C = Cornman (1950) CARBAMATES, DITHIO 9/ 1993 119 CARBAMATES, DITHIO 9/ 1993 120 SAR CARBAMATES, DIOTHIO Includes N, N dialkyldithiocarbamates and ethylenebisdithiocarbamates and their metal salts which include but are not limited to Zn, Na, Fe, Mn, Cu, Pb, Hg, Ag, and Se. The SARs for the dithiocarbamates and their degradation products are sigmoidal with acute and chronic toxicity increasing with increasing Kow. The sigmoidal relationship between Kow and toxicity is very poor statistically. Consequently, toxicity predictions must be made using either the closest analog or averaging data for the two closest analogs which bracket the dithiocarbamate under question. CARBAMATES, DITHIO 9/ 1993 121 CROWN ETHERS 9/ 1993 122 SAR CROWN ETHERS Use SAR for NEUTRAL ORGANICS for fish and daphnids; some should show excess toxicity toward green algae due to over chelation of nutrient elements; each crown ether chelates a different element; the type of element chelated by a crown ether has to be matched up with a nutrient element needed by algae, e. g, Fe, Ca, Mg. There are no test data to show that crown ethers do in fact overchelate nutrient elements in the algal toxicity test. Conclusions about crown ethers are based on extrapolations of theory. CROWN ETHERS 9/ 1993 123 DIAZONIUMS, AROMATIC 9/ 1993 124 SAR DIAZONIUMS, AROMATIC Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 2.456  0.331 log Kow Statistics: N = 3; R 2 = 0.98 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for aromatic diazoniums.

Limitations: If the log Kow value is greater than 8.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: United States Environmental Protection Agency (USEPA). 1991. OTS TSCA 8( e) database. Washington, DC: USEPA, Office of Toxic Substances.

LIST OF AROMATIC DIAZONIUMS USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 4 Dimethylamino benzene diazonium 0.150 2.1 EPA 4 Dimethylamino benzene diazonium 0.330 2.1 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991). DIAZONIUMS, AROMATIC 9/ 1993 125 EPOXIDES, MONO 9/ 1993 126 SAR EPOXIDES, MONO Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 0.290  0.382 log Kow Statistics: N = 4; R 2 = 0.92 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for monoepoxides.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

Monoepoxides which are significantly more toxic than predicted by this SAR, based on the fish 14 d LC50 SAR, are:

epichlorohydrin, and epibromohydrin.

Endrin has an excess toxicity of over 33,000 times the value predicted by this SAR. Diepoxides are significantly more toxic than predicted by this SAR and a SAR for diepoxides has been developed.

References: Bridie AL, Wolff CJM, and Winter M. 1979. The acute toxicity of some petrochemicals to goldfish. Water Research, 13: 623 626.

Conway RA, Waggy GT, Speigel MH, and Berglund RL. 1983. Environmental fate and effects of ethylene oxide. Environmental Science and Technology 17: 107 112.

Leach JM and Thakore AN. 1975. Isolation and identification of constituents toxic to juvenile rainbow trout (Salmo gairdneri) in caustic extraction effluents from kraft pulpmill bleach plants. Journal of the Fisheries Research Board of Canada, 32: 1249.

United States Environmental Protection Agency (USEPA). 1986. Water Quality Criteria for 1986. Washington, DC: USEPA. EPOXIDES, MONO 9/ 1993 127 LIST OF MONOEPOXIDES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ MONOEPOXIDES USED IN CALCULATION OF THE SAR Ethylene oxide 84.0 0.8 C Allyl glycidyl ether 30.0 0.33 B Phenyl glycidyl ether 43.0 1.12 B 9,10 Epoxystearic acid 1.5 5.14 LT MONOEPOXIDES HAVING EXCESS TOXICITY Endrin 0.000410 2.9 W ____________________________________________________________________________________ ____

B = Bridie et al. (1979) C = Conway et al (1983) LT = Leach and Thakore (1975) W = USEPA (1986); water quality criteria document EPOXIDES, MONO 9/ 1993 128 SAR EPOXIDES, MONO Organism: Fish Duration: 14 d Endpoint: LC50 (Mortality)

Equation: Log 14 d LC50 (mM/ L) = 0.49506  0.34618 log Kow Statistics: N = 9; R 2 = 0.87 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for monoepoxides.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

Monoepoxides which are significantly more toxic than predicted by this SAR are:

epichlorohydrin, 53 X excess toxicity; and epibromohydrin, 57 X excess toxicity.

Diepoxides are significantly more toxic than predicted by this SAR and a SAR for diepoxides has been developed.

References: Deneer JW, Sinnige TL, Seinen W, and Hermens JLM. 1988. A quantitative structure activity relationship for the acute toxicity of some epoxy compounds to the guppy. Aquatic Toxicology 13: 195 204. EPOXIDES, MONO 9/ 1993 129 LIST OF MONOEPOXIDES USED TO DEVELOP THE FISH 14 d LC50 SAR.________________________________________________________________________________ ________ 14 d LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ MONOEPOXIDES USED IN CALCULATION OF THE SAR Glycidol 50.0 1.46 D Propylene oxide 31.9 0.27 D 1,2 Epoxybutane 32.9 0.26 D Styrene oxide 7.07 0.73 D 1,2 Epoxyhexane 18.6 1.31 D 1,2 Epoxyoctane 10.4 2.37 D 1,2 Epoxydecane 3.26 3.43 D 1,2 Epoxydodecane 1.11 4.49 D 1,2 Epoxyhexadecane * 6.60 D MONOEPOXIDES HAVING EXCESS TOXICITY Epichlorohydrin 0.651 0.21 D Epibromohydrin 0.807 0.07 D ____________________________________________________________________________________ ____

* No fish mortality in saturated solutions.

D = Deneer et al (1988) EPOXIDES, MONO 9/ 1993 130 SAR EPOXIDES, MONO Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 0.036  0.567 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for monoepoxides.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: Conway RA, Waggy GT, Speigel MH, and Berglund RL. 1983. Environmental fate and effects of ethylene oxide. Environmental Science and Technology 17: 107 112.

LIST OF MONOEPOXIDES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Ethylene oxide 137.0 0.8 C ____________________________________________________________________________________ ____

C = Conway et al. (1983) EPOXIDES, MONO 9/ 1993 131 EPOXIDES, DI 9/ 1993 132 SAR EPOXIDES, DI Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 1.184  0.263 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for diepoxides and other polyepoxides.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: Bailey RE and Rhinehart WL. 1976. Evaluation of D. E. R. 331, diglycidyl ether of bisphenol A, in the aquatic environment. R& D Report D0004653. Midland, MI: The Dow Chemical Company.

United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: USEPA, Office of Toxic Substances.

LIST OF DIEPOXIDES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Diglycidyl ether of bisphenol A 3.1 3.1 B Chemical identity CBI * 7.1 EPA ____________________________________________________________________________________ ____

* No fish mortality in saturated solutions.

B = Bailey and Rhinehart (1976) EPA = USEPA (1991); chemical identity is Confidential Business Information under TSCA. EPOXIDES, DI 9/ 1993 133 EPOXIDES, DI 9/ 1993 134 SAR EPOXIDES, DI Organism: Fish Duration: 14 d Endpoint: LC50 (Mortality)

Equation: Log 14 d LC50 (mM/ L) = 1.5692  0.1216 log Kow Statistics: N = 3; R 2 = 0.83 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for diepoxides and other polyepoxides.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: Deneer JW, Sinnige TL, Seinen W and Hermens JLM. 1988. A quantitative structure activity relationship for the acute toxicity of some epoxy compounds to the guppy. Aquatic Toxicology 13: 195 204.

LIST OF DIEPOXIDES USED TO DEVELOP THE FISH 14 d LC50 SAR. ____________________________________________________________________________________ ____ 14 d LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 1,3 Butadiene diepoxide 2.66 1.84 D 1,2,7,8 Diepoxyoctane 6.64 0.18 D ____________________________________________________________________________________ ____

D= Deneer et al (1988) EPOXIDES, DI 9/ 1993 135 EPOXIDES, DI 9/ 1993 136 SAR EPOXIDES, DI Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 2.093  0.1474 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for diepoxides and other polyepoxides.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: Bailey RE and Rhinehart WL. 1976. Evaluation of D. E. R. 331, diglycidyl ether of bisphenol A, in the aquatic environment. R& D Report D0004653. Midland, MI: The Dow Chemical Company.

LIST OF DIEPOXIDES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Diglycidyl ether of bisphenol A 0.95 3.1 B ____________________________________________________________________________________ ____

B = Bailey and Rhinehart (1976) EPOXIDES, DI 9/ 1993 137 ESTERS 9/ 1993 138 SAR ESTERS Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 0.535 log Kow + 0.25 Statistics: N = 29; R 2 = 0.828 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for the following esters:

1. Acetates 2. Benzoates 3. Dicarboxylic aliphatics 4. Phthalates derived from aliphatic alcohols and phenol.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: Veith GD, DeFoe D, and Knuth M. 1984. Structure activity relationships for screening organic chemicals for potential ecotoxicity effects. Drug Metabolism Reviews 15( 7): 1295 1303. ESTERS 9/ 1993 139 LIST OF ESTERS USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Methylene chloride 322.895 1.25 Z Methyl acetate 320.0 0.18 V Ethyl acetate 230.0 0.69 V 2 Ethoxyethyl acetate 42.2 0.71 V Diethyl malonate 14.9 1.19 V Ethyl p aminobenzoate 35.2 1.22 V Propyl acetate 60.0 1.25 V Methyl 2,4 dihydroxybenzoate 38.5 1.59 V Butyl acetate 18.0 1.79 V Diethyl adipate 19.3 1.80 V Methyl p nitrobenzoate 23.6 2.10 V Dimethyl 2 nitro p phthalate 6.52 2.28 V Methyl 4 chloro 2 nitrobenzoate 27.2 2.35 V Dimethyl 2 amino p phthalate 8.94 2.65 V Diethyl o phthalate 30.0 2.69 V Hexyl acetate 4.40 2.87 V Ethyl hexanoate 8.90 2.87 V Methyl p chlorobenzoate 10.9 3.15 V Methyl 2,5 dichlorobenzoate 13.8 3.45 V Ethyl salicylate 19.6 3.45 V Dibutyl succinate 4.45 3.65 V Dibutyl adipate 3.66 3.96 V Diethyl sebacate 2.75 3.96 V Di n butyl o phthalate 1.10 4.74 V Di n butyl m phthalate 0.90 5.07 V Diphenyl 1 phthalate 0.80 7.06 V Di 2 ethylhexyl o phthalate * 7.06 V Di n octyl o phthalate * 7.06 V Di n octyl m phthalate * 7.06 V Di n octyl p phthalate * 7.06 V ____________________________________________________________________________________ ____

* = No fish mortality in saturated solutions.

V = Veith et al (1984) ESTERS 7/ 1988 140 SAR ESTERS Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: To find the estimated acute toxicity of an ester, use the neutral organics daphnid 48 h LC50 SAR.

Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: The daphnid 48 h LC50 SAR for neutral organics may be used to estimate acute toxicity for esters. The neutral organic 48 h LC50 SAR for daphnids may be used for other esters; however, a separate SAR has been developed for phthalate esters.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: Kuhn R, Pattard M, Pernack K D, and Winter A. 1989. Results of the harmful effects of selected water pollutants (anilines, phenols, aliphatic compounds) to Daphnia magna. Water Research 23: 495 499.

United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, USEPA.

LIST OF ESTERS USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Methylene chloride 322.895 1.25 Z Chloroacetic ethyl ester 1.6 ? K Chemical identity CBI 3.32 3.7 EPA Chemical identity CBI * 4.4 EPA ____________________________________________________________________________________ ____

* = No daphnid mortality in saturated solutions.

EPA = USEPA (1991); chemical identities are Confidential Business Information under TSCA. K = Kuhn et al (1989) ESTERS 7/ 1988 141 ESTERS 7/ 1988 142 ESTERS 7/ 1988 143 SAR ESTERS Organism: Green Algae Duration: 96 h Endpoint: EC50 (Growth)

Equation: Log EC50 (mM/ L) = 0.881  0.519 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 6.4 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for esters.

Limitations: If the log Kow value is greater than 6.4, or if the compound is solid and the EC50 exceeds the water solubility, no effects expected at saturation.

References: United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, USEPA.

LIST OF ESTERS USED TO DEVELOP THE GREEN ALGAE 96 h EC50 SAR. ____________________________________________________________________________________ ____ 96 h EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Chemical identity CBI 0.410 3.7 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991); chemical identities are Confidential Business Information under TSCA. ESTERS 7/ 1988 144 ESTERS 7/ 1988 145 SAR ESTERS Organism: Green Algae Duration: 16 d Endpoint: Chronic Value (Growth)

Equation: Log ChV (mM/ L) = 1.01  0.51 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for esters.

Limitations: If the log Kow value is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

References: United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, USEPA.

LIST OF ESTERS USED TO DEVELOP THE GREEN ALGAE CHRONIC VALUE (ChV) SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Chemical identity CBI 0.390 3.7 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991); chemical identities are Confidential Business Information under TSCA. ESTERS 7/ 1988 146 ESTERS, MONO, ALIPHATIC 9/ 1993 147 SAR ESTERS, MONO Organism: Fish Duration: 32 d Endpoint: Chronic Value (Survival/ Growth)

Equation: Log ChV (mM/ L) = 0.421  0.828 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for aliphatic monoesters.

Limitations: If the log Kow value is greater than 8.0, no effects expected at saturation.

References: United States Environmental Protection Agency (USEPA). 1991. Fish Chronic Toxicity Data Base. Duluth, MN: Environmental Research Laboratory (ERL), Office of Research and Development, USEPA, 6201 Congdon Boulevard, 55804; contact C. L. Russom (218) 720 5500.

LIST OF ALIPHATIC MONOESTERS USED TO DEVELOP THE FISH CHRONIC VALUE (ChV) SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Methyl acetate 133.0 0.2 D ____________________________________________________________________________________ ____

D = USEPA (1991) ESTERS, MONO, ALIPHATIC 9/ 1993 148 ESTERS, DI, ALIPHATIC 9/ 1993 149 SAR ESTERS, DI Organism: Fish Duration: 32 d Endpoint: Chronic Value (Survival/ Growth)

Equation: Log ChV (mM/ L) = 1.677  0.565 log Kow Statistics: N = 3; R 2 = 1.0 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for aliphatic diesters.

Limitations: If the log Kow value is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

References: United States Environmental Protection Agency (USEPA). 1991. Fish Chronic Toxicity Data Base. Duluth, MN: Environmental Research Laboratory (ERL), Office of Research and Development, USEPA, 6201 Congdon Boulevard, 55804; contact C. L. Russom (218) 720 5500.

LIST OF ALIPHATIC DIESTERS USED TO DEVELOP THE FISH CHRONIC VALUE (ChV) SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Diethyl malonate 0.759 1.1 D Dibutyl fumerate 0.030 3.9 D ____________________________________________________________________________________ ____

D = USEPA (1991) ESTERS, DI, ALIPHATIC 9/ 1993 150 ESTERS, PHOSPHATE 9/ 1993 151 SAR ESTERS, PHOSPHATE Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 0.0695  0.5178 log Kow Statistics: N = 16; R 2 = 0.595 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate the toxicity of phosphate esters and other tri alkyl phenyl phosphate esters. This SAR may be used to estimate toxicity for the following classes of phosphate esters all of which are weak acetylcholinesterase inhibitors:

1. Tri alkyl phosphate esters 2. Tri phenyl phosphate esters 3. Halogenated tri alkyl phosphate esters 4. Halogenated tri phenyl phosphate esters Some halogenated tri alkylphosphate esters are significantly more toxic than predicted by this SAR as a result of their strong acetylcholinesterase and cholinesterase inhibition. These include:

1. 1,2 dibromoethyldiethyl phosphate ester  400 X 2. 1,2 dichloroethyldiethyl phosphate ester  .30 X Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, USEPA. ESTERS, PHOSPHATE 9/ 1993 152 LIST OF PHOSPHATE ESTERS USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Tris( betachloroethyl) 210.0 0.92 EPA Tris( betachloroethyl) 90.0 0.92 EPA Chemical identity CBI 21.0 1.80 EPA Tris( dichloropropyl) 3.6 2.67 EPA Tris( dichloropropyl) 5.1 2.67 EPA Tris( 2,3 dibromopropyl) 1.33 3.51 EPA Tris( 2,3 dibromopropyl) 1.45 3.51 EPA Tributyl 11.0 3.53 EPA Tributyl 8.18 3.53 EPA Tributyl 8.8 3.53 EPA Tributyl 9.6 3.53 EPA Tributyl 11.8 3.53 EPA Tributyl 11.4 3.53 EPA Triphenyl 0.87 4.63 EPA Triphenyl 0.70 4.63 EPA Triphenyl 1.2 4.63 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991) ESTERS, PHTHALATE 9/ 1993 153 SAR ESTERS, PHTHALATE Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Use the ester fish 96 h SAR to determine the acute toxicity of a phthalate ester.

Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: The ester SAR may be used to estimate the toxicity of phthalate esters. The ester SAR is applicable for the following phthalate esters:

1. Aliphatic diesters 2. Aromatic diesters 3. Aliphatic aromatic diesters 4. Phthalates, derived from aliphatic alcohols and phenol.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturationse SAR with longer exposure.

References: Veith GD, DeFoe D, and Knuth M. 1984. Structure activity relationships for screening organic chemicals for potential ecotoxicity effects. Drug Metabolism Reviews 15( 7): 1295 1303.

LIST OF PHTHALATE ESTERS USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Dimethyl 2 nitro p phthalate 6.52 2.28 V Dimethyl 2 amino p phthalate 8.94 2.65 V Diethyl o phthalate 30.0 2.69 V Di n butyl o phthalate 1.10 4.74 V Di n butyl m phthalate 0.90 4.74 V Diphenyl i phthalate 0.80 5.07 V Di 2 ethylhexyl o phthalate * 7.06 V Di n octyl o phthalate * 7.06 V Di n octyl m phthalate * 7.06 V Di n octyl p phthalate * 7.06 V ESTERS, PHTHALATE 9/ 1993 154 ____________________________________________________________________________________ ____

* No fish mortality in saturated solutions.

V = Veith et al (1984). ESTERS, PHTHALATE 9/ 1993 155 SAR ESTERS, PHTHALATE Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Use the neutral organic daphnid 48 h SAR to determine the acute toxicity of a phthalate ester.

Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: The neutral organic SAR may be used to estimate the toxicity of phthalate esters. The neutral organic SAR is applicable for the following phthalate esters:

1. Aliphatic diesters 2. Aromatic diesters 3. Aliphatic aromatic diesters 4. Phthalates, derived from aliphatic alcohols and phenol.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, use SAR with longer exposure.

References: Nabholz JV. 1987. The acute and chronic toxicity of dialkyl phthalate esters to daphnids. Interagency memorandum to "Whom It May Concern." Washington, DC: Environmental Effects Branch, Health and Environmental Review Division, Office of Toxic Substances, United States Environmental Protection Agency. ESTERS, PHTHALATE 9/ 1993 156 LIST OF PHTHALATE ESTERS USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Methylene chloride 322.895 1.25 Z Dimethyl >52.0 1.52 N Diethyl 90.0 2.57 N Di n butyl ortho 3.4 4.69 N Di n butyl ortho 5.2 4.69 N Butyl benzyl 1.83 4.87 N Butyl benzyl 3.7 4.87 N Butyl benzyl 1.6 4.87 N Butyl benzyl 1.0 4.87 N Butyl benzyl 2.4 4.87 N Butyl benzyl 1.7 4.87 N Dihexyl * 6.80 N Butyl 2 ethylhexyl * 7.93 N Di( n hexyl, n octyl, n decyl) * 8.57 N Di( 2 ethylhexyl) * 8.66 N Di( 2 ethylhexyl) * 8.66 N Diisooctyl * 8.66 N Di( n octyl) * 8.92 N Di( heptyl, nonyl, undecyl) * 9.59 N Diisononyl * 9.72 N Diisodecyl * 10.78 N Diisodecyl * 10.78 N Diundecyl * 12.10 N Ditridecyl * 14.21 N ____________________________________________________________________________________ ____

* No daphnid mortality in saturated solutions.

N = Nabholz (1987). ESTERS, PHTHALATE 9/ 1993 157 SAR ESTERS, PHTHALATE Organism: Daphnid Duration: 21 d Endpoint: No Effect Concentration (NEC) (Reproduction)

Equation: Log 21 d NEC (mM/ L) = 0.05  0.72 log Kow Statistics: ;

Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: The neutral organic 16 d NEC SAR may be used to estimate the toxicity of phthalate esters. The neutral organic SAR is applicable for the following phthalate esters:

1. Aliphatic diesters 2. Aromatic diesters 3. Aliphatic aromatic diesters 4. Phthalates, derived from aliphatic alcohols and phenol.

Limitations: If the log Kow value is greater than 8.0, or if the compound is solid and the NEC exceeds the water solubility, no effects expected at saturation.

References: Nabholz JV. 1987. The acute and chronic toxicity of dialkyl phthalate esters to daphnids. Interagency memorandum to "Whom It May Concern." Washington, DC: Environmental Effects Branch, Health and Environmental Review Division, Office of Toxic Substances, United States Environmental Protection Agency. ESTERS, PHTHALATE 9/ 1993 158 LIST OF PHTHALATE ESTERS USED TO DEVELOP THE DAPHNID 21 d NEC SAR. ____________________________________________________________________________________ ____ 21 d NEC Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Methylene chloride 322.895 1.25 Z Dimethyl 15.0 1.52 N Diethyl 38.0 2.57 N Di n butyl ortho 1.0 4.69 N Di n butyl ortho 1.4 4.69 N Di n butyl ortho 1.5 4.69 N Butyl benzyl 0.63 4.87 N Butyl benzyl 0.44 4.87 N Di n butyl iso 0.15 5.53 N Di n butyl tere 0.32 5.53 N Dihexyl * 6.80 N Butyl 2 ethylhexyl * 7.93 N Di( n hexyl, n octyl, n decyl) * 8.57 N Di( 2 ethylhexyl) * 8.66 N Di( 2 ethylhexyl) * 8.66 N Diisooctyl * 8.66 N Di( n octyl) * 8.92 N Di( heptyl, nonyl, undecyl) * 9.59 N Diisononyl * 9.72 N Diisodecyl * 10.78 N Diisodecyl * 10.78 N Diundecyl * 12.10 N Ditridecyl * 14.21 N ____________________________________________________________________________________ ____

* No daphnid systemic effects in saturated solutions.

N = Nabholz (1987). HYDRAZINES 9/ 1993 159 SAR HYDRAZINES Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 1.53  0.438 log Kow Statistics: N = 9; R 2 = 0.91 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for:

hydrazines hydrazones hydrazides thiohydrazides semicarbazides thiosemicarbazides semicarbazones thiosemicarbazones For hydrazines with missing fragment constants in CLOGP the following constants may be used:

1. missing fragment ( C(= S)): 0.24 2. missing fragment ( NC(= O) N N): 3.13 3. missing fragment (C= NNC(= O) N): 3.39.

Limitations: Hydrazines which are 10 times less toxic than predicted by this SAR are those hydrazines which have a carboxylic acid substitution:

butanedioic acid mono( 2,2' dimethylhydrazide).

If the log Kow value is greater than 5.0 and less than 6.6, use the neutral organics fish 14 d LC50 SAR; and if the log Kow value is equal to or greater than 6.6, use the neutral organics fish ChV SAR.

References: Buccafusco RJ, Ells SJ, and LeBlanc GA. 1981. Acute toxicity of priority pollutants to bluegill (Lepomis macrochirus). Bulletin of Environmental Contamination and Toxicology 26: 446 452.

Hammermeister D, Kahl M, and Broderius S. 1990. EEB/ ERL Duluth interaction on various join projects. Duluth, MN: Environmental HYDRAZINES 9/ 1993 160 Research Laboratory Duluth, United States Environmental Protection Agency, 6201 Congdon Blvd., 55804, Unpublished memorandum to V. Nabolz.

Odenkirchen EW and Nabholz JV. 1989. Generic environmental hazard assessment of hydrazines and related compounds. Rockville, Maryland: Dynamac Corporation, 11140 Rockville Pike, 20852.

LIST OF HYDRAZINES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ HYDRAZINES USED IN CALCULATION OF THE SAR Hydrazine 2.81 1.37 H Hydrazine 3.4 1.37 ON Monomethyl hydrazine 3.26 1.06 ON Monomethyl hydrazine 2.58 1.06 ON 1,1 Dimethyl hydrazine 7.75 1.50 H 1,1 Dimethyl hydrazine 10.0 1.50 ON 1,1 Dimethyl hydrazine 26.5 1.50 ON Thiosemicarbazide 20.8 2.4 ON 1,2 Diphenyl hydrazine 0.27 2.97 B HYDRAZINES LESS TOXIC THAN PREDICTED Butanedioic acid mono (2,2' dimethylhydrazide) 423.0 0.619 ON Butanedioic acid mono (2,2' dimethylhydrazide) 149.0 0.619 ON HYDRAZINES NOT ACUTELY TOXIC AT SATURATION N Acetyl 1,2 diphenylhydrazine * (mp 164EC) 2.2 H ____________________________________________________________________________________ ____

H = Hammermeister et al (1990) ON = Odenkirchen and Nabholz (1989) B = Buccafusco et al (1981) HYDRAZINES 9/ 1993 161 SAR HYDRAZINES Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 1.2941  0.256 log Kow Statistics: N = 4; R 2 = 0.46 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for:

hydrazines hydrazones hydrazides thiohydrazides semicarbazides thiosemicarbazides semicarbazones thiosemicarbazones For hydrazines with missing fragment constants in CLOGP the following constants may be used:

1. missing fragment ( C(= S)): 0.24 2. missing fragment ( NC(= O) N N): 3.13 3. missing fragment (C= NNC(= O) N): 3.39 Limitations: Hydrazines which are significantly less toxic than predicted by this SAR are those hydrazines which have a carboxylic acid substitution:

butanedioic acid mono( 2,2' dimethylhydrazide).

If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: LeBlanc. 1980. Acute toxicity of priority pollutants to water flea (Daphnia magna). Bulletin of Environmental Contamination and Toxicology. 24: 684 691.

Hammermeister D, Kahl M, and Broderius S. 1990. EEB/ ERL Duluth interaction on various join projects. Duluth, MN: Environmental Research Laboratory Duluth, United States Environmental Protection Agency, 6201 Congdon Blvd., 55804, Unpublished memorandum to V. Nabolz. HYDRAZINES 9/ 1993 162 LIST OF HYDRAZINES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ HYDRAZINES USED IN CALCULATION OF THE SAR Hydrazine 0.280 1.37 H 1,1 Dimethyl hydrazine 68.2 1.50 H 1,2 Diphenyl hydrazine 4.1 2.97 L HYDRAZINES NOT ACUTELY TOXIC AT SATURATION N Acetyl 1,2 diphenylhydrazine * (mp 164EC) 2.2 H ____________________________________________________________________________________ ____

H = Hammermeister et al (1990) L = LeBlanc (1980) HYDRAZINES 9/ 1993 163 SAR HYDRAZINES Organism: Green Algae Duration: 144 h Endpoint: EC50 (Growth)

Equation: Log 144 h EC50 (mM/ L) = 5.1725  0.0999 Log Kow Statistics: N = 3; R 2 = 0.3 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for hydrazines. SAR equations for other subclasses of hydrazines, i. e., alkylsemicarbazides and arylsemicarbazides, may be found elsewhere in this volume.

Limitations: Hydrazines which are significantly less toxic than predicted by this SAR are those hydrazines which have a carboxylic acid substitution:

butanedioic acid mono( 2,2' dimethylhydrazide).

References: Odenkirchen EW and Nabholz JV. 1989. Generic environmental hazard assessment of hydrazines and related compounds. Rockville, Maryland: Dynamac Corporation, 11140 Rockville Pike, 20852.

LIST OF HYDRAZINES USED TO DEVELOP THE GREEN ALGAE 144 h EC50 SAR. ____________________________________________________________________________________ ____ 144 h EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 1,1 Dimethyl hydrazine 0.004100 1.50 ON Hydrazine 0.000041 1.37 ON ____________________________________________________________________________________ ____

ON = Odenkirchen and Nabholz (1989) HYDRAZINES 9/ 1993 164 HYDRAZINES, SEMICARBAZIDES, ALKYL SUBSTITUTED 9/ 1993 165 SAR HYDRAZINES, SEMICARBAZIDE, ALKYL SUBSTITUTED Organism: Green Algae Duration: 6 h Endpoint: EC50 (Growth)

Equation: (1) For log Kow less than 1.02:

Log 6 h EC50 (mM/ L) = 2.1  0.521 log Kow (2) For log Kow greater than 1.02:

Log 6 h EC50 (mM/ L) = 0.89 + 0.625 log Kow Statistics: (1) For log Kow less than 1.02: N = 6, R 2 = 0.75; (2) For log Kow greater than 1.02: N = 7, R 2 = 0.86 Maximum log Kow : 1.5 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for the following hydrazine classes with alkyl substitutions:

semicarbazides thiosemicarbazides semicarbazones thiosemicarbazones hydrazides thiohydrazides hydrazones SAR equations for aryl substituted semicarbazides and hydrazines may be found elsewhere in this volume.

For semicarbazides with missing fragment constants in CLOGP the following constants may be used:

1. missing fragment ( C(= S)): 0.24 2. missing fragment ( NC(= O) N N): 3.13 3. missing fragment (C= NNC(= O) N): 3.39.

Limitations: If the log Kow value is greater than 1.5, no effects expected at saturation.

References: Odenkirchen EW and Nabholz JV. 1989. Generic environmental hazard assessment of hydrazines and related compounds. Rockville, Maryland: Dynamac Corporation, 11140 Rockville Pike, 20852. HYDRAZINES, SEMICARBAZIDES, ALKYL SUBSTITUTED 9/ 1993 166 LIST OF ALKYL SUBSTITUTED SEMICARBAZIDES USED TO DEVELOP THE GREEN ALGAE 6 h EC50 SAR. ____________________________________________________________________________________ ____ 6 h EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 4 Methyl 9.9 2.25 ON 4 Allyl 3.8 1.74 ON 4 Ethyl 5.1 1.73 ON 4,4 Dimethyl 4.2 1.50 ON 4 Isopropyl 2.7 1.42 ON 4 n Propyl 2.5 1.20 ON 4 t Butyl 4.1 1.02 ON 4 Isobutyl 3.9 0.80 ON 4 Benzyl 12.8 0.69 ON 4 n Butyl 5.9 0.67 ON 4,4 Diethyl 6.1 0.44 ON 4 n Pentyl 12.6 0.14 ON 4 n Hexyl 38.2 0.39 ON ____________________________________________________________________________________ ____

ON = Odenkirchen and Nabholz (1989) HYDRAZINES, SEMICARBAZIDES, ARYL, ORTHO SUBSTITUTED 9/ 1993 167 SAR HYDRAZINES, SEMICARBAZIDES, ARYL, ORTHO SUBSTITUTED Organism: Green Algae Duration: 6 h Endpoint: EC50 (Growth)

Equation: Log 6 h EC50 (mM/ L) = 0.88  0.563 log Kow Statistics: N = 7; R 2 = 0.98 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for the following arylsemicarbazides with ortho substituents on the aryl group:

thiosemicarbazides semicarbazones thiosemicarbazones hydrazides thiohydrazides hydrazones SAR equations for arylsemicarbazides with meta and para substituents, alkylsemicarbazides, and hydrazines may be found elsewhere in this volume.

