ESTIMATING TOXICITY OF INDUSTRIAL CHEMICALS TO AQUATIC ORGANISMS USING STRUCTURE ACTIVITY RELATIONSHIPS Edited by:

Richard G. Clements Contributors:

R. G. Clements J. V. Nabholz M. Zeeman Environmental Effects Branch Health and Environmental Review Division Office of Pollution Prevention and Toxics U. S. Environmental Protection Agency Washington, DC 20460 August 30, 1996 ESTIMATING TOXICITY OF INDUSTRIAL CHEMICALS TO AQUATIC ORGANISMS USING STRUCTURE ACTIVITY RELATIONSHIPS Edited by:

Richard G. Clements Contributors:

R. G. Clements J. V. Nabholz M. Zeeman Environmental Effects Branch Health and Environmental Review Division Office of Pollution Prevention and Toxics U. S. Environmental Protection Agency Washington, DC 20460 August 30, 1996 DISCLAIMER This document has been reviewed and approved for publication by the Office of Pollution Prevention and Toxics, U. S. Environmental Protection Agency. Approval does not signify that the contents necessarily reflect the views and policies of the Environmental Protection Agency, nor does the mention of trade names or commercial products constitute endorsement or recommendation for use. FORWARD to the SECOND EDITION As discussed in the FORWARD to the first edition of Estimating Toxicity of Industrial Chemicals to Aquatic Organisms Using Structure Activity Relationships, the development of predictive ecotoxicology models for industrial chemicals creates challenges that are unique compared to those faced in drug or agrichemical design. Under the requirements of the Toxic Substances Control Act there is, however, no choice but to face these challenges and provide the means to assess the ecological risks of new and existing compounds.

Since releasing their first edition in 1988, the scientists within the Environmental Effects Branch of the Office of Pollution Prevention and Toxics have continued to develop property activity correlations that are relevant for industrial chemicals found in commerce. In publish the second edition of Estimating Toxicity of Industrial Chemicals to Aquatic Organisms Using Structure Activity Relationships, the contributors have once again demonstrated their commitment to share the results of these efforts with the scientific and regulatory community. This second edition contains over 70 additional property activity correlations and is a companion document to ECOSAR, which is a computerized version of the relationships developed by the contributors. Through this on going contribution to the world wide 'structure activity relationship knowledge base', the scientist in the Environmental Effects Branch are also providing the means to identify first order uncertainties in the development and use of these predictive models. The influence of the first and second edition on the application of structure activity relationships and the course of future research in are of environmental toxicology can not be minimized. Of particular interest is the continuing to develop models for chronic effects and to establish objective techniques whereby compounds can be assigned to specific relationships.

Again, I congratulate the contributors to this document for their dedication in implementing structure activity relationships in ecological risk assessments and for fostering the exchange of information that is essential for the advancement of the field.

Steven Bradbury Associate Director for Research Environmental Research Laboratory U. S. Environmental Protection Agency Duluth, Minnesota April, 1995 FORWARD The world of the scientist in a regulatory agency which is responsible for chemical safety is quite different from that in physical organic chemistry, toxicology, or drug design. Nothing highlights the difference quite like the scientists who implement the EPA mandate to review industrial chemicals for health and environmental effects. More conventional research scientists work in data rich areas where chemical models are comparatively precise. Only under the Toxic Substances Control Act (TSCA), implemented by the Office of Toxic Substances, can we find the responsibility to evaluate the broad spectrum of chemical safety with little or no data on either new or existing chemicals.

These scientist responded to the EPA responsibilities by adapting approaches used in drug design and chemistry to predict the environmental behavior and toxicology of chemicals from their structure rather than extensive test data. The Office of Research and Development has enjoyed a tenyear partnership with the Office of Toxic Substances in developing quantitative structure activity relationships to estimate the bioaccumulation potential, the persistence, and the toxicity of chemicals in the environment. Much developmental work remains to be done in efforts to more thoroughly evaluate chronic effects of long term exposure; nonetheless, many relationships are adequate to assist regulatory scientists in making judgements concerning the risks of chemicals.

