5°C (chloromethyl methyl ether) to -3°C (chloro- methyl phenyl ether) (Hawley, 1971). The haloethers are very soluble in benzene, carbon tetrachloride, and acetone (Scheflan and Jacob, 1953) and miscible in all oils (Lurie, 1965). Table 1 lists the physical properties of some haloethers. A-2 ------- TABLE 1 Physical Properties of Haloethecs Ether bis (chloromethyl) bis (2-chloroethyl) (Chlorex) bis (2-chlorisopropyl) bis (2-chloroethoxy) methane Chloromethyl methyl 2- (2-chloroethoxy) ethyl •f 2-chloroethyl co dichloromethyl methyl dichloromethyl chloro- methyl bis (dichloromethyl) tr ichloromethyl methyl trichloromethyl dichloromethyl 1-chloroethyl ethyl 2-chloroethyl ethyl bis (1-chloroethyl) Structure (C1CH2)20 (C1CH2CH2)20 CH3 (C1CH2CH) 2O (C1CH2CH20)2CH2 C1CH2OCH3 C12CHOCH3 C12CHOCH2C1 C12CHOCHC12 C13COCH3 C13COCHC12 CH3CHC10C2H5 (CH,CHC1),O -3 ^ Boiling Melting Point Point (deg.C) (deg.C) 105 -41.5 178 -46.7 187.3 -96.8 to 99.8 218.1 -32.8 61 -103.5 84.5 129 143 106-110.5 159 2857mm 106 113 d20/4 1.315 1.2199 1.1127 1.234 1.0605 1.270 1.46430°C 1.558 30°C 1.4391 0.9495 0.9945 1.10625°C Vapor Solubility Pressure in water (mm Hg) (g/iO) 0.7320°C 1.07 0.71-0.8520 C 0.17 ------- TABLE 1 (continued) Ether bis (2-bromoethyl) bis (2-chloropropyl) bis (3-chloropropyl) bis (4-chlorobutyl) 2-chloroethyl vinyl •f chloromethyl ethyl chloromethyl phenyl 2,2-dichloro-l,l- difluoroethyl methyl (raethoxyflurane) 2,2,2-tnfloroethyl vinyl (fluoroxene or fluoromar) Structure (BrCH2CH2)20 (CH3CHC1CH2)20 (C1CH2CH2CH2)2O (C1CH2CH2CH2CH2)20 C1CH2CH2OCH=CHH2 C1CH2OCH2CH3 C1CH2OC6H5 CHC12CF2OCH3 CP3CH2OCH=CH2 Boiling Melting Point Point {deg.C) (deg.C) 11532mm 188 215745nun 84-865.5°C 109 -70 84 88-90 - 3 104 -35 43.2 Vapor Pressure d20/4 (nun Hg) 27°c 1.8227// (- 1.109 1.14020/20 25°C 1.0691" C 1.0493 1.0322°4 1.4262 1.13 286 Solubility in water (g/iO) 0.6 0.4 Lune, 1965; Allen, 1956; Tschamler, 1950; Krentz, 1963; Hake and Roe, 1963 ------- REFERENCES Allen, H. 1956. Safety hazards on some newer fine chemicals. Chem. Prod. Chem. News. 19: 482. Browning, E. 1953. Beta, beta-dichloroethyl ether. In Toxi- city of Industria Organic Solvents. Chemical Publishing Co., Inc., N.Y. p. 266. Fairhall, L.T. 1949. Dichloroethyl ether. In Industrial Toxicology. Willis and Wilkins Co., Baltimore. Fife, H.R., and E.W. Reid. 1930. New industrial solvents: ethylene dichlor dichloroethyl ether, and disopropyl ether. Industr. Engr. Chem. 22: 513. Hake, C.L., and U.K. Rowe. 1963. Ethers. In Industrial Hygiene and Toxicol. 2nd ed., ed. F.A. Patty. Interscience Publishers, N.Y. 2: 1655. Hawley, G.G. 1971. The Condensed Chemical Dictionary, 8th ed. Van Nostrand, Reinhold-Co., New York. Jacobs, M.B., and L. Scheflan. 1953. Oil- and water-repelling substances. Ger. Offen. 2,247,111 24 pp. Krantz, J.C., Jr. 1963. Anesthetics. Kirk-Othmer Encyclopedia ot Chemical Technology, Vol. 2, 2nd ed., John Wiley and Sons, Inc., N.Y. 2: 393. A-5 ------- Lurie, A.P. 1965. Ethers. Kirk-Othmer Encyclopedia of Chemical Technology Vol. 8, 2nd ed. John Wiley and Sons, Inc., N.Y. Mervart, Z., et al. 1960. Economic analysis of the effect of solvent characteristics on the isolation of 1,3-butadiene by extractive distillate. Chem. Prumysl. 10j 132. Pollard, W.R., and J.V. Lawson. 1955. Corrosion rates. Ind. Eng. Chem. 47. Scheflan, L., and H.B. Jacobs. 