For semicarbazides with missing fragment constants in CLOGP the following constants may be used:

1. missing fragment ( C(= S)): 0.24 2. missing fragment ( NC(= O) N N): 3.13 3. missing fragment (C= NNC(= O) N): 3.39.

Limitations: Arylsemicarbazides which are significantly more toxic than predicted by this SAR are:

4( o hydroxyphenyl) semicarbazide, 30X excess toxicity.

If the log Kow is greater than 5.0, or if the compound is solid and the EC50 exceeds the water solubility, no effects expected at saturation.

References: Odenkirchen EW and Nabholz JV. 1989. Generic environmental hazard assessment of hydrazines and related compounds. Rockville, Maryland: Dynamac Corporation, 11140 Rockville Pike, 20852. HYDRAZINES, SEMICARBAZIDE, ARYL, ORTHO SUBSTITUTED 9/ 1993 168 LIST OF ARYLSEMICARBAZIDES WITH ORTHO SUBSTITUENTS ON THE ARYL GROUP USED TO DEVELOP THE GREEN ALGAE 6 h EC50 SAR. ____________________________________________________________________________________ ____ 6 h EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ ARYLSEMICARBAZIDES USED IN CALCULATION OF THE SAR 4[ o Nitrophenyl] 194.6 1.47 ON 4[ o Carboxyphenyl] 176.6 1.47 ON 4[ o Methoxyphenyl] 116.2 1.30 ON 4[ o Methylphenyl] 52.0 0.57 ON 4[ o Chlorophenyl] 39.4 0.50 ON 4[ m Bromophenyl] 26.2 0.35 ON 4[ o Bromophenyl] 53.4 0.35 ON 4[ 2,5 Dichlorophenyl] 22.3 0.21 ON ARYLSEMICARBAZIDES HAVING EXCESS TOXICITY 4[ o Hydroxyphenyl] 6.0 1.88 ON ____________________________________________________________________________________ ____

ON = Odenkirchen and Nabholz (1989) HYDRAZINES, SEMICARBAZIDE, ARYL, META/ PARA SUBSTITUTED 9/ 1993 169 SAR HYDRAZINES, SEMICARBAZIDES, ARYL, META/ PARA SUBSTITUTED Organism: Green Algae Duration: 6 h Endpoint: EC50 (Growth)

Equation: Log 6 h EC50 (mM/ L) = 1.13  0.461 log Kow Statistics: N = 19; R 2 = 0.98 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for the following arylsemicarbazides with meta or para substituents on the aryl group:

thiosemicarbazides semicarbazones thiosemicarbazones hydrazides thiohydrazides hydrazones For semicarbazides with missing fragment constants in CLOGP the following constants may be used:

1. missing fragment ( C(= S)): 0.24 2. missing fragment ( NC(= O) N N): 3.13 3. missing fragment (C= NNC(= O) N): 3.39.

Limitations: SAR equations for arylsemicarbazides with ortho substituents, alkylsemicarbazides, and hydrazines may be found elsewhere in this volume. If the log Kow value is greater than 8.0, or if the compound is solid and the EC50 exceeds the water solubility, no effects expected at saturation.

References: Odenkirchen EW and Nabholz JV. 1989. Generic environmental hazard assessment of hydrazines and related compounds. Rockville, Maryland: Dynamac Corporation, 11140 Rockville Pike, 20852. HYDRAZINES, SEMICARBAZIDE, ARYL, META/ PARA SUBSTITUTED 9/ 1993 170 LIST OF ARYLSEMICARBAZIDES WITH META AND PARA SUBSTITUENTS ON THE ARYL GROUP USED TO DEVELOP THE GREEN ALGAE 6 h EC50 SAR. ____________________________________________________________________________________ ____ 6 h EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 4[ m Hydroxyphenyl] 144.8 1.88 ON 4[ p Hydroxyphenyl] 170.0 1.88 ON 4[ m Nitrophenyl] 109.5 1.47 ON 4[ p Nitrophenyl] 98.0 1.47 ON 4[ m Carboxyphenyl] 104.0 1.47 ON 4[ p Carboxyphenyl] 92.7 1.47 ON 4[ m Methoxyphenyl] 71.7 1.30 ON 4[ p Methoxyphenyl] 70.0 1.30 ON 4 Phenyl 42.5 1.22 ON 4[ p Ethoxyphenyl] 38.7 0.77 ON 4[ m Methylphenyl] 26.7 0.57 ON 4[ p Methylphenyl] 24.9 0.57 ON 4[ m Chlorophenyl] 22.7 0.50 ON 4[ p Chlorophenyl] 22.2 0.50 ON 4[ m Bromophenyl] 26.2 0.35 ON 4[ p Bromophenyl] 22.3 0.35 ON 4[ p Iodophenyl] 17.7 0.09 ON 4[ 3,4 Dichlorophenyl] 9.3 0.21 ON 4[ 2,5 Dichlorophenyl] 22.3 0.21 ON ____________________________________________________________________________________ ____

ON = Odenkirchen and Nabholz (1989) IMIDES 9/ 1993 171 SAR IMIDES Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 1.256  0.76 log Kow Statistics: N = 4; R 2 = 0.98 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for imides.

Limitations: For imides with log Kow values greater than 5.0, a test duration of greater than 96 hours may be required for proper expression of toxicity. Also, if the toxicity value obtained by the use of this equation exceeds the water solubility of the compound (measured or estimated), mortalities greater than 50% would not be expected in a saturated solution during an exposure period of 96 hours.

References: Fukunaga K (ed). 1987. Japanese Pesticides Guide. Tokyo, Japan: Japan Plant Protection Association.

Worthing CR (ed). 1983. The Pesticide Manual. A World Compendium. 7th Ed. Croydon, Great Britain: British Crop Protection Council.

LIST OF IMIDES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Methylene chloride 322.895 1.25 Z Sumilex * 2.2 F Vinclozolin 32.5 2.8 W Vinclozolin 52.5 2.8 W Spartcide 5.5 3.7 F ____________________________________________________________________________________ ____

* = No fish mortality in saturated solutions. IMIDES 9/ 1993 172 F = Fukunaga (1987) W = Worthing (1983) KETONES, DI, ALIPHATIC 9/ 1993 173 SAR KETONES, DI, ALIPHATIC Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 0.151  0.433 log Kow Statistics: N = 22; R 2 = 0.87 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for aliphatic diketones.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: Brooke LT, Call DJ, Geiger DL, and Northcott CE. 1984. Acute toxicities of organic chemicals to fathead minnows (Pimephales promelas). Volume 1. Superior, WI: University of Wisconsin, Center for Lake Superior Environmental Studies. pp. 414.

Geiger DL, Northcott EC, Call DJ, and Brooke LT. 1985. Acute toxicities of organic chemicals to fathead minnows (Pimephales promelas). Volume 2. Superior, WI: University of Wisconsin, Center for Lake Superior Environmental Studies. pp. 326.

Juhnke I and Luedemann D. 1978. Results of the investigation of 200 chemical compounds for acute fish toxicity with the golden orfe test. Z. F. Wasser Und Abwasser Forschung 11( 5): 161 164.

Nacci D, et al. 1986. Comparative evaluation of three rapid marine toxicity tests: sea urchin early embryo growth test, sea urchin sperm cell toxicity test and microtox. Environmental Toxicology and Chemistry. 5: 521 525.

Phipps GL and Holcombe GW. 1985. A method for aquatic multiple species toxicant testing: Acute toxicity of 10 chemicals to 5 vertebrates and 2 invertebrates. Environ. Pollut. Ser. A Ecol. Biol. 38( 2): 141 157.

Thurston RV, Gilfoil TA, Meyn EL, Zajdel RK, Aoki, TL, and Veith GD. 1985. Comparative toxicity of ten organic chemicals to ten common aquatic species. Water Res. 19( 9): 1145 1155. United States Environmental Protection Agency (USEPA). 1991. Fish Chronic Toxicity Data Base. Duluth, MN: Environmental Research Laboratory (ERL), Office of Research and Development, USEPA, 6201 Congdon Boulevard, 55804; contact C. L. Russom (218) 720 5500. KETONES, DI, ALIPHATIC 9/ 1993 174 LIST OF ALIPHATIC DIKETONES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Methylene chloride 322.895 1.25 Z 2,4 pentanedione 116.0 0.5 J 2,4 pentanedione 104.0 0.5 N 5,5 dimethyl 1,3 11,500.0 0.5 EPA cyclohexanedione 2,4 pentanedione 175.0 0.5 G 1 benzoyl acetone 1.1 1.0 EPA 2,4 pentanedione 104.0 0.5 B 2,4 pentanedione 146.0 0.5 J 2,4 pentanedione 155.0 0.5 P 2,4 pentanedione 71.6 0.5 P 2,4 pentanedione 107.0 0.5 P 2,4 pentanedione 83.6 0.5 P 2,4 pentanedione 74.3 0.5 P 2,4 pentanedione 92.4 0.5 T 2,4 pentanedione 71.7 0.5 T 2,4 pentanedione 66.9 0.5 T 2,4 pentanedione 60.1 0.5 T 2,4 pentanedione 204.0 0.5 T 2,4 pentanedione 151.0 0.5 T 2,4 pentanedione 106.0 0.5 T 2,4 pentanedione 121.0 0.5 T 2,4 pentanedione 143.0 0.5 T 2,4 pentanedione 141.0 0.5 T ____________________________________________________________________________________ ____

B = Brooke et al (1984) EPA = USEPA (1991) G = Geiger et al (1985) J = Juhnke and Luedemann (1978) N = Nacci et al (1986) P = Phipps and Holcombe (1985) T = Thurston et al (1985) KETONES, DI, ALIPHATIC 9/ 1993 175 SAR KETONES, DI, ALIPHATIC Organism: Daphnid Duration: 48 h Endpoint: LC50 Equation: Log 48 h LC50 (mM/ L) = 0.466  0.467 log Kow Statistics: N = 6; R 2 = 0.98 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for aliphatic diketones.

Limitations: If the Kow value is greater than 5.0, a or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: Elnabarawy MT, Welter AN, and Robideau RR. 1986. Relative sensitivity of three daphnid species to selected organic and inorganic chemicals. Environ. Toxicol. Chem. 5( 4): 393 398.

Mount DI and Norberg TJ. 1984. A seven day life cycle cladoceran toxicity test. Environ. Toxicol. Chem. 3( 3): 425 434.

Nacci D, et al. 1986. Comparative evaluation of three rapid marine toxicity tests: sea urchin early embryo growth test, sea urchin sperm cell toxicity test and microtox. Environmental Toxicology and Chemistry. 5: 521 525.

LIST OF ALIPHATIC DIKETONES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Methylene chloride 322.895 1.25 Z 2,4 pentanedione 47.6 0.5 N 2,4 pentanedione 75.0 0.5 E 2,4 pentanedione 75.0 0.5 E 2,4 pentanedione 75.0 0.5 E 2,4 pentanedione 35.4 0.5 M ____________________________________________________________________________________ ____ KETONES, DI, ALIPHATIC 9/ 1993 176 E = Elnabarawy et al (1986) M = Mount and Norberg (1984) N = Nacci et al (1986) KETONES, DI, ALIPHATIC 9/ 1993 177 SAR KETONES, DI, ALIPHATIC Organism: Daphnid Duration: 16 d Endpoint: ChV Equation: Log ChV (mM/ L) = 1.841  0.482 log Kow Statistics: N = 4; R 2 = 0.98 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for aliphatic diketones.

Limitations: If the log Kow value is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

References: Elnabarawy MT, Welter AN, and Robideau RR. 1986. Relative sensitivity of three daphnid species to selected organic and inorganic chemicals. Environ. Toxicol. Chem. 5( 4): 393 398.

LIST OF ALIPHATIC DIKETONES USED TO DEVELOP THE DAPHNID ChV SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Methylene chloride 322.895 1.25 Z 2,4 pentanedione 6.5 0.5 E 2,4 pentanedione 2.6 0.5 E 2,4 pentanedione 1.0 0.5 E ____________________________________________________________________________________ ____

E = Elnabarawy et al. (1986) KETONES, DI, ALIPHATIC 9/ 1993 178 KETONES, DI, ALIPHATIC 9/ 1993 179 SAR KETONES, DI, ALIPHATIC Organism: Green Algae Duration: Endpoint: ChV Equation: Log ChV (mM/ L) = 1.806  0.412 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for aliphatic diketones.

Limitations: If the log Kow value is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

References: Bringmann G and Kuhn R. 1980. Comparison of the toxicity thresholds of water pollutants to bacteria, algae, and protozoa in the cell multiplication inhibition test. Water Res. 14( 3): 231 241.

LIST OF ALIPHATIC DIKETONES USED TO DEVELOP THE GREEN ALGAE ChV SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 2,4 pentanedione 2.7 0.5 BK ____________________________________________________________________________________ ____

BK = Bringmann and Kuhn (1980) KETONES, DI, ALIPHATIC 9/ 1993 180 MALONONITRILES 9/ 1993 181 SAR MALONONITRILES Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 2.079  0.139 log Kow Statistics: N = 3; R 2 = 0.40 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for malononitriles.

Limitations: For malononitriles with log Kow values greater than 5.0, a test duration of greater than 96 hours may be required for proper expression of toxicity. Also, if the acute toxicity value obtained by the use of this equation exceeds the water solubility of the compound (measured or estimated), significant mortalities would not be expected in a saturated solution during an exposure period of 96 hours.

References: Abram FSH and Wilson P. 1979. The acute toxicity of CS to rainbow trout. Water Research 13: 631 635.

LIST OF MALONONITRILES USED TO DEVELOP THE FISH 96 H LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Malononitrile 1.6 1.2 A o Chlorobenzylidene malononitrile 0.22 1.8 A ____________________________________________________________________________________ ____

A = Abram and Wilson (1979) MALONONITRILES 9/ 1993 182 NEUTRAL ORGANICS 7/ 1988 183 SAR NEUTRAL ORGANICS Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 1.75  0.94 log Kow Statistics: N = 60; R 2 = 0.942 Maximum Kow : 5.0 Maximum MW: 1000.0 Application: Solvents, non reactive, non ionizable neutral organic compounds 1. Alcohols 2. Acetals 3. Ketones 4. Ethers 5. Alkyl halides 6. Aryl halides 7. Aromatic hydrocarbons 8. Halogenated aromatic hydrocarbons 9. Halogenated aliphatic hydrocarbons 10. Sulfides and di sulfides Limitations: Use the fish 14 day LC50 for neutral organics with log Kow greater than 5 and less than 7. If the compound is and the LC50 is exceeds the water solubility, use SAR with longer exposure.