As we continue to improve our understanding of relationships between chemical structure and effects, the Environmental Effects Branch realized the value of this technology to other scientists in EPA Regions and states. Their initiative to summarize the state of the art in this document and make it available to others is another example of the futuristic planning of this group. The predictive power of the methods included in this document varies with the available data and complexity of the toxicity mechanisms. However, the predictive power will continue to increase over the next decade as new chemical models are formed. I congratulate the contributors to this document for the increasing effort to formulate structure activity relationships from scant data, and for their desire to share this work with others in the scientific and regulatory community.

Gilman D. Veith Director Environmental Research Laboratory U. S. Environmental Protection Agency Duluth, Minnesota Jun, 1988 1 INTRODUCTION For many years, the manufacturers of pharmaceuticals, pesticides, and dyes have used the relationship between chemical structure and a specific effect to search for new chemicals. These relationships are called structure activity relationships (SARs). Under Section 5 of the Toxic Substances Control Act of 1976, EPA must review and evaluate all new chemicals before enter they enter commerce. The Environmental Effects Branch (EEB) of OPPT has been responsible for the assessment and evaluation of these new chemicals and for identifying those chemicals of greatest concern for environmental hazard. Since 1976, of all chemicals submitted to EPA under Section 5 of TSCA, fewer than 5% of the Premanufacture Notices have contained toxicity data pertaining to terrestrial and aquatic organisms. To meet its regulatory mandate, EEB began using SARs in 1979 to estimate the toxicity of chemicals in the absence of test data.

The application of SARs in the field of environmental toxicology is relatively new. Some of the early research work began in the 1960's. During the 1970's, many investigators began examining the relationships among chemical properties and the toxicity to aquatic and terrestrial organisms. Among the leaders in this area was the U. S. EPA Environmental Research Laboratory at Duluth (ERL Duluth) who pioneered research in the development and application of SARs to environmental toxicology. In the mid 1970's they developed and later published the SAR for predicting the bioconcentration of neutral organic compounds in fish based upon the octanol/ water partition coefficient. In 1979, they initiated a long term research program to develop SARs for industrial organic chemicals. Between 1981 and 1983, EEB staff evaluated and adopted 13 of these SARs for use in predicting toxicity to fish, aquatic invertebrates, and green algae. To date, the scientists at ERL Duluth have measured the toxicity of over 800 compounds. From this research, they have developed SARs for at least a dozen classes of compounds to both freshwater and marine fish. Recently, emphasis at ERL Duluth has shifted toward SARs for chronic toxicity with numerous chronic values now being published.

The octanol/ water partition coefficient (Kow ) has been the major attribute used by most investigators to correlate structure and toxic effect. The most frequently used relationship is the logarithm of the Kow versus the logarithm of the median toxicity (LC50 and EC50 ) value. To date the major focus has been centered around the class of industrial organic chemicals known as neutral organics. These compounds are non ionizable, non reactive and neutral with respect to charge; however, SARs have been developed for other classes of chemicals and new ones continue to be derived as data become available.

This manual is intended to accompany an SAR program, called ECOSAR, that has been developed by EEB for use on a personal computer. ECOSAR is menu driven and contains on line help, including a User's Guide. ECOSAR includes all of the chemical classes and SARs contained in this manual. Most toxicity values (in mg/ L) are based on log Kow and molecular weight information supplied by the user, although as discussed below, some SARs require other physical data, such as number of ethoxylates or percent amine nitrogen. ECOSAR may be obtained from the sources listed at the end of the Introduction.

Chemical Classes This manual presents information for deriving toxicity values for four primary classes of chemicals:

(1) Neutral organics that are nonreactive and nonionizable; (2) Organics that are reactive and ionizable and that exhibit excess toxicity in addition to narcosis; (3) Surface active organic compounds such as surfactants and polycationic polymers; and (4) Inorganic compounds including organometallics. 2 Neutral organic compounds that are nonelectrolytic and nonreactive act as anesthetics or narcotics. This class of compounds includes alcohols, ketones, ethers, alkyl halides, aryl halides, aromatic hydrocarbons, aliphatic hydrocarbons, many cyanates, sulfides, and disulfides.