1953. The Handbook of Solvents. Van Nostra Co., Inc., New York and London. Summers, L. 1955. The alpha-haloalkyl ethers. Chem. Rev. 55: 301. Tschmaler, H. 1950. Chlorex (Bis(2-chloroethyl)ether). Osterr. Chem. Atg. 51: 145. U.S. EPA. 1975. Investigation of selected potential environ- mental contaminants: haloethers. NTIS, Off. Tox. Subst., Springfield, Virginia^ A-6 I.J ------- AQUATIC LIFE TOXICOLOGY* FRESHWATER ORGANISMS Introduction The only toxicity data for haloethers, other than for those compounds discussed in the criterion document for chloroalkyl ethers, are for 4-bromophenylphenyl ether and the bluegill, fat- head minnow/ and Daphnia magna. Acute Toxicity The bluegill has been exposed to 4-bromophenylphenyl ether and the unadjusted 96-hour LC50 is 4,940 ug/1 (Table 1). When this result is adjusted for test conditions and species sensi- tivity, a Final Fish Acute Value of 690 ug/1 is obtained. Daphnia magna is more sensitive than the bluegill with an unadjusted 48-hour EC50 of 360 ug/1 (Table 2). The Final Inver- tebrate Acute Value for 4-bromophenylphenyl ether is 14 ug/1 and this also is the Final Acute Value. *The reader is referred to the Guidelines for Deriving Water Quality Criteria for the Protection of Aquatic Life [43 FR 21506 (May 18, 1978) and 43 FR 29028 (July 5, 1978)] in order to better understand the following discussion and recommendation. The fol- lowing tables contain the appropriate data that were found in the literature, and at the bottom of each table for the calculations for deriving various measures of toxicity as described in the Guidelines. B-l ------- Chronic TOxicity A chronic value for 4-brcmophenylphenyl ether, 61 ug/1, is derived from an embryo-larval test with the fathead minnow in which adverse effects on survival and growth were observed (Table 3) (U.S. EPA, 1978). After division by the species sensitivity factor (6.7), a Final Fish Chronic Value of 9.1 ug/1 is derived. Since no other chronic value for an invertebrate or plant species or a Residue Limited Toxicant Concentration is available, 9.1 ug/1 is also the Final Chronic Value. B-2 ------- CRITERION FORMULATION Freshwater-Aquatic Life Summary of Available Data The concentrations below have been rounded to two significant figures. i 4-bromophenylphenyl ether Final Fish Acute Value = 690 ug/1 Final Invertebrate Acute Value = 14 ug/1 Final Acute Value = 14 ug/1 Final Fish Chronic Value = 9.1 ug/1 Final Invertebrate Chronic Value = not available Final Plant Value = not available Residue Limited Toxicant Concentration = not available Final Chronic Value = 9.1 ug/1 0.44 x Final Acute Value = 6.2 ug/1 The maximum concentration of 4-bromophenylphenyl ether is the Final Acute Value of 14 ug/1 and the 24-hour average concentration is 0.44 times the Final Acute Value. No important adverse effects on freshwater aquatic organisms have been reported to be caused by concentrations lower than the 24-hour average concentration. CRITERION: For 4-bromophenylphenyl ether the criterion to protect freshwater aquatic life as derived using the Guidelines is 6.2 ug/1 as a 24-hour average and the concentration should not exceed 14 ug/1 at any time. B-3 ------- 0) I Table 1. Freshwater fish acute values for haloethers (U.S. EPA, 1978) Adjusted Bioaseay Test Chemical Time LCbu Lcbo Organism M^t-nod* Conct** Description tfera) Blueglll. S U 4-Bromophenyl- 96 4,940 2,700 Lepomts macrochirua phenyl ether * S • static ** U - unmeasured Geometric mean of adjusted values: A-Bromophenylphenyl ether *• 2,700 Mg/1 ^ S • 690 pg/1 ------- CD I U1 Table 2 Freshwater invertebrate acute values for haloethers (U.S. EPA, 1978) Organism Cladoceran, Daphnia magna Bioassay Test Chemical Method* Cone,** Description S U 4-Bromophenyl- phenyl ether Time itllB) 48 LCbU (uq/1) 360 Adjusted LC50 (uq/1) 300 * S = static ** U = unmeasured Geometric mean of adjusted values: 4-Bromophenylphenyl ether = 300 ug/1 ------- Tafcle 3 Freshwater fish chronic values for haloethers (U.S. EPA. 1978) Chronic Limits