References: Veith GD, Call DJ, and Brooke LT. 1983. Structure toxicity relationships for the fathead minnow, Pimephales promelas: narcotic industrial chemicals. Canadian Journal of Fisheries and Aquatic Sciences 40: 743 748. NEUTRAL ORGANICS 7/ 1988 184 LIST OF NEUTRAL ORGANICS USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Triethylene glycol 69800 1.17 V 2 Methyl 2,4 pentandiol 10700 0.70 V Methanol 28100 0.66 V Acetone 8120 0.24 V Ethanol 14200 0.16 V 2( 2 Ethoxyethoxy) ethanol 26400 0.08 V 2 Propanol 10400 0.14 V 2 Butanone 3200 0.28 V 3 Furanmethanol (static) 508 0.32 V Tetrahydrofuran 2160 0.46 V 3 Methyl 2 butanone 864 0.62 V 2 Methyl 1 propanol 1430 0.74 V Cyclohexanone 527 0.81 V 3 Pentanone 1540 0.84 V 1 Butanol 1730 0.88 V 3,3 Dimethyl 2 butanone 87 0.94 V 2', 3', 4' Trimethoxyacetophenone 172 1.12 V 2 Phenoxyethanol 344 1.16 V Cyclohexanol 704 1.23 V 4 Methyl 2 pentanone 505 1.25 V t Butylmethyl ether 706 1.30 V Furan 61 1.34 V 2,2,2 Trichloroethanol 299 1.38 V Diisopropyl ether 91.7 1.56 V Acetophenone 162 1.66 V 5 Methyl 2 hexanone 159 1.79 V 1,3 Dichloroethane 118 1.79 V p Dimethoxybenzene 117 2.00 V 1 Fluoro 4 nitrobenzene 28.4 2.02 V 1 Hexanol 97.5 2.03 V 1,1,2 Trichloroethane 81.7 2.07 V 6 Methyl 5 heptene 2 one 85.7 2.13 V 2' Hydroxy 4' methoxyacetophenone 54.9 2.14 V 1,1,2,2 Tetrachloroethane 20.3 2.39 V 1,1,2 Trichloroethylene 44.1 2.42 V 2 Octanone 36 2.46 V Tetrachloroethane 13.5 2.53 V 2,6 Dimethoxytoluene 20.5 2.67 V 5 Nonanone 31 3.00 V 2', 4' Dichloroacetophenone 11.7 3.02 V 1 Octanol 13.5 3.03 V Di n butyl ether 32.5 3.08 V ____________________________________________________________________________________ ____ NEUTRAL ORGANICS 7/ 1988 185 Continued. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 1,4 Dichlorobenzene 4.0 3.37 V Benzophenone 15.3 3.38 V 1,3 Dichlorobenzene 7.8 3.38 V 1 Nonanol 5.7 3.53 V 2 Decanone 5.7 3.54 V Pentachloroethane 7.3 3.64 V 2', 3', 4' Trichloroacetophenone 2.0 3.73 V p Nitrophenyl phenyl ether 2.7 3.97 V 1 Decanol 2.4 4.03 V Dipentyl ether 3.2 4.16 V 3,4 Dichlorotoluene 2.91 4.22 V á, á 2,6 Tetrachlorotoluene 0.97 4.24 V Diphenyl ether 4.0 4.26 V 1,2,4 Trichlorobenzene 2.9 4.28 V 1 Undecanol 1.04 4.53 V Hexachloroethane 1.5 4.62 V 1 Dodecanol 1.01 5.00 V 7 Tridecanone * 5.16 V 1 Tridecanol * 5.51 V Pentachlorobenzene * 5.71 V 1,2,3,4 Tetrachlorobenzene 1.1 5.71 V Hexachlorobenzene * 5.71 V Dioctyl ether * 6.42 V ____________________________________________________________________________________ ____

* = No fish mortality in saturated solutions.

V = Veith et al. (1983) NEUTRAL ORGANICS 7/ 1988 186 NEUTRAL ORGANICS 7/ 1988 187 SAR NEUTRAL ORGANICS Organism: Fish, Sheepshead Minnow (marine) Duration: 96 h Endpoint: LC50 (Mortality)

Endpoint: Log LC50 (mM/ L) = 0.69  0.73 log Kow Statistics: N = 37; R 2 = 0.656 Maximum Kow : 5.0 Maximum MW: 1000.0 Application: Solvents, non reactive, non ionizable neutral organic compounds:

1. Alcohols 2. Acetals 3. Ketones 4. Ethers 5. Alkyl halides 6. Aryl halides 7. Aromatic hydrocarbons 8. Halogenated aromatic hydrocarbons 9. Halogenated aliphatic hydrocarbons 10. Sulfides and di sulfides Limitations: If the log Kow is greater than 5, or if the compound is solid and the LC50 is exceeds the water solubility, use SAR with longer exposure.

References: Zaroogian G, Heltshe JF, and Johnson M. 1985. Estimation of toxicity to marine species with structure activity models developed to estimate toxicity to freshwater fish. Aquatic Toxicology 6: 251 270. NEUTRAL ORGANICS 7/ 1988 188 LIST OF NEUTRAL ORGANICS USED TO DEVELOP THE SHEEPSHEAD MINNOW 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Methylene chloride 322.895 1.25 Z Diethyl phthalate 29.979 1.40 Z 1,1 Dichloroethylene 249.174 1.48 Z 2,4 Dinitrophenol 28.515 1.53 Z Dimethyl phthalate 57.310 1.61 Z Nitrobenzene 58.924 1.83 Z 1,1,1,2,2,2, Hexachloroethane 1.380 1.91 Z 4 Nitrophenol 26.507 1.91 Z 1,3 Dichloropropene 1.759 1.98 Z 2,3 Dinitrotoluene 2.293 1.98 Z 2,4,6 Trinitrophenol 128.838 2.03 Z Bromoform 17.893 2.30 Z 4 Chlorophenol 5.359 2.35 Z 1,1,2,2 Tetrachloroethane 11.883 2.39 Z 1,1,1 Trichloroethane 70.015 2.47 Z 1,1,1,2,2 Pentachloroethane 113.762 2.89 Z Diazinon 1.457 3.14 Z 1,4 Dichlorobenzene 7.200 3.38 Z 1,2 Dichlorobenzene 9.491 3.40 Z 1,3 Dichlorobenzene 7.715 3.44 Z 2,4,5 Trichlorophenol 1.681 3.72 Z Hexachlorobutadiene 0.545 3.74 Z Chlorobenzene 9.804 3.79 Z Disulfoton 0.739 3.81 Z Lindane 0.801 3.89 Z Dibenzofuran 1.761 4.10 Z Diphenyl ether 2.350 4.21 Z Dieldrin 0.010 4.31 Z 1,2,4 Trichlorobenzene 20.833 4.32 Z 1,2,3,5 Tetrachlorobenzene 3.666 4.46 Z 1,2,4,5 Tetrachlorobenzene 0.784 4.67 Z Methoxychlor 0.049 4.68 Z Chloropyrifos 0.881 4.82 Z Heptachlor 0.004 5.44 Z Kepone 0.693 6.08 Z Fenvalerate 0.004 6.20 Z Parmethrin 0.068 6.50 Z ____________________________________________________________________________________ ____

Z = Zaroogian et al. (1985) NEUTRAL ORGANICS 7/ 1988 189 SAR NEUTRAL ORGANICS Organism: Fish Duration: 14 day Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 1.87  0.871 log Kow Statistics: N = 50; R 2 = 0.976 Maximum Kow : 8.0 Maximum MW: 1000.0 Application: Solvents, non reactive, non ionizable neutral organic compounds:

1. Aromatic hydrocarbons 2. Halogenated aromatic hydrocarbons 3. Halogenated aliphatic hydrocarbons 4. Alcohols 5. Ketones 6. Acetals 7. Ethers 8. Alkyl halides 9. Aryl halides 10. Sulfides and di sulfides Also applicable to reactive compounds (i. e., compounds which show excess toxicity) whose log Kow is greater than 5.0, such as:

1. Esters 2. Acrylates 3. Methacrylates 4. Substituted benzotriazoles Limitations: If the log Kow is greater than 8.0, or if the compound is solid and the LC50 exceeds the water solubility, use SAR with longer exposure.

References: Konemann H. 1981. Quantitative structure activity relationships in fish toxicity studies. Part 1: Relationship for 50 industrial pollutants. Toxicology 19( 3): 209 221. NEUTRAL ORGANICS 7/ 1988 190 LIST OF NEUTRAL ORGANICS USED TO DEVELOP THE FISH 14 d LC50 SAR. ____________________________________________________________________________________ ____ 14 d LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Ethanediol (ethyleneglycol) 49303.00 1.35 K Digol (diethyleneglycol) 61065.00 1.30 K Trigol (triethyleneglycol) 62601.00 1.24 K 2 Methoxyethanol 17433.00 0.74 K Acetone 6368.00 0.30 K Ethanol 11051.00 0.26 K 2 Ethoxyethanol 16399.00 0.21 K Propanol 2 7061.00 0.15 K 2 Isopropoxyethanol 5467.00 0.20 K 2 Methylpropanol 2 3547.00 0.77 K 2 Butoxyethanol 983.00 0.86 K Diethylether 2137.00 0.88 K Butyldigol 1148.00 0.91 K Butyltrigol 197.00 0.97 K Pentanol 3 989.00 1.21 K Dichloromethane 294.00 1.61 K 1,3 Dichloropropane 83.80 1.71 K 1,2 Dichloroethane 106.00 1.76 K 2,2' Dichlorodiethylether 54.40 1.81 K 1,1 Dichloroethane 202.00 1.92 K Chloroform 102.00 2.02 K Trans 1,4 dichloro 2 butene 39.50 2.11 K Benzene 63.50 2.13 K 1,2 Dichloropropane 115.00 2.16 K Trichloroethane 55.60 2.20 K 1 Chlorobutane 96.90 2.35 K 1,1,2 Trichloroethane 94.40 2.38 K 2,4 Dichloroaniline 11.70 2.42 K 1,1,1 Trichloroethane 133.00 2.49 K Toluene 68.30 2.59 K 2,3 Dichloro 1 propane 11.10 2.60 K 1,2,3 Trichloropropane 41.60 2.63 K 1,5 Dichloropentane 11.20 2.77 K Tetrachloromethane 67.10 2.79 K Monochlorobenzene 19.10 2.81 K á, á' Dichloro m xylene 0.12 2.87 K Tetrachloroethane 18.00 2.95 K 1,1,2,2 Tetrachloroethane 36.70 3.01 K o Xylene 35.20 3.09 K m Xylene 37.70 3.09 K p Xylene 35.20 3.09 K Cyclohexane 84.20 3.18 K ____________________________________________________________________________________ ____ NEUTRAL ORGANICS 7/ 1988 191 Continued. ____________________________________________________________________________________ ____ 14 d LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 4 Chlorotoluene 5.90 3.31 K 3 Chlorotoluene 18.30 3.31 K 1,2 Dichlorobenzene 5.80 3.53 K 1,3 Dichlorobenzene 7.40 3.53 K 1,4 Dichlorobenzene 4.00 3.53 K Pentachloroethane 15.00 3.58 K 2,4,á Trichlorotoluene 0.24 3.87 K 2,4 Dichlorotoluene 4.60 3.98 K 3,4 Dichlorotoluene 5.10 3.98 K 1,2,3 Trichlorobenzene 2.30 4.20 K 1,2,4 Trichlorobenzene 2.40 4.20 K 1,3,5 Trichlorobenzene 3.30 4.20 K Hexachlorobutadiene 0.39 4.63 K 2,4,5 Trichlorotoluene 1.70 4.72 K 1,2,4,5 Tetrachlorobenzene 0.30 4.94 K 1,2,3,5 Tetrachlorobenzene 0.80 4.94 K 1,2,3,4 Tetrachlorobenzene 0.80 4.94 K Pentachlorobenzene 0.18 5.69 K Hexachlorobenzene 0.32 6.44 K ____________________________________________________________________________________ ____

K = Konemann (1981) NEUTRAL ORGANICS 7/ 1988 192 NEUTRAL ORGANICS 7/ 1988 193 SAR NEUTRAL ORGANICS Organism: Fish Duration: > 30 days Endpoint: Chronic Value (Survival/ Growth; Early Life Stage)

Equation: Log ChV (mM/ L) = 0.72  0.87 log Kow Statistics: N = 20; R 2 = 0.91 Maximum Kow : 7.9 Maximum MW: 1000.0 Application: Solvents, non reactive, non ionizable neutral organic compounds:

1. Alcohols 2. Acetals 3. Ketones 4. Ethers 5. Alkyl halides 6. Aryl halides 7. Aromatic hydrocarbons 8. Halogenated aromatic hydrocarbons 9. Halogenated aliphatic hydrocarbons 10. Sulfides and di sulfides Limitations: If the log Kow is greater than 7.9 or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

References: United States Environmental Protection Agency (USEPA). 1991. Fish chronic toxicity data base. Duluth, MN: Environmental Research Laboratory (ERL), Office of Research and Development, USEPA, 6201 Congdon Blvd., 55804; contact C. L. Russom (218) 720 5500. NEUTRAL ORGANICS 7/ 1988 194 NEUTRAL ORGANICS 7/ 1988 195 SAR NEUTRAL ORGANICS Organism: Fish, Fathead minnow Duration: 28 d Endpoint: BCF (Bioconcentration Factor)

Equation: Log BCF = 0.79 log Kow  0.40 (the BCF is without units)

Statistics: N = 122; R2 = 0.927 Maximum Kow : 8.0 Maximum MW: 1000.0 Application: Solvents, non reactive, non ionizable compounds:

1. Aromatic amines 2. Acetals 3. Cyclodiene 4. Ethers 5. Halogenated alkyl 6. Halogenated aromatic 7. Halogenated indoles 8. Halogenated phenols 9. Phosphate esters Limitations: If log Kow is greater than 8.0, no significant BCF unless analog data can be found, e. g., PCBs.