Organic compounds with a more specific mode of toxicity may contain reactive functional groups such as electrophilic moieties. These compounds are more toxic than would be predicted by using an SAR for a narcotic compound. Chemicals which exhibit excess toxicity include acrylates, methacrylates, aldehydes, anilines, beta diketones (linear forms), benzotriazoles, esters, phenols, aziridines, and epoxides. A separate SAR has been developed for each of these classes.

Surface active chemicals may act on the respiratory membranes of aquatic organisms. These chemicals consist primarily of surfactants that can be absorbed through respiratory membranes and charged polymers that cannot be absorbed. SARs have been developed for anionic surfactants such as linear alkyl benzene sulfonates, nonionic surfactants such as alcohol ethoxylates and cationic surfactants, such as ethoxylated beta amine surfactants (ethomeen) and linear N alkyl quaternary ammonium compounds. The SARs for surfactants are parabolic, i. e., toxicity is related to the size of the hydrophobic component in a parabolic manner when the size of the hydrophilic component remains constant. The size of the hydrophobic component, usually a linear alkyl carbon chain, can be estimated by simply counting the number of carbons in the hydrophobic alkyl chain. Maximum toxicity occurs when there are approximately 16 or 17 carbons in the linear alkyl chain. Toxicity for the nonionic surfactants is also affected by the number of ethoxylate units and the size of the hydrophobe and the number of ethoxy groups must be known to use the SAR.

Polycationic polymers include those with primary, secondary, and tertiary amines and/ or quaternary ammoniums, phosphoniums, and sulfoniums. The molecular descriptor used to predict toxicity for these polymers is equivalent charge density as determined from chemical structure, i. e., percent amine nitrogen, number of cationic charges per 1000 units of molecular weight, or cation equivalent weight. These polymers must be water soluble or self dispersing or both.

Quantitative SARs have not been developed for inorganic compounds. However, in lieu of such equations, water quality criteria values have been used to predict their toxicity. Water quality criteria have been developed for several metals. These criteria are usually indicative of the lowest concentration that is believed to be protective of aquatic life in the receiving water. Consequently, most criteria are expressed only for acute or chronic toxicity to freshwater or marine organisms in general. SAR equations will eventually be developed for organometallics based on their Kow values.

Some chemical classes do not have quantitative SARs. These include polyanionic polymers, cationic dyes, and most classes of pesticides. Two classes of polyanionic polymers are known to be toxic to aquatic organisms; polyaromatic sulfonic acids are moderately toxic to aquatic organisms; and polycarboxylic acids are moderately toxic only to green algae. However, the high molecular weight of these polymers indicate that they will not be absorbed through the surface membranes of these organisms and their toxicity is the result of their surface activity and is not correlated with their anionic charge density. Cationic dyes can be absorbed and are known to be highly toxic to aquatic organisms. During acute exposure, the toxicity of these dyes is believed to be mostly the result of their activity on the surface membrane while chronic exposure also results in systemic toxicity. Dyes with delocalized cationic charges may be more toxic, followed by dyes with four localized charges, then three localized charges, etc. Most commercial dyes contain impurities which may, in part, be responsible for some of the toxic effects seen in these dyes. Acid dyes are moderately toxic only to green algae which results more from shading of the algae by the dye rather than from direct toxic effects. Data on which to validate this assumption are lacking in most PMN submissions.

How SARs Are Developed Work sheets were developed to provide pertinent information about each SAR, especially the mathematical procedures for calculating toxicity values based on molecular weight and Kow . Data to develop 3 new SARs are entered in a spreadsheet that allows the SAR equations to be calculated based on a measured toxicity values (in mmoles/ L) and an estimated Kow . Using these estimated values, regression equations can be developed for a class of chemicals, e. g, neutral organics, acrylates, anionic surfactants, etc. Toxicity values for new chemicals may then be calculated by inserting the estimated Kow into the regression equation and correcting the resultant values for the molecular weight of the compound.