Value Organism Test* (ug/il (ug/il 4-BromophenylphenyI ether Fathead minnow. E-L 89-167 61 Pimephales promelas * E-L = embryo-larva Geometric mean of chronic values - 61 pg/1 g—j =9.1 pg/1 Lowest chronic value - 61 Mg/1 CTv ------- CRITERION FORMULATION Saltwater-Aquatic Life Summary of Available Data No appropriate data are available for saltwater organisms and any haloether other than those discussed in the criterion document for chloroalkyl ethers. CRITERION: No saltwater criterion can be derived for any haloether using the Guidelines because no Final Chronic Value for either fish or invertebrate species or a good substitute for either value is available, and £here are insufficient data to estimate a criterion using other procedures. B-7 ------- HALOETHERS REFERENCES U.S. EPA. 1978. In-depth studies on health and environmental impacts of selected water pollutants. U.S. Environ. Prot. Agency, Contract No. 68-01-4646. B-8 ------- Mammalian Toxicology and Human Health Effects I. Introduction The EPA is currently charged with establishing water quality criteria for halogenated ethers. This document covers chlorinated aromatic ethers including: chlorophenyl phenyl ethers bromophenyl phenyl ethers polychlorinated diphenyl ethers A separate document in this series, entitled "Chloroalkyl ethers," covers the following compounds: bis(chloromethyl)ether bis(2-chloroethyl)ether 2-chloroethyl vinyl ether bis(2-chloroisopropyl)ether bis(2-chloroethoxy)methane C-l ------- II. Exposure A. Ingestion 1. Water Qualitative identifications of several haloethers in raw and finished water have been reported. This information is summarized in Table 1. The nomenclature used in specifying some haloethers creates a certain amount of confusion in evaluating these monitoring data. For instance, in Table 1, pentachlorophenoxy methyl ether is probably the same as pentachlorophenyl methyl ether. The names used in Table 1 are those given in the various references cited. Shackelford and Keith (1976) have compiled information on the frequency of organic compounds identified in water. This information was taken from both the published literature and unpublished results of survey analyses from EPA Regional Laboratories and Research Laboratories. Although actual levels of the haloethers in waters are not specified, a breakdown is given of the various types of waters found to be contaminated. This infor- mation is presented in Table 2. The study by Ewing and coworkers (1977) is based on the anal- ysis of 204 water samples collected from fourteen heavily industrialized river basins. As indicated in Table 1, pentachlorophenyl methyl ether was found in 12 samples (5.88%), with other chlorophenyl ethers found less frequently. As Indicated above, the reports of "pentachlorophenoxy methyl ether" probably refer to pentachlorophenyl methyl ether. The studies by Friloux (1971) and the U.S. Environmental Protection Agency (1972) both summarized in Table 1, were conducted in the New Orleans area. C-2 ------- Table 1. Haloethers Qualitatively Identified in Water (see text for details) Reference Haloether * vO a\ 1 •a o Jl CJ 5 en ff o l-l •H £ CO • S3 Bromophenyl phenyl ether Bis(4-chlorophenyl)ether Dichlorophenyl chlorophenyl ether 2,4,4'-Trichloro-2'-hydroxy- dlphenyl ether Dichlorophenyl methyl ether Trichlorophenyl methyl ether Tetrachlorophenyl methyl ether Fentachlorophenyl methyl ether Pentachlorophenoxy methyl ether 5 2 2 10 1 5 1 12 2 Frequency of occurrence. C-3 ------- Table 2. Frequency Haloethers Identified in Various Types of Water (Shackelford and Keith, 1976) Water Type Contaminated FDW River Raw Water Bromophenyl phenyl ether 3 2 Bis (4-chlorophenyl) ether Dichlorophenyl chlorophenyl ether 2,4,4' -Tr ichloro-2 ' -hydroxy- diphenyl ether Pentachlorophenyl methyl ether 331 Effluent CHEM RS 2 2 1 1 from: STP 2 Key FDW - Finished drinking water G8SK m Chemical plant RS » Raw sewage STP - Sewage treatment plant C-4 ------- In the 1975 National Organics Reconnaissance Survey by the U.S. Environmental Protection Agency, no halo- ethers were found in the waters of Miami, Florida; Seattle, Washington; Ottumwa, Iowa; or Cincinnati, Ohio (U.S. EPA, 1975). 