Reference: Veith, GD, and Kosian, P. 1982. Estimating bioconcentration potential from octanol/ water partition coefficients. IN: Physical Behavior of PCB's in the Great Lakes. MacKay, Paterson, Eisenreich, and Simmons, eds. Ann Arbor, MI: Ann Arbor Science. NEUTRAL ORGANICS 7/ 1988 196 LIST OF CHEMICALS USED TO DEVELOP THE FISH BIOCONCENTRATION SAR. ____________________________________________________________________________________ ____ Log Log Ref. CHEMICAL BCF Kow ____________________________________________________________________________________ ____ Lindane 2.67 3.85 VK Atrazine 0.90 2.63 VK Heptachlor 4.30 5.44 VK 2 Ethylhexiphthalate 2.93 4.20 VK DASC 3 0.32 1.00 VK DASC 4 0.32 1.00 VK NTS 1 0.66 1.00 VK BSB 0.32 1.00 VK FWA 2 A 0.32 1.80 VK FWA 3 A 0.32 1.48 VK FWA 4 A 0.32 1.20 VK Nitrobenzene 1.18 2.93 VK p Nitrophenol 1.88 1.91 VK Naphthalene 2.63 3.59 VK Chlorobenzene 2.65 3.79 VK 2,4,5 Trichlorophenol 3.28 3.72 VK Endrin 3.66 4.56 VK 1,1,2,2 Tetrachloroethylene 2.06 2.88 VK Hexachlorobenzene 4.37 6.18 VK p Biphenylphenyl ether 3.22 5.55 VK Carbon tetrachloride 2.77 4.21 VK p Dichlorobenzene 1.72 2.64 VK Biphenyl 2.81 3.38 VK Chloropyrifos 2.67 4.82 VK Endrin 3.17 4.56 VK 2,5,6 Trichloropyridinol 0.49 1.35 VK Fluorene 3.11 4.38 VK Dibenzofuran 3.13 4.12 VK 2 Chlorophenanthrene 3.63 5.16 VK Phenanthrene 3.42 4.46 VK 2 Methylphenanthrene 3.48 4.86 VK Heptachlor 3.98 5.44 VK Heptachloroepoxide 4.16 5.40 VK p, p' DDE 4.71 5.69 VK Pentachlorophenol 2.89 2.97 VK Hexabromobiphenyl 6.39 4.26 VK Methoxychlor 3.92 4.30 VK Mirex 4.26 6.89 VK Hexabromocyclododecane 4.26 5.81 VK Heptachloronorborene 4.05 5.28 VK Hexachloronorbornadiene 3.81 5.28 VK 1,2 Dichlorobenzene 1.95 3.40 VK 1,3 Dichlorobenzene 1.82 3.44 VK NEUTRAL ORGANICS 7/ 1988 197 Continued. ____________________________________________________________________________________ ____ Log Log Ref. CHEMICAL BCF Kow ____________________________________________________________________________________ ____ 1,4 Dichlorobenzene 1.78 3.37 VK 1,2,3,5 Tetrachlorobenzene 3.26 4.46 VK Pentachlorobenzene 3.53 4.94 VK Carbon tetrachloride 1.48 2.73 VK Chloroform 0.78 1.90 VK 1,2 Dichloroethane 0.30 1.45 VK 1,1,1 Trichloroethane 0.95 2.47 VK 1,1,2,2 Tetrachloroethane 0.90 2.39 VK Pentachloroethane 1.83 3.21 VK Hexachloroethane 2.14 3.93 VK Bis( 2 chloroethyl) ether 1.04 1.12 VK 1,1,2 Trichloroethylene 1.23 2.42 VK Tetrachloroethylene 1.69 2.53 VK Isophorone 0.84 1.67 VK N Nitrosophenylamine 2.34 3.13 VK 2 Chlorophenol 2.33 2.16 VK 2,4 Dimethylphenol 2.33 2.16 VK Butylbenylphthalate 2.89 4.05 VK Dimethylphthalate 1.76 1.61 VK Alkyl benzene sulfonate 2.02 1.59 VK Alkyl benzene sulfonate 1.56 1.59 VK Naphthalene 1.90 3.59 VK 2 Methylnaphthalene 2.28 3.84 VK 1 Methylnaphthalene 2.11 3.84 VK Hexachlorocyclohexane 2.15 3.85 VK Hexachlorocyclohexane 2.70 3.85 VK Endrin 4.02 4.56 VK Endrin 4.18 4.56 VK Endrin 3.85 4.56 VK Al254 4.60 6.47 VK Al254 4.43 6.47 VK 1,4 Dichlorobenzene 1.96 3.37 VK 1,2,3 Trichlorobenzene 2.81 4.20 VK 1,3,5 Trichlorobenzene 2.85 4.20 VK 1,2,3,5 Tetrachlorobenzene 3.56 4.46 VK Pentachlorobenzene 4.11 4.94 VK Hexachlorobenzene 4.16 6.18 VK Aroclor 1016 4.63 5.86 VK Aroclor 1248 4.85 6.11 VK Aroclor 1254 5.00 6.47 VK Aroclor 1260 5.29 6.91 VK Chlordane 4.58 6.00 VK Octachlorostyrene 4.52 6.29 VK p, p DDT 4.47 5.75 VK Continued. NEUTRAL ORGANICS 7/ 1988 198 ____________________________________________________________________________________ ____ Log Log Ref. CHEMICAL BCF Kow ____________________________________________________________________________________ ____ o, p DDT 4.57 5.75 VK Hexachlorobenzene 4.27 6.18 VK 1,2,4 Trichlorobenzene 3.32 4.23 VK Lindane 2.26 3.85 VK 5 Bromoindole 1.15 2.97 VK 2,4,6 Tribromoanisol 2.94 4.48 VK N Phenyl 2 naphylamine 2.17 4.38 VK Tricresyl phosphate 2.22 3.42 VK Diphenyl amine 1.48 3.42 VK Toluene 1.96 3.16 VK 1,1,2,2 Tetrachloroethylene 0.91 2.39 VK Pentachloroethane 1.78 3.21 VK Hexachloroethane 2.85 3.93 VK 1,3 Dichlorobenzene 1.99 3.44 VK 1,4 Dichlorobenzene 2.05 3.37 VK 1,2,4 Trichlorobenzene 2.60 4.52 VK 1,2,3,4 Tetrachlorobenzene 3.41 4.46 VK Hexachlorobenzene 4.37 6.18 VK Hexachloro 1,3 butadiene 3.84 5.10 VK Acridine 2.10 3.30 VK Toxaphene 3.64 5.28 VK Toxaphene 3.59 5.28 VK Pentachlorophenol 1.11 2.97 VK Imidan 0.90 2.83 VK Imidan 1.04 2.83 VK Imidan 0.90 2.83 VK Diazinon 1.56 1.92 VK Diazinon 1.81 1.92 VK Diazinon 1.24 1.92 VK Endrin 3.21 4.56 VK Acenaphthene 2.59 3.92 VK ____________________________________________________________________________________ ____ VK = Veith and Kosian (1982) NEUTRAL ORGANICS 7/ 1988 199 SAR NEUTRAL ORGANICS Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 1.72  0.91 log Kow Statistics: N = 19; R 2 = 0.992 Maximum Kow : 5.0 Maximum MW: 1000.0 Application: Solvents, non reactive, non ionizable compounds:

1. Aromatic hydrocarbons 2. Halogenated aromatic hydrocarbons 3. Halogenated aliphatic hydrocarbons 4. Alcohols 5. Ketones 6. Acetals 7. Ethers 8. Alkyl halides 9. Aryl halides 10. Sulfides and di sulfides Also be applied to some classes of reactive organic compounds which show excess toxicity to fish, such as:

1. Benzotriazoles 2. Phthalate esters 3. Esters LIMITATIONS: If the log Kow is greater than 5.0 and less than 8.0, or if the compound is solid and the LC50 exceeds the water solubility, use SAR with longer exposure.

References: Hermans J, Canton H, Janssen P, and De Jong R. 1984. Quantitative structureactivity relationships and toxicity studies of mixtures of chemicals with anaesthetic potency: Acute lethal and sublethal toxicity to Daphnia magna. Aquatic Toxicology 5: 143 154. NEUTRAL ORGANICS 7/ 1988 200 LIST OF NEUTRAL ORGANICS USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Ethanediol 50452 1.35 H Acetone 6081 0.30 H Ethanol 5413 0.26 H 2 Ethoxyethanol 7670 0.21 H Diethylether 1380 0.88 H Benzene 56.6 2.13 H 1,2 Dichloropropane 45.0 2.16 H 1,1,2 Trichloroethene 20.8 2.20 H Toluene 14.9 2.59 H 1,2,3 Trichloropropane 35.4 2.63 H Monochlorobenzene 25.8 2.81 H m Xylene 14.3 3.09 H 4 Chlorotoluene 3.6 3.31 H 1,2 Dichlorobenzene 3.8 3.53 H 2,4 Dichlorotoluene 0.62 3.98 H 1,2,4 Trichlorobenzene 2.7 4.20 H 2,4,5 Trichlorobenzene 0.55 4.72 H 1,2,3,4 Tetrachlorobenzene 0.54 4.94 H Pentachlorobenzene 0.12 5.69 H ____________________________________________________________________________________ ____

H = Hermans et al. (1984) NEUTRAL ORGANICS 7/ 1988 201 SAR NEUTRAL ORGANICS Organism: Mysid shrimp Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 1.83  1.25 log Kow Statistics: N = 17; R 2 = 0.706 Maximum Kow : 5.0 Maximum MW: 1000.0 Application: Solvents, non reactive, non ionizable compounds:

1. Alcohols 2. Acetals 3. Ketones 4. Ethers 5. Alkyl halides 6. Aryl halides 7. Aromatic hydrocarbons 8. Halogenated aromatic hydrocarbons 9. Halogenated aliphatic hydrocarbons 10. Sulfides and di sulfides Limitations: If the log Kow is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, use SAR with longer exposure.

References: Zaroogian G, Heltshe JF, and Johnson M. 1985. Estimation of toxicity to marine species with structure activity models developed to estimate toxicity to freshwater fish. Aquatic Toxicology 6: 251 270. NEUTRAL ORGANICS 7/ 1988 202 LIST OF NEUTRAL ORGANICS USED TO DEVELOP THE MYSID SHRIMP 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Toluene 55.5198 2.21 Z 1,3 Dichloropropane 10.0702 2.28 Z Tetrachloroethylene 9.9922 2.60 Z Benthiocarb 0.3235 3.40 Z Hexachlorobutadiene 0.0611 3.74 Z Chlorobenzene 16.2699 3.79 Z EPN 0.0032 3.85 Z Lindane 0.0059 3.89 Z Dieldrin 0.0050 4.31 Z 1,2,4 Trichlorobenzene 0.4454 4.32 Z 1,2,3,5 Tetrachlorobenzene 0.3344 4.46 Z Acenaphthene 0.0250 4.49 Z 1,2,4,5 Tetrachlorobenzene 1.4596 4.67 Z Pentachlorobenzene 0.1616 4.94 Z Heptachlor 0.0030 5.44 Z Leptophos 0.0033 6.08 Z Fenvalerate 0.0001 6.20 Z ____________________________________________________________________________________ ____

Z = Zaroogian et al. (1985) NEUTRAL ORGANICS 7/ 1988 203 SAR NEUTRAL ORGANICS Organism: Daphnid Duration: 16 d Endpoint: Chronic Value (EC50 Reproduction)

Equation: Log ChV (mM/ L) = 0.72 log Kow + 0.05 Statistics: N = 5; R 2 = 0.990 Maximum Kow : 8.0 Maximum MW: 1000.0 Application: Solvents, non reactive, non ionizable compounds:

1. Aromatic hydrocarbons 2. Halogenated aromatic hydrocarbons 3. Halogenated aliphatic hydrocarbons 4. Alcohols 5. Ketones 6. Acetals 7. Ethers 8. Alkyl halides 9. Aryl halides 10. Sulfides and di sulfides This SAR can also be applied to some classes of reactive organic compounds which show excess toxicity to fish, such as:

1. Benzotriazoles 2. Phthalate esters 3. Esters Limitations: If the log Kow is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

References: Hermans J, Canton H, Janssen P, and De Jong R. 1984. Quantitative structureactivity relationships and toxicity studies of mixtures of chemicals with anaesthetic potency: Acute lethal and sublethal toxicity to Daphnia magna. Aquatic Toxicology 5: 143 154. NEUTRAL ORGANICS 7/ 1988 204 LIST OF NEUTRAL ORGANICS USED TO DEVELOP THE DAPHNID 16 d EC50 SAR. ____________________________________________________________________________________ ____ 16 d EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Monochlorobenzene 25.8 2.81 H 4 Chlorotoluene 3.6 3.31 H 1,2,4 Trichlorobenzene 2.7 4.20 H 1,2,3,4 Tetrachlorobenzene 0.54 4.94 H Pentachlorobenzene 0.23 5.96 H ____________________________________________________________________________________ ____

H = Hermans et al. (1984) NEUTRAL ORGANICS 7/ 1988 205 SAR NEUTRAL ORGANICS Organism: Green algae Duration: 96 h Endpoint: EC50 (Growth)

Equation: Log 96 h EC50 (mM/ L) = 1.466  0.885 log Kow Statistics: N = 7; R 2 = 0.91 Maximum Kow : 6.4 Maximum MW: 1000.0 Application:

Limitations: If the log Kow is greater than 6.4, or if the compound is solid and the EC50 exceeds the water solubility, use SAR with longer exposure.

References: Calamari D, Galassi S, Setti F, and Vighi M. 1983. Toxicity of selected chlorobenzenes to aquatic organisms. Chemosphere 12: 253 262.

Galassi S and Vighi M. 1981. Testing toxicity of volatile substances with algae. Chemosphere 10: 1123 1126.

United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: USEPA, Office of Toxic Substances.

United States Environmental Protection Agency (USEPA). 1992. Aquatic toxicity database. Duluth, MN: USEPA, ERL  Duluth. NEUTRAL ORGANICS 7/ 1988 206 LIST OF NEUTRAL ORGANICS USED TO DEVELOP THE GREEN ALGAE 96 h EC50 SAR. ____________________________________________________________________________________ ____ 96 h EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Polyether 315 1.9 EPA Benzene 29 2.1 G Isolinalool 14 2.4 EPA Toluene 12.5 2.8 G Chlorobenzene 12.5 2.9 C trans Anethole 4.24 3.3 D Ethylbenzene 4.6 3.3 G o Xylene 4.7 3.4 G m Xylene 4.9 3.4 G p Xylene 3.2 3.4 G 1,2 Dichlorobenzene 2.2 3.6 C 1,4 Dichlorobenzene 0.57 3.6 C Isopropylbenzene 2.6 3.7 G n Propylbenzene 1.8 3.8 G 1,2,3 Trichlrorbenzene 0.22 4.3 C 1,2,4 Trichlorobenzene 0.37 4.3 C Hexachlorobenzene * 6.4 C ____________________________________________________________________________________ ____

* = No effects in saturated solutions.

C = Calamari et al. (1983) D = USEPA (1992). EPA = USEPA (1991); chemical identity is Confidential Business Information under TSCA G = Galassi and Vighi (1988) NEUTRAL ORGANICS 7/ 1988 207 SAR NEUTRAL ORGANICS Organism: Green algae Duration: Endpoint: Chronic Value (Growth)

Equation: Log ChV (mM/ L) = 0.036  0.634 log Kow Statistics: N = 7; R 2 = 0.99 Maximum Kow : 8.0 Maximum MW: 1000.0 Applications: May be applied to other neutral organics including aldehydes.

Limitations: If the log Kow is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

References: Calamari D, Galassi S, Setti F, and Vighi M. 1983. Toxicity of selected chlorobenzenes to aquatic organisms. Chemosphere 12: 253 262.

Galassi S and Vighi M. 1981. Testing toxicity of volatile substances with algae. Chemosphere 10: 1123 1126.

United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: USEPA, Office of Toxic Substances.

United States Environmental Protection Agency (USEPA). 1992. Aquatic toxicity database. Duluth, MN: USEPA, ERL  Duluth.

LIST OF NEUTRAL ORGANICS USED TO DEVELOP THE GREEN ALGAE ChV SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Polyether 15.9 1.9 EPA Isolinalool 4.8 2.4 EPA trans Anethole 3.09 3.3 D 1,4 Dichlorobenzene 0.57 3.6 C 1,2,3 Trichlrorbenzene 0.22 4.3 C 1,2,4 Trichlorobenzene 0.37 4.3 C Hexachlorobenzene 0.027 6.4 C NEUTRAL ORGANICS 7/ 1988 208 ____________________________________________________________________________________ ____

C = Calamari et al. (1983) D = USEPA (1992) EPA = USEPA (1991) NEUTRAL ORGANICS 7/ 1988 209 SAR NEUTRAL ORGANICS Organism: Earthworm Duration: 14 d Endpoint: LC50 (Mortality)

Equation: Log 14 d LC50 (mM/ L) = 1.405  0.308 log Kow Statistics: N = 5; R 2 = 0.48 Maximum Kow : 5.0 Maximum MW: 1000.0 Applications: Neutral organics Limitations: None References: Neuhauser EF, Durkin PR, Malecki MR, and Anatra M. 1986. Comparative toxicity of ten organic chemicals to four earthworm species. Comp. Biochem. Physiol. 83C: 197 200.

Neuhauser EF, Loehr RC, Malecki MR, Milligan DL, and Durkin PR. 1985. The toxicity of selected organic chemicals to the earthworm Eisenia fetida. Journal of Environmental Quality 14: 383 388.

LIST OF NEUTRAL ORGANIC CHEMICALS USED TO DEVELOP THE EARTHWORM 14 d LC50 SAR. ____________________________________________________________________________________ ____ 14 d LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 2 chloroethylvinylether 740.0 1.0 N nitrobenzene 319.0 1.9 N 1,2 dichloropropane 4240.0 2.0 N fluorene 173.0 4.2 N 1,2,4 trichlorobenzene 197.0 4.3 N ____________________________________________________________________________________ ____

N = Neuhauser et al. (1985, 1986) NEUTRAL ORGANICS 7/ 1988 210 PEROXY ACIDS 9/ 1993 211 SAR PEROXY ACIDS Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: log 96 h LC50 (mM/ L) = 2.6 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for peroxy acids.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, use SAR with longer exposure.

References: United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, USEPA.

LIST OF PEROXY ACIDS USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Chemical identity CBI 0.750 2.6 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991); chemical identity is Confidential Business Information under TSCA. PEROXY ACIDS 9/ 1993 212 PEROXY ACIDS 9/ 1993 213 SAR PEROXY ACIDS Organism: Daphnids Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 0.717 0.417 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for peroxy acids.

Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility, use SAR with longer exposure.

References: United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, USEPA.

LIST OF PEROXY ACIDS USED TO DEVELOP THE DAPHNID 48 H SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Chemical identity CBI 4.6 2.6 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991); chemical identity is Confidential Business Information under TSCA. PEROXY ACIDS 9/ 1993 214 PHENOLS 9/ 1993 215 SAR PHENOLS Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 0.399  0.616 log Kow Statistics: N = 78; R 2 = 0.86 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for phenols.