As discussed above, the mode of toxic action for most neutral organics appears to be narcosis; however, some organic chemicals have a more specific mode of toxicity with comparable Kow s and molecular weights. For these chemicals, the toxicity is also related to the Kow and as the Kow decreases (i. e., as the chemicals become more water soluble), the amount of excess toxicity compared to neutral organic compounds increases. Consequently, at some higher Kow the toxicity of the compound is not significantly different from the toxicity of the equivalent neutral organic. For organic chemicals which haves excess toxicity and for which are data poor, e. g., amino anilines, a neutral organic data point may be used in addition to the measured toxicity value to give a regression equation. These are the chemicals that have a N= 2 entry under statistics but show only one chemical in the list of chemicals used to develop the SAR. The second point is a neutral organic Kow value. In addition, for some lists of chemicals used to develop the SAR, a single chemical is listed more than once. This is because the chemical has been tested more than once. Each toxicity value is included for the chemical if it provides a reliable data point, i. e., if a second study confirmed a previously derived toxicity value.

To date, over 100 SARs have been developed for over 40 classes of organic chemicals (see Table 1). These chemical classes include neutral organics, surfactants, polymers, and other organic compounds. Most of the SARs are for acute toxicity to fish or daphnids; however, acute and chronic SARs have been developed for other organisms. Some classes, such as acid chlorides, only have one SAR (e. g., fish 96 hour LC50 ), while for other classes such as neutral organics more than 10 SARs have been developed ranging from acute and chronic SARs for fish to a 14 day LC50 for earthworms in artificial soil. New SARs will be added as data become available. This manual will be periodically updated to reflect the additions.

Selecting an Appropriate SAR Selecting the appropriate SAR for a new chemical is based on a variety of chemical specific information. This information includes the exact chemical structure, chemical class, predicted Kow , molecular weight of the compound, physical state, water solubility, number of carbons or ethoxylates or both, and percent amine nitrogen or number of cationic charges or both, per 1000 molecular weight. The most important factor for deriving a SAR is the chemical class as SARs are chemical class specific. An alphabetical listing of chemical classes and appropriate SARs to use for each is included at the conclusion of this section.

To estimate the toxicity to aquatic organisms of neutral, nonreactive, non ionizable organics and organics that exhibit excess toxicity, the Kow and molecular weight are required. The value for the Kow should be obtained from estimated values using the computer program CLOGP, Version 3.3. The range of Kow values are valid to estimate the toxicity is SAR specific and is given for each SAR in a chemical class. In general, when the log Kow is less than or equal to 5.0, valid predictions can be obtained for estimating acute toxicity to aquatic organisms from neutral organic compounds. If the log Kow is greater than 5.0, the decreased solubility of a compound will result in no effects in a saturated solution during a 96 hour test and a longer exposure duration should be used to determine the LC50 . For chronic exposures, the applicable log Kow may be extended up to 8.0. If the log Kow of the compound exceeds 8.0, no adverse effects are 4 Table 1. Existing SARs SAR Class Acute Toxicity Chronic Toxicity Other Fish Daphnid Algae Fish Daphnid Alga e Acid chlorides X Acrylates X X Acrylates, methacrylates X Alcohols, propargyl X Aldehydes X X X X X Amines, aliphatic X X X X Anilines X X X X X Anilines, amino, meta or 1,3 substituted X X X Anilines, amino, ortho or 1,2 substituted X X X Anilines, amino, para or 1,4 substituted X X X X Anilines, dinitroanilines X X X Aziridines X X X Benzenes, dinitro X X X X Benzotriazoles X X X Carbamates X Carbamates, dithio See SAR Title Page Crown Ethers See SAR Title Page Diazoniums, aromatic X Epoxides, monoepoxides X X Epoxides, diepoxides X X Esters X X X X Esters, monoesters, aliphatic X Esters, diesters, aliphatic X Esters, phosphate X Esters, phthalate X X X Hydrazines X X X Hydrazines, semicarbazide, alkyl substituted X Hydrazines, semicarbazides, aryl, meta/ para substituted X Hydrazines, semicarbazides, aryl, ortho substituted X Imides X Ketones, diketones, aliphatic X X X X Malononitriles X SAR Class Acute Toxicity Chronic Toxicity Other Fish Daphnid Algae Fish Daphnid Alga e 5 Neutral organics X X X X X X X Peroxy acids X X Phenols X X X X X X Phenols, dinitrophenols X X X X Polymers, polycationic X X X Surfactants, anionic X X X X X X Surfactants, cationic, quaternary ammonium, monoalkyl X X X Surfactants, cationic, quaternary ammonium, dialkyl X X X X X X Surfactants, ethomeen X X X Surfactants, nonionic X X Thiazolinones, iso X X X X Thiols (mercaptans) X X Triazines, substituted X X Ureas, substituted X for neutral organic compounds in saturated solutions even with long term exposures. Other chemical classes have other upper limits for Kow. For examples, the maximum log Kow for aldehydes is 6.0 and 7.0 for phenols.