2. Food No monitoring data have been found on the levels of haloethers in food. A bioconcentration factor (BCF) relates the concentra- tion of a chemical in water to the concentration in aquatic organisms, but BCF's are not available for the edible portions of all four major groups of aquatic organisms consumed in » the United States. Since data indicate that the BCF for lipid-soluble compounds is proportional to percent lipids, BCF's can be adjusted to edible portions using data on percent lipids and the amounts of various species consumed by Americans, A recent survey on fish and shellfish consumption in the United States (Cordle et al., 1978) found that the per capita consumption is 18.7 g/day. From the data on the nineteen major species identified in the survey and data on the fat content of the edible portion of these species (Sidwell, et al., 1974), the relative consumption of the four major groups and the weighted average percent lipids for each group can be calculated: C-5 ------- Consumption Weighted Average Group (Percent) Percent Lipids Freshwater fishes 12 4.8 Saltwater fishes 61 2.3 Saltwater molluscs 9 1.2 Saltwater decapods 18 1.2 Using the percentages for consumption and lipids for each of these groups, the weighted average percent lipids is 2.3 for consumed fish and shellfish. Neither measured steady-state bioconcentration factors {BCF) nor laboratory data (octanol-water partition coefficient) are available for estimation of BCF at this time. B. Inhalation No monitoring information is available on the levels of any chloroethers in ambient air. C. Dermal Because of the lack of monitoring data, no evalua- tion of the importance of dermal exposures can be made for the haloethers. C-6 ------- III. Pharmacokinetics No information has been encountered in the pharnacokinetics of the haloethers under review. C-7 ------- IV. Effects 1. Acute, Subacute, and Chronic The acute and subacute oral toxlcity of various chlorinated phenyl ethers is summarized in Tables 3 and 4. Because of the lack of experimental detail presented in this summary of unpublished data by Hake and Rove (1963) these results are difficult to interpret. However, the reported results on "highly purified" pentachlorophenyl ether compared to the other pentachloro- phenyl ether suggest that Impurities may be major toxic constituents. Hake and Rowe (1963) report that "small amounts" of hexachloro- diphenyl ether may cause acneform dermatitis in man. 2. Joint Action with Other Toxicants No Information is available. 3. Teratogenicity Ho information is available. 4. Mutagenicity No information is available. 5. Carcinogenicity No Information is available. C-8 ------- Table 3. Chlorinated Phenyl Ethers Summary of Single-Dose Oral Feeding Studies on Guinea Pigs (Hake and Rowe, 1963) Total Number of Chlorines 1 x Cl 2 x Cl 3 x Cl 4 x Cl 5 x Cl 6 x Cl After 4 Lethal dose (mg/kg) 700 1,300 2,200 3,000 3,400 3,600 days Survival dose (mg/kg) 200 400 400 400 1,800 400 After Lethal dose (mg/kg) 600 1,000 1,200 50 100 50 30 days Survival dose (mg/kg) 100 50 200 0.5 5 5 C-9 ------- Table A. Chlorinated Phenyl Ethers: Results of Repeated Oral Feeding of Rabbits (Hake