Limitations: Phenols which are significantly more toxic than predicted by this SAR are:

catechol with 16 x excess toxicity; hydroquinone with 1400 x excess toxicity; and p benzoquinone with 5500 x excess toxicity.

If the log Kow value is greater than 7.0, or if the compound is solid and the LC50 exceeds the water solubility, use SAR with longer exposure.

References: Alexander HC, Dill, DC, Smith LW, Guiney PD, and Dorn P. 1988. Bisphenol A: Acute aquatic toxicity. Environ. Toxicol. Chem. 7: 19 26.

Curtis MW and Ward CH. 1981. Aquatic toxicity of forty industrial chemicals: Testing in support of hazardous substance spill prevention regulation. Journal of Hydrology 51: 359 367.

DeGraeve GM, Geiger DL, Meyer JS, Bergman HL. 1980. Acute and embryo larval toxicity of phenolic compounds to aquatic biota. Arch. Environ. Contam. Toxicol. 9: 557 568.

Holcombe GW, Phipps GL, Knuth M, and Felhaber T. 1984. The acute toxicity of selected substituted phenols, benzenes, and benzioic acid esters to fathead minnows, Pimephales promelas. Environ. Pollution, Ser. A, 35: 367 381.

Holcombe GW, Phipps GL, and Fiandt JT. 1982. Effects of phenol, 2,4 dimethylphenol, 2,4 dichlorophenol, and pentachlorophenol on embryo, larval, and early juvenile fathead minnows (Pimephales promelas). Arch. Environ. Contam. Toxicol. 11: 73 78.

Konemann H, and Musch A. 1981. Quantitative structure activity relationships in fish toxicity studies. Part 2: The influence of pH on the SAR of chlorophenols. Toxicology 19: 223 228. PHENOLS 9/ 1993 216 Marking LL, Howe GE, and Bills TD. 1991. Temperature and pH effects on acute and chronic toxicity of four chemicals to amphipods (Gammarus pseudolimnaeus) and rainbow trout (Oncorhynchus mykiss). EPA/ 600/ X 90/ 286. Gulf Breeze, FL: Environmental Research Laboratory, Office of Research and Development, United States Environmental Protection Agency. August.

Saarikoski J and Viluksela M. 1982. Relation between physicochemical properties of phenols and their toxicity and accumulation in fish. Ecotoxicology and Environmental Safety 6: 501 512.

United States Environmental Protection Agency (USEPA1). 1980. Ambient Water Quality Criteria for Phenol. EPA 440 5 80 066. Washington, DC: Criteria and Standards Division, Office of Water Regulations and Standards, USEPA.

United States Environmental Protection Agency (USEPA2). 1984. Dynamic 14 day acute toxicity of octylphenol to rainbow trout (Salmo gairdneri). TSCA Section 4( d). Document No. 40 8462075. Washington, DC: OTS Public Files, USEPA. Fiche No. 0507489 (2).

United States Environmental Protection Agency (USEPA3). 1990. Section 8( e) 908.

United States Environmental Protection Agency (USEPA4). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, USEPA.

Veith GD and Broderius SJ. 1987. Structure toxicity relationships for industrial chemicals causing type (II) narcosis syndrome. IN: Kaiser KLE (ed.). QSAR in Environmental Toxicology  II. New York: D. Reidel Publishing Company. pp. 385 391. PHENOLS 9/ 1993 217 LIST OF PHENOLS USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ PHENOLS USED IN THE CALCULATION OF THIS SAR Resorcinol 60.0 0.8 C Resorcinol 100.0 0.81 D Phenol 44.5 1.5 EPA1 Phenol 36.3 1.5 EPA1 Phenol 36.0 1.5 EPA1 Phenol 34.9 1.5 EPA1 Phenol 26.0 1.5 EPA1 Phenol 19.0 1.5 EPA1 Phenol 16.7 1.5 EPA1 Phenol 16.4 1.5 EPA1 Phenol 10.2 1.5 EPA1 Phenol 8.9 1.5 D Phenol 67.5 1.5 D Phenol 29.8 1.5 K Phenol 43.0 1.5 S Phenol 37.0 1.5 V 3 Methoxyphenol 74.0 1.6 V 4 Methoxyphenol 110.0 1.6 V 4 Nitrophenol 14.2 1.9 S 3 Nitrophenol 11.8 1.9 S 4 Nitrophenol 41.0 1.9 H 4 Nitrophenol 6.9 1.9 M 3 Methylphenol 23.1 2.1 S 4 Methylphenol 16.5 2.1 V p Cresol 7.9 2.1 D p Cresol 28.6 2.1 D o Cresol 8.4 2.1 D o Cresol 18.2 2.1 D m Cresol 8.9 2.1 D m Cresol 55.9 2.1 D 2 Chlorophenol 11.2 2.2 K 2 Chlorophenol 13.8 2.2 S 2 Chlorophenol 9.4 2.2 V 2 Allylphenol 15.0 2.2 V 4 Chlorphenol 8.5 2.5 S 3 Chlorophenol 6.4 2.5 K 1 Naphthol 4.6 2.6 V 4 Ethylphenol 10.4 2.7 V 2,6 Dichlorophenol 7.8 2.8 S 2,4 Dimethylphenol 16.6 2.8 H 2 Chloro 4 methylphenol 35.9 2.9 V 2,4 Dichlorophenol 5.5 3.1 S PHENOLS 9/ 1993 218 ____________________________________________________________________________________ ___ CONTINUED. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ PHENOLS USED IN CALCULATION OF THE SAR 4,5 Dichloro 2 methoxy phenol 4.8 3.1 S 2,4 Dichlorophenol 4.2 3.1 K 3,4,5 Trichloro 2,6 dimethoxyphenol 3.4 3.1 S 2,4 Dichlorophenol 7.75 3.1 H 4 Chloro 3 methylphenol 5.72 3.1 V 2,4 Dichlorophenol 7.75 3.1 V 4 Propylphenol 11.0 3.2 V 4 Phenylazophenol 1.17 3.2 V 3,5 Dichlorophenol 2.7 3.3 K Bis( thiophenol) 1.5 3.4 EPA3 2,3,6 Trimethylphenol 0.390 3.4 S 2 Phenylphenol 6.15 3.4 V 4,4'[ oxybis( 2,1 ethane diylthio)] bisphenol 1.5 3.4 EPA4 4 Tert butylphenol 5.15 3.5 V 3,4,5 Trichloro 2 methoxyphenol 2.1 3.6 S 2,4,6 Trichlorophenol 4.55 3.6 V 2,4,6 Trichlorophenol 2.3 3.6 S 2,3,6 Trichlorophenol 5.1 3.8 K 4 chloro 3,5 dimethyl phenol 3.4 3.8 S 4 Phenoxyphenol 4.96 3.8 V Bisphenol A 4.6 3.8 A 2,3,5 Trichlorphenol 1.6 3.9 K 2,4,5 Trichlorophenol 1.2 3.9 S 3,4,5,6 Tetrachloro 2 hydroxyphenol 2.5 3.9 S 4 Tert pentylphenol 2.59 4.0 V 2 Tert butyl 4 methylphenol 2.1 4.1 S 2,3,5,6 Tetrachlorophenol 1.4 4.3 K 2,3,4,6 Tetrachlorophenol 1.1 4.3 S 2,3,4,5 Tetrachlorophenol 0.770 4.6 K Pentachlorophenol 0.380 5.1 K Pentachlorophenol 0.24 5.1 V Pentachlorophenol 0.440 5.1 S 4( Tert octyl) phenol 0.250 5.3 EPA2 4( Tert octyl) phenol 0.210 5.3 EPA2 PHENOLS 9/ 1993 219 4 Nonylphenol 0.140 6.4 V ____________________________________________________________________________________ ____

CONTINUED. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ PHENOLS USED IN CALCULATION OF THE SAR Substituted benzophenone glyceride * 8.0 EPA4 Hindered phenol * 11.0 EPA4 PHENOLS HAVING EXCESS TOXICITY p Benzoquinone 0.125 0.3 D p Benzoquinone 0.045 0.3 D Hydroquinone 0.097 0.8 D Hydroquinone 0.044 0.8 D Catechol 8.9 0.81 D Catechol 3.5 0.81 D ____________________________________________________________________________________ ____

* = No fish mortality in saturated solutions.

A = Alexander et al (1988) C = Curtis and Ward (1981) D = DeGraeve et al (1980) H = Holcombe et al (1984, 1982) K = Konemann and Musch (1981) M = Marking et al (1991) S = Saarikoski and Viluksela (1982) EPA1 = USEPA (1980) EPA2 = USEPA (1984) EPA3 = USEPA (1990) EPA4 = USEPA (1991) V = Veith and Broderius (1987) PHENOLS 9/ 1993 220 PHENOLS 9/ 1993 221 SAR PHENOLS Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 0.451  0.409 log Kow Statistics: N = 48; R 2 = 0.6 Maximum log Kow : 5.5 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for phenols.

Limitations: Phenols which contain the following groups may have excess toxicity compared with the values predicted by this SAR:

1,2 di( OH) groups (e. g., catechol); 1,4 di( OH) groups (e. g., hydroquinone); or 1,4 di(= O) groups (e. g., benzoquinone).

If the log Kow value is greater than 5.5, or if the compound is solid and the LC50 exceeds the water solubility, use SAR with longer duration.

For aminophenols, use the daphnid 48 h LC50 SAR for anilines.

References: Alexander HC, Dill, DC, Smith LW, Guiney PD, and Dorn P. 1988. Bisphenol A: Acute aquatic toxicity. Environ. Toxicol. Chem. 7: 19 26.

Kuhn R, Pattard M, Pernak, K D, and Winter A. 1989. Results of the harmful effects of water pollutants to Daphnia magna in the 21 day reproduction test. Water Res. 23: 501 510.

LeBlanc G. 1980. Acute toxicity of priority pollutants to water flea (Daphnia magna). Bull. Environm. Contam. Toxicol. 24: 684 691.

United States Environmental Protection Agency (USEPA1). 1984. Dynamic 14 day acute toxicity of octylphenol to rainbow trout (Salmo gairdneri). TSCA Section 4( d). Document No. 40 8462075. Washington, DC: OTS Public Files, USEPA. Fiche No. 0507489 (2).

United States Environmental Protection Agency (USEPA2). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, USEPA. PHENOLS 9/ 1993 222 LIST OF PHENOLS USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ PHENOLS USED IN CALCULATION OF THE SAR 3 Hydroxyphenylurea 93.0 0.2 K 4 Acetamidophenol 9.2 0.5 K 4 Hydroxybenzonitrile 15.0 1.6 K 4 Nitrophenol 22.0 1.9 L 2 Chlorophenol 2.6 2.2 L 4 Chlorophenol 4.1 2.5 L 2,4 Dimethylphenol 2.1 2.8 L 3( Trifluoromethyl) phenol 11.0 2.9 K 2,4 Dichlorophenol 2.6 3.1 L 4 Chloro 6 methylphenol 0.290 3.1 L o Phenylphenol 1.5 3.4 K 2,4,6 Trichlorophenol 6.0 3.6 L 2,4 Dichloro 6 methyl phenol 0.430 3.7 L 4 Chloro 3,5 dimethyl phenol 4.5 3.8 K Bisphenol A 10.2 3.8 A 2,4,5 Trichlorophenol 2.7 3.9 L 2,3,4,6 Tetrachlorophenol 0.290 4.3 L 2,3,5,6 Tetrachlorophenol 0.570 4.3 L Pentachlorophenol 0.680 5.1 L 4( Tert octyl) phenol 0.270 5.3 EPA1 3,5 Di tert butylphenol 1.7 5.4 K Substituted benzophenone glyceride * 8.0 EPA2 ____________________________________________________________________________________ ____

* = No daphnid mortalities in saturated solutions.

A = Alexander et al (1988) EPA1 = USEPA1 (1984) EPA2 = USEPA2 (1991) K = Kuhn et al (1989) L = LeBlanc (1980) PHENOLS 9/ 1993 223 SAR PHENOLS Organism: Green Algae Duration: 96 h Endpoint: EC50 (Growth)

Equation: To find the estimated acute toxicity of a phenol, use the neutral organic green algae 96 h EC50 SAR.

Maximum log Kow : 6.4 Maximum MW: 1000.0 Application: The neutral organic green algae 96 h EC50 SAR may be used to estimate toxicity for phenols.

Limitations: Phenols which contain the following groups may have excess toxicity compared with the values predicted by this SAR:

1,2 di( OH) groups (e. g., catechol); 1,4 di( OH) groups (e. g., hydroquinone); or 1,4 di(= O) groups (e. g., benzoquinone).

If the log Kow value is greater than 6.4, or if the compound is solid and the EC50 exceeds the water solubility, use SAR with longer exposure.

For aminophenols, use the green algae chronic value SAR for anilines.

References: Alexander HC, Dill, DC, Smith LW, Guiney PD, and Dorn P. 1988. Bisphenol A: Acute aquatic toxicity. Environ. Toxicol. Chem. 7: 19 26.

Kuhn R and Pattard M. 1990. Results of the harmful effects of water pollutants to green algae (Scenedesmus subspicatus) in the cell multiplication inhibition test. Water Res. 24: 31 38.

United States Environmental Protection Agency (USEPA1). 1984. Dynamic 14 day acute toxicity of octylphenol to rainbow trout (Salmo gairdneri). TSCA Section 4( d). Document No. 40 8462075. Washington, DC: OTS Public Files, USEPA. Fiche No. 0507489 (2).

United States Environmental Protection Agency (USEPA2). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, USEPA. PHENOLS 9/ 1993 224 LIST OF PHENOLS USED TO DEVELOP THE GREEN ALGAE 96 h EC50 SAR. ____________________________________________________________________________________ ____ 96 h EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ PHENOLS USED IN CALCULATION OF THE SAR 3,5 Dimethoxyphenol 110.0 1.4 K 4 Nitrophenol 26.0 1.9 K p Cresol 7.8 2.1 K 2 Chlorophenol 50.0 2.2 K 2 Bromophenol 60.0 2.4 K 2 Nitro para cresol 12.0 2.5 K 4 Chlorophenol 8.0 2.5 K 2,4 Dichlorophenol 11.5 3.1 K 4 Chloro 3 methylphenol >10.0 3.1 K 2,4,6 Trimethylphenol 17.0 3.4 K Bis( thiophenol) 0.740 3.4 EPA2 Bisphenol A 2.7 3.8 A 4( Tert octyl) phenol 1.6 5.3 EPA1 PHENOLS HAVING EXCESS TOXICITY 2 Amino 4 methylphenol 4.6 1.3 K ____________________________________________________________________________________ ____

A = Alexander et al (1988) EPA1 = USEPA1 (1984) EPA2 = USEPA2 (1991) K = Kuhn and Pattard (1990) PHENOLS 9/ 1993 225 SAR PHENOLS Organism: Fish Duration: 30 d Endpoint: Chronic Value Equation: Log ChV (mM/ L) = 0.401  0.652 log Kow Statistics: N = 20; R 2 = 0.94 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for phenols.

Limitations: Phenols which contain the following groups may have excess toxicity compared with the values predicted by this SAR:

1,2 di( OH) groups (e. g., catechol); 1,4 di( OH) groups (e. g., hydroquinone); or 1,4 di(= O) groups (e. g., benzoquinone).

If the log Kow value is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility, use SAR with longer exposure. A test duration of more than 30 days may result in a lower chronic toxicity; at 60 days the toxicity will be 20 x lower than predicted by this SAR for phenols with a log Kow of 1.5 and 4 x lower for phenols with a log Kow of 5.3. For an exposure period of 60 days, a separate SAR has been developed.

For aminophenols, use the fish ChV SAR for anilines.