Using SARs All SARs contain an equation that predicts the aquatic toxicity of a chemical. Most of the SARs require the user to know the predicted log of the octanol water partition coefficient (Kow). When this number is entered into the equation, a toxicity values in millimoles/ L (mM/ L) is derived. The molecular weight of the subject compound is required to convert the SAR estimates from millimoles/ L to mg/ L. The ECOSAR program does this automatically, however, manual estimates require that conversions be made. For example, the equation for predicting the fish 96 hour LC50 values for neutral organics is:

Using 1,1' biphenyl (CASRN [92 52 4] as a representative chemical, the estimated log Kow for this compound is 4.0, to give a log LC50 of 2.01. Taking the antilog of 2.01, gives an LC50 value of 0.009 mM/ L. However, to express the toxicity of the 1,1' biphenyl as mg/ L, the toxicity must be multiplied by the molecular weight of the compound which is 154.20, to give a final toxicity value of 1.5 mg/ L. Conversions from mM/ L to mg/ L are not necessary for compounds and equations (e. g., surfactants, polymers) that do not use Kow as the input parameter for toxicity.

Molecular weight is also used to determine the absorption cutoff limit for aquatic organisms. As the molecular weight of a chemical increases above 600, passive absorption through respiratory membranes decreases significantly. Therefore, for chemicals with molecular weights above 1000, it has been assumed that such absorption is negligible. For surface active chemicals such as cationic polymers, molecular weight 6 is not limiting because the toxic effect is not due to absorption, for example, some polycationic polymers with molecular weights in excess of 1,000,000 are highly toxic to aquatic organisms.

An important aspect of determining the toxicity of a compound is knowing the water solubility. The water solubility of a compound can be compared with the SAR toxicity value derived for that compound. If the toxicity value is significantly greater than the measured or predicted maximum water solubility, then an effect is not expected to occur in a saturated solution. In addition, a determination of the physical state (liquid, solid, or gas) of the compound is helpful in selecting an SAR. SARs currently used by EEB were developed using toxicity data on chemicals that are liquids at room temperature (25 EC). If an organic chemical is a solid at room temperature, then the melting point should be known because of the effect it has on water solubility, i. e., assuming Kow is constant, the higher the melting point of a neutral organic chemical, the lower its water solubility. For other chemicals such as surfactants, water dispersibility is used; however, for practical purposes, water solubility and dispersibility are considered to be synonymous.

To determine the toxicity of a surfactant, it is necessary to know the number of carbon atoms in the alkyl chain for anionic surfactants or the number of ethoxylate units in the compound if it is an cationic (ethomeen) or nonionic surfactant. For cationic quaternary ammonium surfactants, the toxicity is based on the average length of a linear carbon chain, if the chain length is between 10 and 24 carbons long. The surfactant SARs developed by EEB are based on surfactants where the hydrophobic component is composed of a single linear chain of carbons and/ or chains of ethoxylate units. Surfactants that have complex hydrophobic components are assessed by calculating the Kow of the complex hydrophobic component alone and determining which aliphatic alkyl (carbon) chain has an equivalent Kow . Toxicity predictions are based on this equivalent chemical structure. See the SAR for cationic dialkyl quaternary ammonium surfactants for more details on these calculations.