and Rove, 1963) Total Number of Chlorines 1 2 3 4 5 6 Dose (mg/kg) 100 100 100 50 10 50 5 50 100** 10** 1** 5 1 0.1 Number of doses 19 19 5 20 20 4 20 8 20 20 20 8 20 20 Number days 29 29 12 29 29 10 29 21 29 29 29 10 28 28 of Effect None Mild liver injury Death Slight liver injury No effect Death Severe liver injury Death Moderate liver injury No growth Slight liver injury No effect Death Severe liver injury No effect Animals dosed 5 days/week x 4 weeks unless death intervened. Vehicles not specified. ** Highly purified pentachlorophenyl ether. C-10 ------- V. Criterion Rationale A. Existing Standards The Occupational Safety and Health Administration (38 FR 23540) has 2 ' set a time-weighted average value of 500 yg/m for the following aromatic chloroethers in the air of the working environment: monochlorophenyl phenyl ether, dichlorophenyl phenyl ether, tricolorophenyl phenyl ether, tetrachloro- phenyl phenyl ether, and pentachlorophenyl phenyl ether. This value has also been adopted by the American Conference of Governmental and Industrial Hygienistd (ACGIH, 1974). The standard is designed to prevent the formation of chloracne in exposed workers. B. Current Levels of Exposure As detailed in Section II, only limited information is available on the extent of human exposure to haloethers in water and no information is available on ambient levels of haloethers in air or food. Quantitative estimates of human exposure cannot be made. C. Special Groups at Risk Individuals working with haloethers or living in areas where these haloethers are produced are probably at greater risk than the general popu- lation. D. Basis for the Standard As indicated in Section V.A., the TLV for chlorophenyl phenyl ethers 2 is 500 jjg/m . By a process analogous to that used by Stokinger and Woodard (1958), this standard could be used to calculate a water criterion. However, since the TLV for these compounds is based on preventing chloracne, rather than chronic toxicity, such a calculation would not be appropriate. C-ll ------- There are not sufficient toxicologic data to calcu- late exposure criteria for other haloethers covered in this document. C-12 ------- REFERENCES AC6IH (American Conference of Governmental Industrial Hygienlsts) (1974), Documentation of the Threshold Limit Values, 3rd Edition, 2nd Printing. Eving, B.B., E.S.K. Chian, J.C. Cook, C.A. Evans, P.K. Hopke, and E.G. Perkins (1977), Monitoring to Detect Previously Unrecognized Pollutants in Surface Waters, EPA 560/6-77-015, 75 pp. Friloux, J. (1971), "Petrochemical Wastes as a Pollution Problem in the Lower Mississippi River," Paper submitted to the Senate Subcommittee on Air and Water Pollution, April 5. Hake, C.L. and V.K. Rowe (1963), "Ethers," in Industrial Hygiene and Toxicology, 2nd Edition, Patty, F.A. (ed.), Interscience Publishers, New York, ,2:1655- 1718. Rosen, A.A., R.T. Skeel, and M.B. Ettinger (1963), "Relationship of River Water Odor to Specific Organic Contaminants," J. Water Pollut. Contr. Fedr., .35:777-782. Shackelford, W.M. and L.H. Keith (1976), Frequency of Organic Compounds Identified in Water, EPA-600/4-76-062, U.S. Environmental Protection Agency, Athens, GA., 626 pp. Stoklnger, H.E. and R.L. Woodward (1958), "Toxlcologlc Methods for Establishing Drinking Water Standards," J. Amer. Water Works Assn., 50;515. U.S. Environmental Protection Agency (1972), "Industrial Pollution of the Lower Mississippi River in Louisiana," Region VI, Dallas, Texas, Surveillance and Analysis Division. U.S. Environmental Protection Agency (1975), Preliminary Assessmei £ of Sus- pected Carcinogens in Drinking Water; Interim Report to Coiu cess, Washington, D.C. C-13 ------- |