References: DeGraeve GM, Geiger DL, Meyer JS, and Bergman HL. 1980. Acute and embryo larval toxicity of phenolic compounds to aquatic biota. Arch. Environ. Contam. Toxicol. 9: 557 568.

Hedtke SF, West CW, Allen KN, Norberg King TJ, and Mount DI. 1986. Toxicity of pentachlorophenol to aquatic organisms under naturally varying and controlled conditions. Environ. Toxicol. Chem. 5: 531 542.

Holcombe GW, Phipps GL, and Fiandt JT. 1982. Effects of phenol, 2,4 dimethylphenol, 2,4 dichlorophenol, and pentachlorophenol on embryo, larval, and early juvenile fathead minnows (Pimephales promelas). Arch. Environ. Contam. Toxicol. 11: 73 78.

Marking LL, Howe GE, and Bills TD. 1991. Temperature and pH effects on acute and chronic toxicity of four chemicals to amphipods (Gammarus pseudolimnaeus) and rainbow trout (Oncorhynchus mykiss). EPA/ 600/ X 90/ 286. Gulf Breeze, FL: Envrionmental Research PHENOLS 9/ 1993 226 Laboratory, Office of Research and Development, United States Environmental Protection Agency. August.

Spehar RL, Nelson HP, Swanson MJ, and Renos JW. 1985. Pentachlorophenol toxicity to amphipods and fathead minnows at different test pH values. Environ. Toxicol. Chem. 4: 389 397.

United States Environmental Protection Agency (USEPA1). 1980. Ambient Water Quality Criteria for Phenol. EPA 440 5 80 066. Washington, DC: Criteria and Standards Division, Office of Water Regulations and Standards, USEPA.

United States Environmental Protection Agency (USEPA2). 1984. Dynamic 14 day acute toxicity of octylphenol to rainbow trout (Salmo gairdneri). TSCA Section 4( d). Document No. 40 8462075. Washington, DC: OTS Public Files, USEPA. Fiche No. 0507489 (2).

United States Environmental Protection Agency (USEPA3). 1991. Fish Chronic Toxicity Data Base. Duluth, MN: Environmental Research Laboratory (ERL), Office of Research and Development, USEPA, 6201 Congdon Boulevard, 55804; contact C. L. Russom (218) 720 5500. PHENOLS 9/ 1993 227 LIST OF PHENOLS USED TO DEVELOP THE FISH 30 d ChV SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ PHENOLS USED IN CALCULATION OF THE SAR 2,2' Methylene bis (4 chlorophenol) 0.122 5.0 EPA3 4 Nitrophenol 3.38 1.9 M Phenol 1.4 1.5 D Phenol 2.56 1.5 EPA1 o Cresol 1.8 2.1 EPA3 4 Nitrophenol 2.65 1.9 EPA3 2,4 Dimethylphenol 2.48 2.8 HO 2,4 Dimethylphenol 0.763 2.8 EPA3 p Cresol 1.86 2.1 EPA3 Phenol 2.56 1.5 HO 2 Phenylphenol 1.22 3.4 EPA3 Pentachlorophenol 0.089 5.1 S Pentachlorophenol 0.057 5.1 HO Pentachlorophenol 0.040 5.1 S Pentachlorophenol 0.144 5.1 HE Pentachlorophenol 0.049 5.1 S Pentachlorophenol 0.024 5.1 S 2,4,5 Trichlorophenol 0.232 3.9 EPA3 2,4 Dichlorophenol 0.365 3.1 HO PHENOLS HAVING EXCESS TOXICITY Phenol <0.200 1.5 D 4( Tert octyl) phenol 0.008 5.3 EPA2 ____________________________________________________________________________________ ____

D = DeGraeve et al (1980) EPA1 = USEPA (1980) EPA2 = USEPA (1984) EPA3 = USEPA (1991) HE = Hedtke et al (1986) HO = Holcombe et al (1982) M = Marking et al (1991) S = Spehar et al (1985) PHENOLS 9/ 1993 228 PHENOLS 9/ 1993 229 SAR PHENOLS Organism: Fish Duration: 60 d Endpoint: Chronic Value Equation: Log ChV (mM/ L) = 2.029  0.447 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for phenols.

Limitations: If the log Kow value is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

For aminophenols, use the fish ChV SAR for anilines.

References: DeGraeve GM, Geiger DL, Meyer JS, and Bergman HL. 1980. Acute and embryo larval toxicity of phenolic compounds to aquatic biota. Arch. Environ. Contam. Toxicol. 9: 557 568.

United States Environmental Protection Agency (USEPA). 1984. Dynamic 14 day acute toxicity of octylphenol to rainbow trout (Salmo gairdneri). TSCA Section 4( d). Document No. 40 8462075. Washington, DC: OTS Public Files, USEPA. Fiche No. 0507489 (2).

LIST OF PHENOLS USED TO DEVELOP THE FISH 60 d ChV SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ PHENOLS USED IN CALCULATION OF THE SAR Phenol <0.200 1.5 D 4( Tert octyl) phenol 0.008 5.3 EPA ____________________________________________________________________________________ ____

D = DeGraeve et al (1980) EPA = USEPA (1984) PHENOLS 9/ 1993 230 PHENOLS 9/ 1993 231 PHENOLS 9/ 1993 232 SAR PHENOLS Organism: Daphnid Duration: Endpoint: Chronic Value Equation: Log ChV (mM/ L) = 0.573  0.614 log Kow Statistics: N = 12; R 2 = 0.92 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for phenols.

Limitations: Phenols which contain the following groups may have excess toxicity compared with the values predicted by this SAR:

1,2 di( OH) groups (e. g., catechol); 1,4 di( OH) groups (e. g., hydroquinone); or 1,4 di(= O) groups (e. g., benzoquinone).

3,5 Dimethoxyphenol has an excess toxicity of 18 x that predicted by this SAR.

If the log Kow value is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

For aminophenols, use the daphnid ChV SAR for anilines.

References: Kuhn R, Pattard M, Pernak, K D, and Winter A. 1989. Results of the harmful effects of water pollutants to Daphnia magna in the 21 day reproduction test. Water Res. 23: 501 510.

Oris JT, Winner RW, and Moore MV. 1991. A four day survival and reproduction toxicity test for Ceriodaphnia dubia. Environ. Toxicol. Chem. 10: 217 224.

United States Environmental Protection Agency (USEPA). 1984. Dynamic 14 day acute toxicity of octylphenol to rainbow trout (Salmo gairdneri). TSCA Section 4( d). Document No. 40 8462075. Washington, DC: OTS Public Files, USEPA. Fiche No. 0507489 (2). PHENOLS 9/ 1993 233 LIST OF PHENOLS USED TO DEVELOP THE DAPHNID ChV SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ PHENOLS USED IN CALCULATION OF THE SAR Phenol 4.9 1.5 O 4 Nitrophenol 1.8 1.9 K 4 Methylphenol 1.4 2.1 K 2 Chlorophenol 0.500 2.2 K 2 Bromophenol 1.5 2.4 K 4 Chlorophenol 0.840 2.5 K 2 Nitro para cresol 3.2 2.5 K 2,4 Dichlorophenol 0.290 3.1 K 4 Chloro 3 methylphenol 1.8 3.1 K 2,4,6 Trimethylphenol 0.160 3.4 K 4( Tert octyl) phenol 0.086 5.3 EPA PHENOLS HAVING EXCESS TOXICITY 2 Amino 4 methylphenol 0.400 1.3 K 3,5 Dimethoxyphenol 0.320 1.4 K ____________________________________________________________________________________ ____ PHENOLS 9/ 1993 234 SAR PHENOLS Organism: Green Algae Duration: Endpoint: Chronic Value (Growth)

Equation: To find the estimated chronic toxicity of a phenol, use the neutral organic green algae ChV SAR.

Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: The neutral organic green algae ChV SAR may be used to estimate toxicity for phenols.

Limitations: Phenols which contain the following groups may have excess toxicity compared with the values predicted by this SAR:

1,2 di( OH) groups (e. g., catechol); 1,4 di( OH) groups (e. g., hydroquinone); or 1,4 di(= O) groups (e. g., benzoquinone).

If the log Kow is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

For aminophenols, use the aniline green algae ChV SAR.

References: Kuhn R and Pattard M. 1990. Results of the harmful effects of water pollutants to green algae (Scenedesmus subspicatus) in the cell multiplication inhibition test. Water Res. 24: 31 38.

Slooff W, Canton JH, and Hermens JLM. 1983. Comparison of the susceptibility of 22 freshwater species to 15 chemical compounds. I. (Sub) Acute toxicity tests. Aquatic Toxicology 4; 113 128.

United States Environmental Protection Agency (USEPA1). 1984. Dynamic 14 day acute toxicity of octylphenol to rainbow trout (Salmo gairdneri). TSCA Section 4( d). Document No. 40 8462075. Washington, DC: OTS Public Files, USEPA. Fiche No. 0507489 (2).

United States Environmental Protection Agency (USEPA2). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, USEPA. 5 235 LIST OF PHENOLS USED TO DEVELOP THE GREEN ALGAE ChV SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ PHENOLS USED IN CALCULATION OF THE SAR 3,5 Dimethoxyphenol 40.0 1.4 K 4 Nitrophenol 2.1 1.9 K o Cresol 34.0 2.1 S o Cresol 11.0 2.1 S o Cresol 36.0 2.1 S o Cresol 65.0 2.1 S p Cresol 2.3 2.1 K 2 Chlorophenol 24.0 2.2 K 2 Bromophenol 28.0 2.4 K 2 Nitro p cresol 6.3 2.5 K 4 Chlorophenol 3.0 2.5 K 4 Chloro 3 methylphenol 5.2 3.1 K 2,4 Dichlorophenol 2.4 3.1 K 2,4,6 Trimethylphenol 5.8 3.4 K Bis( thiophenol) 0.300 3.4 EPA2 4( Tert octyl) phenol <0.860 5.3 EPA1 PHENOLS WITH EXCESS TOXICITY 2 Amino 4 methylphenol 0.750 1.3 K ____________________________________________________________________________________ ____

EPA1 = USEPA (1984) EPA2 = USEPA (1991) K = Kuhn and Pattard (1990) S = Slooff et al (1983) PHENOLS, DINITRO 9/ 1993 236 SAR PHENOLS, DINITRO Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 0.285  0.559 log Kow Statistics: N = 4; R 2 = 0.96 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for dinitrophenols and other polynitrophenols.

Limitations: If the log Kow value is greater than 7.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: Veith GD and Broderius SJ. 1987. Structure toxicity relationships for industrial chemicals causing type (II) narcosis syndrome. In: Kaiser KLE (ed.). QSAR in Environmental Toxicology II. Boston, MA: D. Reidel Pub. Co., pp. 385 391.

LIST OF DINITROPHENOLS USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 2,4 dinitrophenol 11.0 1.5 VB 4,6 dinitro o cresol 1.54 2.6 VB 2,4 dinitro 1 naphthol sodium 4.24 3.09 VB ____________________________________________________________________________________ ____

VB = Veith and Broderius (1987) PHENOLS, DINITRO 9/ 1993 237 PHENOLS, DINITRO 9/ 1993 238 SAR PHENOLS, DINITRO Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 0.083  0.632 log Kow Statistics: N = 7; R 2 = 0.85 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for dinitrophenols and other polynitrophenols.

Limitations: If the log Kow value is greater than 7.0, or if the compound is solid and the LC50 exceeds the water solubility, no effects expected at saturation.

References: Hermens J, Canton H, Janssen P, and DeJong R. 1984. Quantitative structure activity relationships and toxicity studies of mixtures of chemicals with anaesthetic potency: Acute lethal and sublethal toxicity to Daphnia magna. Aquatic Toxicology 5: 143 154.

Kuhn R, Pattard M, Pernak K D, and Winter A. 1989. Results of the harmful effects of selected water pollutants (anilines, phenols, aliphatic compounds) to Daphnia magna. Water Research 23: 495 499.

LeBlanc. 1980. Acute toxicity of priority pollutants to water flea (Daphnia magna). Bulletin of Environmental Contamination and Toxicology. 24: 684 691.

LIST OF DINITROPHENOLS USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 2,4,6 trinitrophenol 85.0 1.8 L 2,4,6 trinitrophenol 90.0 1.8 K 2,4 dinitrophenol 4.1 1.9 L 2,4 dinitro 6 methyl phenol 3.1 2.6 L dinitro o cresol 3.3 2.6 H 2 methyl 4,6 dinitrophenol 2.7 2.6 K PHENOLS, DINITRO 9/ 1993 239 ____________________________________________________________________________________ ____

Kuhn = Kuhn et al (1989) H = Hermens et al (1984) L = LeBlanc (1980) PHENOLS, DINITRO 9/ 1993 240 SAR PHENOLS, DINITRO Organism: Fish Duration: 32 d Endpoint: Chronic Value (Survival/ Growth)

Equation: Log ChV (mM/ L) = 1.78  0.552 log Kow Statistics: N = 4; R 2 = 1.0 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for dinitrophenols and other polynitrophenols.

Limitations: If the log Kow is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

References: United States Environmental Protection Agency (USEPA). 1991. Fish Chronic Toxicity Data Base. Duluth, MN: Environmental Research Laboratory (ERL), Office of Research and Development, USEPA, 6201 Congdon Boulevard, 55804; contact C. L. Russom (218) 720 5500.

LIST OF DINITROPHENOLS USED TO DEVELOP THE FISH CHRONIC (ChV) SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 2,4 dinitrophenol 0.278 1.5 D 4,6 dinitro o cresol 0.171 2.3 D 2( 1 methylpropyl)

4,6 dinitrophenol 0.027 3.7 D ____________________________________________________________________________________ ____

D = USEPA (1991) PHENOLS, DINITRO 9/ 1993 241 PHENOLS, DINITRO 9/ 1993 242 SAR PHENOLS, DINITRO Organism: Daphnid Duration: 16 d Endpoint: Chronic Value (Survival/ Reproduction)

Equation: Log ChV (mM/ L) = 0.465  0.654 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for dinitrophenols and other polynitrophenols.

Limitations: If the log Kow is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

References: Hermens J, Canton H, Janssen P, and DeJong R. 1984. Quantitative structure activity relationships and toxicity studies of mixtures of chemicals with anaesthetic potency: Acute lethal and sublethal toxicity to Daphnia magna. Aquatic Toxicology 5: 143 154.

LIST OF DINITROPHENOLS USED TO DEVELOP THE DAPHNID CHRONIC VALUE (ChV) SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Dinitro o cresol 2.1 2.3 H ____________________________________________________________________________________ ____ H = Hermens et al (1984) PHENOLS, DINITRO 9/ 1993 243 POLYMERS, POLYCATIONIC 9/ 1993 244 SAR POLYMERS, POLYCATIONIC Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Determine either the percent amine nitrogen or the number of positive charges per 1000 units of molecular weight and use the appropriate SAR:

1. If the percent amine nitrogen is less than 3.5:

Log LC50 (mg/ L) = 1.3076  0.534 x (percent amine nitrogen)

If the percent amine nitrogen is greater than or equal to 3.5, then the fish 96 h LC50 is 0.27 mg/ L.

2. If the number of positive charges per 1000 units of MW is less than 2.5:

Log LC50 (mg/ L) = 1.3116  0.7606 x (number of positive charges per 1000 MW units)

If the number of positive charges per 1000 units of molecular weight is greater than or equal to 2.5, then the fish 96 h LC50 is 0.27 mg/ L.

Statistics: For the percent amine nitrogen SAR: (less than 3.5% amine nitrogen) N = 12 and R 2 = 0.73, (greater than or equal to 3.5% amine nitrogen) N = 20 and the standard deviation is plus or minus 0.18 logarithmic units; For the number of positive charges/ 1000 units MW SAR: (less than 2.5 charges/ 100 MW) N = 12 and R 2 = 0.73 Minimum MW: 1000.0 Application: These SARs may be used for polycationic polymers which are highly water soluble or dispersible and contain nitrogen which may be protonated and/ or quaternarized. These SARs may be used for polysulfoniums and polyphosphoniums which are dispersible.