For polycationic polymers, it is necessary to calculate the percent amine nitrogen and/ or number of cationic charges per 1000 molecular weight.

For inorganic and organometallic compounds, only the molecular weight of the compound is used for calculating the toxicity value. Acute and/ or chronic toxicity values will be expressed in mg/ L, and further conversions and/ or calculations are not necessary.

Reliability of SARs As may be seen by reviewing the chemicals used to derive the individual SARs in this manual, some chemical classes have a greater number of chemicals with accompanying toxicity values than do others. For example, the neutral organic 96 hour fish LC50 SAR was based on toxicity values for over 60 chemicals, whereas, the fish 96 hour LC50 SAR for propargyl alcohols was based on only one toxicity value. In the cases where there is only one toxicity value for a chemical class, the SAR is based on the line drawn between the one toxicity value and the maximum toxicity value of a neutral organic compound. Obviously SARs developed using only one or two toxicity values taken from the literature or premanufacture notices may not have the same reliability as an SAR developed from a larger toxicity database; however, on a regulatory basis this is the best estimate that can be scientifically achieved.

To determine how reliable the SARs in this manual are, Nabholz et al. (1993) conducted a validation study which compared the predicated toxicity values of chemicals with their measured toxicity values. Several chemical classes were included in the study: neutral organics, organic chemicals which show excess toxicity compared with neutral organics of a similar structure, anionic surfactants, cationic surfactants, polycationic polymers, cationic dyes, acid dyes, polyanionic monomers which are strong chelators of nutrient elements, and compounds which undergo hydrolysis (e. g., acid chlorides and alkyloxysilanes). In all, test data from 462 chemicals were used in the validation study. SARs for acute and chronic toxicity for fish, daphnids, and green algae were reviewed. Validation was expressed as a ratio, i. e., predicted toxicity: measured toxicity. A ratio of 1.0 would indicate that the predictions were perfectly accurate, a ratio 7 of less than 1.0 would indicate an over prediction of toxicity, and a ratio of more than 1.0 would indicate that SARs were under predicting the toxicity of the chemicals. The results of the study indicated that the algal chronic effect was most accurately predicted (ratio 1.07) while the fish chronic value was the least reliable (ration 0.24). The fish 96 hour LC50 ratio was 0.64, the daphnid 48 hour LC50 was 0.79, and the algae 96 hour EC50 was 0.81. Work on validating the SARs is continuously ongoing in EEB.

FURTHER DISCUSSION NEEDED FOR USE OF NEAREST ANALOG; WHY GASES DON'T HAVE SAR; AND RADIONUCLIDES Sources for ECOSAR ECOSAR: Computer Program and User's Guide for Estimating the Ecotoxicity of Industrial Chemicals Based on Structure Activity Relationships (Publication Number EPA 748 R 93 002) is available from the following sources:

! National Center for Environmental Publications and Information U. S. Environmental Protection Agency 26 West Martin Luther King Drive Cincinnati, OH 45268 (513) 569 7562 ! National Technical Information Service U. S. Department of Commerce 5285 Port Royal Road Springfield, VA 22161 (703) 487 4650 References Clements, RG, Nabholz, JV, Johnson, DW, Zeeman, M. 1993. The Use and Application of QSARs in the Office of Toxic Substances for Ecological Hazard Assessment of New Chemicals. In: Landis, WG, Hughes, JS, and Lewis, MA, eds. Environmental Toxicology and Risk Assessment, ASTM STP 1179. Philadelphia, PA: American Society for Testing and Materials. pp. 56 64.

Nabholz, JV, Clements, RG, Zeeman, MG, Osborn, KC, Wedge, R. 1993. Validation of Structure Activity Relationships Used by the USEPA's Office of Pollution Prevention and Toxics for the Environmental Hazard Assessment of Industrial Chemicals. In: Gorsuch, JW, Dwyer, FJ, Ingersoll, CG, and LaPoint, TW, eds. Environmental Toxicology and Risk Assessment: 2nd Vol. ASTM STP 1216. Philadelphia, PA: American Society for Testing and Materials. pp. 571 590.

Nabholz, JV, Miller, P, Zeeman, M. 1993. Environmental Risk Assessment of New Chemicals Under the Toxic Substances Control Act (TSCA) Section Five. In: Landis, WG, Hughes, JS, and Lewis, MA, eds. Environmental Toxicology and Risk Assessment, ASTM STP 1179. Philadelphia, PA: American Society for Testing and Materials. pp. 40 55. 8 9 CHEMICAL CLASSES AND APPLICABLE SARs Chemical Class SAR to Use ACETATES Use SAR for ESTERS ACETYLENIC CARBAMATES No SAR available, excess toxicity ACID CHLORIDES Use SAR for ACID CHLORIDES ACID DYES with ONE ACID Some are moderately toxic to fish and daphnids, others are not; No SAR available, Use nearest analog ACID DYES with TWO ACIDS Some are moderately toxic to fish and daphnids, others are not; No SAR available, Use nearest analog ACID DYES with THREE ACIDS Only moderately toxic to green algae due to the indirect effect of shading; shading inhibits growth due to the colored water; Use nearest analog based on chemical structure, color, and intensity of color.

ACRYLAMIDES and SUBSTITUTED ACRYLAMIDES Excess toxicity, Use toxicity data for acrylamides with MW adjustment ACRYLATES (log Kow <5.0) Use SAR for ACRYLATES ACRYLATES (log Kow >5.0) Use SAR for NEUTRAL ORGANICS ACRYLATES, METHACRYLATES Use SAR for ACRYLATES, METHACRYLATES ACTINIUM No SAR available ALCOHOLS Use SAR for NEUTRAL ORGANICS ALCOHOLS, PROPARGYL Use SAR for ALCOHOLS PROPARGYL ALDEHYDES Use SAR for ALDEHYDES, R C(= O) H, ALDEHYDES, VINYL No SAR available; some exhibit excess toxicity, e. g., acrolein, ALIPHATIC AMINES Use SAR for AMINES, ALIPHATIC ALIPHATIC DIESTERS Use SAR for ESTERS, DI, ALIPHATIC ALIPHATIC DIKETONES, LINEAR Use SAR for KETONES, DI, ALIPHATIC ALIPHATIC HYDROCARBON, á HYDROXY ß NITRO SUBSTITUTED or ALIPHATIC HYDROCARBON, 1 HYDROXY 2 NITRO SUBSTITUTED Excess toxicity towards algae, e. g., tris( hydroxymethyl) nitromethane ALIPHATIC MONOESTERS Use SAR for ESTERS ALIPHATIC HYDROCARBONS Use SAR for NEUTRAL ORGANICS Straight chain or cycloalkane, ALKANES, CYCLO Use SAR for NEUTRAL ORGANICS ALKANES, STRAIGHT & BRANCHED Use SAR for NEUTRAL ORGANICS ALKENES Use SAR for NEUTRAL ORGANICS ALKYLANILINES Use SAR for ANILINES ALKYL BENZENE SULFONATES Use SAR for SURFACTANTS, ANIONIC ALKYL ESTERS OF CARBAMIC ACID No SAR available ALKYL HALIDES Use SAR for NEUTRAL ORGANICS ALKYL NITROGEN ETHOXYLATES Use SAR for SURFACTANTS, ETHOMEEN ALKYL SULFONATES Use SAR for SURFACTANTS, ANIONIC ALKYL SULFONATES AND CARBOXYLIC ACID ALLYL CYANIDES Use SAR for MALONONITRILES ALLYL DIESTERS Use SAR for ESTERS , DI, ALIPHATIC 10 ALLYL ESTER Use SAR for ESTERS ALLYL HALOGENS No SAR available ALLYL CHLORIDES show excess toxicity, ALLYL BROMIDES are even more toxic ALKYNES Use SAR for NEUTRAL ORGANICS ALLYL, NITRILES ALUMINUM Use SAR for ALUMINUM AMERICIUM No SAR available AMIDES, VINYL No SAR