Limitations: Polycationic polymers which contain silicon may have limited water solubility or dispersibility. Polycationic polymers which contain anionic groups may be significantly less toxic than predicted by this SAR. For example, a polycationic polymer containing 4.7 percent amine nitrogen (or 3.4 cationic charges per 1000 molecular weight) and anionic groups with a cationic: anionic molar ratio of 1: 1.1, will be about 24 times less toxic than predicted, i. e., fish 96 h LC50 is 6.6 mg/ L.

References: Nabholz JV. 1988. A structure activity relationship for polycationic polymers. Washington, DC: Environmental Effects Branch, Health and POLYMERS, POLYCATIONIC 9/ 1993 245 Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency 20460 0001.

LIST OF COMPOUNDS USED TO DEVELOP THE POLYCATIONIC POLYMER FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ Percent Number of Positive Average 96 h Amine Charges per 1000 Molecular LC50 Nitrogen Units of Mol. Weight Weight (1000) (mg/ L) ____________________________________________________________________________________ ____ 0.7 0.5 1.8 9.2 0.7 0.5 1.8 8.5 0.7 0.5 1.8 3.9 0.7 0.5 100.0 53.0 2.0 1.4 2500.0 0.97 2.0 1.4 2500.0 2.3 2.0 1.4 1100.0 0.64 2.0 1.4 1100.0 1.2 2.1 1.5 19000.0 0.84 3.0 2.1 100 0.94 3.4 2.4 * 0.6 3.4 2.4 * 0.3 6.0 4.3 >5.0 0.15 6.0 4.3 >5.0 0.16 6.0 4.3 >5.0 0.29 8.0 5.7 5.0 0.13 8.0 5.7 5.0 0.22 8.0 5.7 5.0 0.22 9.2 6.6 * 0.5 11.0 7.9 1.8 0.22 12.0 8.6 * 1.9 15.0 10.7 * 0.26 15.0 10.7 * 0.24 17.0 12.1 * 0.45 17.2 12.3 50.0 0.45 20.0 14.3 * 0.32 20.0 14.3 * 0.32 20.0 14.3 * 0.32 20.0 14.3 * 0.32 20.0 14.3 * 0.23 20.0 14.3 * 0.20 ____________________________________________________________________________________ ____* Unavailable at present. POLYMERS, POLYCATIONIC 0/ 1993 246 SAR POLYMERS, POLYCATIONIC Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: The first SAR uses percent amine nitrogen to estimate toxicity while the second SAR uses the number of positive charges per 1000 unites of molecular weight. The toxicity increases rapidly from 0.1 to 2.3 percent amine nitrogen; thereafter, toxicity increases slowing with increasing charge density. The SAR equations used to estimate the acute toxicity are:

1. Log LC50 (mg/ L) = 3.41  1.53 x (percent amine nitrogen)

2. Log LC50 (mg/ L) = 3.43  2.19 x (number of positive charges per 1000 MW units)

Maximum Value: percent amine nitrogen SAR: 2.3% amine nitrogen; number of positive charges/ 1000 MW SAR: 1.6 Minimum MW: 1000.0 Application: This SAR may be used to estimate the toxicity of polycationic polymers which are highly water soluble or dispersible and contain a nitrogen which can be protonated and/ or quaternarized. This SAR may be used for polysulfoniums and polyphosphoniums which are dispersible.

Limitations: Polycationic polymers which contain silicon may have limited water solubility or dispersibility.

Polycationic polymers which contain anionic groups may be significantly less toxic than predicted by this SAR. For example, a polycationic polymer containing 4.7 percent amine nitrogen (or 3.4 cationic charges per 1000 molecular weight) and anionic groups with a cationic: anionic molar ratio of 1: 1.1, will be about 31 times less toxic than predicted, i. e., daphnid 48 h LC50 is 19.8 mg/ L.

References: Nabholz JV. 1988. A structure activity relationship for polycationic polymers. Washington, DC: Environmental Effects Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency 20460 0001. POLYMERS, POLYCATIONIC 9/ 1993 247 LIST OF COMPOUNDS USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ Percent Number of Positive Average 96 h Amine Charges per 1000 Molecular LC50 Nitrogen Units of Mol. Weight Weight (1000) (mg/ L) ____________________________________________________________________________________ ___

0.7 0.5 * 300.0 0.7 0.5 * 310.0 2.0 1.4 * 1.7 8.0 5.7 5.0 0.34 11.0 7.9 1.8 0.58 12.0 8.6 1.2 1.2 15.0 10.7 * 0.26 20.0 14.3 * 0.17 ____________________________________________________________________________________ ____ * Unavailable at present. POLYMERS, POLYCATIONIC 9/ 1993 248 SAR POLYMERS, POLYCATIONIC Organism: Green Algae Duration: 96 h Endpoint: EC50 (Growth)

Equation: The algal 96 h EC50 can be estimated by dividing the equivalent fish 96 h LC50 estimate by 6. In addition, the algal 96 h no effect concentration (NEC; same as GMATC) can be estimated by dividing the algal 96 h EC50 by 2.5.

Minimum MW: 1000.0 Application: This SAR may be used to estimate the toxicity of polycationic polymers which are highly water soluble or dispersible and contain a nitrogen which can be protonated and/ or quaternarized. This SAR may be used for polysulfoniums and polyphosphoniums which are dispersible.

Limitations: Polycationic polymers which contain silicon may have limited water solubility or dispersibility.

Polycationic polymers which contain anionic groups may be significantly less toxic than predicted by this SAR. For example, a polycationic polymer containing 4.7 percent amine nitrogen (or 3.4 cationic charges per 1000 molecular weight) and anionic groups with a cationic: anionic molar ratio of 1: 1.1, will be about 30 times less toxic than predicted, i. e., the algal 96 h EC50 is 1.35 mg/ L.

References: Nabholz JV. 1988. A structure activity relationship for polycationic polymers. Washington, DC: Environmental Effects Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency 20460 0001. POLYMERS, POLYCATIONIC 9/ 1993 249 LIST OF COMPOUNDS USED TO DEVELOP THE GREEN ALGAE 96 h EC50 SAR. ____________________________________________________________________________________ ____ Percent Number of Positive Average 96 h 96 h Amine Charges per 1000 Molecular EC50 NEC Nitrogen Units of Mol. Weight Weight (1000) (mg/ L) (mg/ L) ____________________________________________________________________________________ ____ 0.7 0.5 * 300.0 0.88 8.0 5.7 5.0 0.16 * 11.0 7.9 1.8 0.07 0.034 ____________________________________________________________________________________ ____

* Unavailable at present. SURFACTANTS, ANIONIC 9/ 1993 250 SAR SURFACTANTS, ANIONIC Organism: Fish Duration: 96 h and 28 d Endpoint: LC50 and NEC Equation: Determine the average length of the carbon chain to the nearest tenth and use the SAR equation:

Log LC50 (mg/ L) = [( avg. no. of carbons 16) 2  10.643]/ 12.9346 The fish 28 d no effect concentrations (NEC, GMATC, or chronic value) can be estimated by dividing the estimated acute value derived above by 6.5.

Statistics: N = 14; R 2 = 0.624 Maximum Value: carbon chain length of 18 carbons Minimum Value: carbon chain length of 10 carbons Application: This SAR may be used for the following classes of compounds:

1. Alkyl benzene sulfonates 2. Linear alkyl sulfonates (LAS) 3. Amphoteric surfactants with a sulfonate, phosphonate, or carboxylate terminus 4. Anionic surfactants terminated with phosphates 5. Anionic surfactants Limitations: If the acute or chronic toxicity of linear alkyl benzene sulfonates which vary only in carbon chain length are to be estimated, then the weighted average of carbons in the alkyl chains (excluding the aromatic benzene ring) has to be determined.

References: Nabholz JV. 1985. Standard Environmental Hazard Assessment of PMNs 85 1156/ 1163. Intra agency memorandum to O. Gutenson, Chemical Review and Evaluation Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency, Washington, DC 20460 0001. August. SURFACTANTS, ANIONIC 9/ 1993 251 LIST OF ANIONIC SURFACTANTS USED TO DEVELOP THE FISH LC50 SAR. ______________________________________________________________________________ Number ofFish LC50 Carbons (mg/ L) ______________________________________________________________________________ 10 21.2  47.5 11 11.6 12 1.18  6.5 13 1.11 14 0.25  0.42 16 0.087 18 0.38 _____________________________________________________________________________ SURFACTANTS, ANIONIC 9/ 1993 252 SAR SURFACTANTS, ANIONIC Organism: Daphnid Duration: 48 h and 21 d NEC Endpoint: LC50 and NEC Equation: Determine the average length of the carbon chain to the nearest tenth and use the fish 96 h LC50 SAR equation:

Log LC50 (mg/ L) = [( ave. no. of carbons 16) 2  10.643]/ 12.9346 The daphnid 21 d no effect concentration (NEC, GMATC, or chronic value) can be estimated by dividing the estimated acute value derived above by 6.5.

Statistics: N = 14; R 2 = 0.624 Maximum Value: carbon chain length of 18 carbons Minimum Value: carbon chain length of 10 carbons Application: These SARs may be used for the following classes of compounds:

1. Alkyl benzene sulfonates 2. Alkyl sulfonates 3. Amphoteric surfactants with a sulfonate, phosphonate, or carboxylate terminus 4. Anionic surfactants terminated with phosphates 5. Anionic surfactants Limitations: If the acute or chronic toxicity of linear alkyl benzene sulfonates which vary only in carbon chain length are to be estimated, then the weighted average of carbons in the alkyl chains (excluding the aromatic benzene ring) have to be determined.

References: Nabholz JV. 1985. Standard Environmental Hazard Assessment of PMNs 85 1156/ 1163. Intra agency memorandum to O. Gutenson, Chemical Review and Evaluation Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency, Washington, DC 20460 0001. August. SURFACTANTS, ANIONIC 9/ 1993 253 LIST OF ANIONIC SURFACTANTS USED TO DEVELOP THE DAPHNID LC50 SAR. ______________________________________________________________________________ Number of Daphnid LC50 Carbons (mg/ L) ______________________________________________________________________________ 10 29.55 11 21.15 12 5.88 13 2.63 14 0.68 16 0.11 18 0.12 _____________________________________________________________________________ SURFACTANTS, ANIONIC 9/ 1993 254 SAR SURFACTANTS, ANIONIC Organism: Green Algae Duration: 96 h Endpoint: EC50 and NEC (Growth)

Equation: Determine the average length of the carbon chain to the nearest tenth and use the SAR equation:

Log EC50 (mg/ L) = [( ave. no. of carbons  16) 2  42.466]/ 12.368 The green algae 96 h no effect concentration (NEC, GMATC, or chronic value) can be estimated by dividing the estimated EC50 value by 1.4.

Statistics: N = 14; R 2 = 0.89 Maximum Value: carbon chain length of 18 carbons Minimum Value: carbon chain length of 10 carbons Maximum MW:

Application: These SARs may be used for the following classes of compounds:

1. Alkyl benzene sulfonates 2. Alkyl sulfonates 3. Amphoteric surfactants with a sulfonate, phosphonate, or carboxylate terminus 4. Anionic surfactants terminated with phosphates 5. Anionic surfactants Limitations: If the toxicity of linear alkyl benzene sulfonates which vary only in carbon chain length are to be estimated, then the weighted average of carbons in the alkyl chains (excluding the aromatic benzene ring) have to be determined.

References: Nabholz JV. 1987. Predicting the algal 96 h EC50 from the daphnid and fish SAR for LAS's. Intra agency memorandum to "Whom It May Concern." Washington, DC: Office of Toxic Substances, United States Environmental Protection Agency, Washington, DC, 20460 0001. SURFACTANTS, ANIONIC 9/ 1993 255 DATA FOR A C8 ANIONIC SURFACTANT USED TO DEVELOP THE GREEN ALGAE SAR.

_______________________________________________________________________________ EC50 EC10 Organism (mg/ L) (mg/ L)

_______________________________________________________________________________

Algae 12 8.5 Fish 366 Daphnid 289 _______________________________________________________________________________ SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, MONOALKYL 9/ 1993 256 SAR SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, MONOALKYL Organism: Fish Duration: Acute Endpoint: LC50 (Mortality)

Equation: Determine the average number of carbons in the hydrophobic alkyl chain of the surfactant. If the average length of the carbon chain is between 16 and 24 carbons, use the SAR equation:

Log LC50 (mg/ L) = 0.0918 + 0.023 (average length of carbon chain)

If the length of the carbon chain is at least 10 but less than 16, use the SAR equation:

Log LC50 (mg/ L) = 5.43  0.37 (average length of carbon chain)

Maximum Value: average carbon chain length of 24 carbons Minimum Value: average carbon chain length of 10 carbons Application: This SAR may be applied to monoalkyl (trimethyl) quaternary ammonium surfactants which are dispersible in water. This SAR may be used to estimate toxicity for:

1. monoalkyl cationic surfactants 2. monoalkyl phosphonium surfactants 3. monoalkyl sulfonium surfactants Limitations: This SAR may be used for monoalkyl quaternary ammonium surfactants where the anionic salt has less than 8 carbons in the alkyl chain. If the alkyl chain contains 8 or more carbons, the cationic surfactant and the anionic surfactant will form a strong ion pair. This ion pair will be much less soluble in water and consequently will be less toxic to fish.

References: Nabholz JV. 1987. The SAR for monoalkyl (trimethyl) quaternary ammonium surfactants. Washington, DC: Environmental Effects Branch, Health and Environmental Review Division, Office of Toxic Substances, United States Environmental Protection Agency.

Knauf W. 1973. Summary of the toxicity of surfactants to aquatic organisms. Tenside Detergents 5: 251 255. SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, MONOALKYL 9/ 1993 257 LIST OF MONOALKYL TRIMETHYL AMMONIUM CHLORIDE SURFACTANTS USED TO DEVELOP THE SAR FOR QUATERNARY AMMONIUM SURFACTANTS FOR FISH ____________________________________________________________________________________ ____ Number of Acute LC50 Carbons Species Tested (mg/ L) ____________________________________________________________________________________ ____

10 Golden orfe 68 12 Golden orfe 9.0 14 Golden orfe 2.1 16 Golden orfe 0.36 18 Golden orfe 0.41 21 Golden orfe 0.42 ____________________________________________________________________________________ ____ SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, MONOALKYL 9/ 1993 258 SAR SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, MONOAKYL Organism: Daphnid Duration: Acute Endpoint: LC50 (Mortality)

Equation: Determine the average number of carbons in the hydrophobic alkyl chain of the surfactant. If the average length of the carbon chain is between 16 and 22 carbons, use the SAR equation:

Log LC50 (mg/ L) = 1.64 + 0.115 (average length of carbon chain)

If the length of the carbon chain is at least 10 but less than 16, use the SAR equation:

Log LC50 (mg/ L) = 2.07  0.13 (average length of carbon chain)

Maximum Value: average carbon chain length of 22 carbons Minimum Value: average carbon chain length of 10 carbons Application: This SAR may be applied to monoalkyl (trimethyl) quaternary ammonium surfactants which are dispersible in water. This SAR may be used to estimate toxicity for:

1. monoalkyl cationic surfactants 2. monoalkyl phosphonium surfactants 3. monoalkyl sulfonium surfactants Limitations: This SAR may be used for monoalkyl quaternary ammonium surfactants where the anionic salt has less than 8 carbons in the alkyl chain. If the alkyl chain contains 8 or more carbons, the cationic surfactant and the anionic surfactant will form a strong ion pair. This ion pair will be much less soluble in water and consequently will be less toxic to daphnids.

References: Nabholz JV. 1987. The SAR for monoalkyl (trimethyl) quaternary ammonium surfactants. Washington, DC: Environmental Effects Branch, Health and Environmental Review Division, Office of Toxic Substances, United States Environmental Protection Agency.