available. Excess toxicity, Use toxicity data for arcylamides with MW adjustment AMINES, ALIPHATIC, PRIMARY Use SAR for AMINES, ALIPHATIC when log Kow < 7.0, Use nearest analog when log Kow > 7.0 AMINES, ALIPHATIC, SECONDARY Use SAR for AMINES, ALIPHATIC when log Kow < 7.0, Use nearest analog when log Kow > 7.0 AMINES, ALIPHATIC, TERTIARY Use SAR for AMINES, ALIPHATIC when log Kow < 7.0, Use nearest analog when log Kow > 7.0 AMINES, ALIPHATIC, QUATERNARY, SURFACTANT Use SAR for SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, MONOALKYL AMINES, ALIPHATIC, QUATERNARY, NOT A SURFACTANT Calculate Kow for the tertiary amine and Use SAR for AMINES, ALIPHATIC when log Kow < 7.0, nearest analog when log Kow > 7.0; or Use nearest analog method. AMINES, SCHIFF BASES No SAR available AMINES, AROMATIC Use SAR for ANILINES AMINO PHENOLS Use SAR for ANILINES AMINOTRIAZOLES AMPHOTERIC DYES If charges are balanced, low toxicity towards fish and daphnids, and shading only towards algae; if more cationic than anionic, see CATIONIC DYES; and if more anionic than cationic, see ACID DYES ANILINES Use SAR for ANILINES ANILINES, ALKYL Use SAR for ANILINES ANILINES AR NH2 with N substitutions Use SAR for NEUTRAL ORGANICS ANILINES, AMINO, META, OR 1,3 SUBSTITUTED Use SAR for ANILINES, AMINO, META, OR 1,3 SUBSTITUTED ANILINES, AMINO, ORTHO, OR 1,2 SUBSTITUTED Use SAR for ANILINES, AMINO, ORTHO, OR 1,2 SUBSTITUTED ANILINES, AMINO, PARA, OR 1,4 SUBSTITUTED Use SAR for ANILINES, AMINO, PARA OR 1,4 SUBSTITUTED ANILINES, DINITRO Use SAR for ANILINES, DINITRO ANILINES, MONOHYDROXY Use SAR for ANILINES ANILINES, POLYNITRO Use SAR for ANILINES, DINITRO ANTIMONY No SAR available; however water quality criteria may be used ARGON Gas; No SAR available AROMATIC DIAZONIUMS Use SAR for DIAZONIUMS, AROMATIC ARSENIC( III) Use SAR for ARSENIC 11 ARYL HALIDES Use SAR for NEUTRAL ORGANICS ASTATINE No SAR available AZIRIDINES Use SAR for AZIRIDINES, AZO DYES No SAR available; see DYES BARIUM No SAR available BENZENE, DINITRO Use SAR for BENZENES, DINITRO BENZENEAMINES Use SAR for ANILINES BENZOATES Use SAR for ESTERS BENZOTRIAZOLES Use SAR for BENZOTRIAZOLES BENZOTRIAZOLES with free NH Use SAR for BENZOTRIAZOLES, has excess toxicity, BENZOTRIAZOLES with N alkyl substitution Use SAR for NEUTRAL ORGANICS BENZOTRIAZOLES with N thiol substitution No SAR available BENZOYL PEROXIDES Use SAR for PEROXY ACIDS, RC(= O) OOC(= O) R, excess toxicity, BERKELIUM No SAR available BERYLLIUM Use SAR for BERYLLIUM BIPHENYLS, POLYBROMINATED Use SAR for NEUTRAL ORGANICS BISMUTH No SAR available BORON Use SAR for BORON BROMINE No SAR available CADMIUM Use SAR for CADMIUM CALCIUM No SAR available CALIFORNIUM No SAR available CAPROLACTAMS Use SAR for NEUTRAL ORGANICS CARBAMATES No SAR available CARBAMATES, BIS( ETHYL)

JOINED AT NRN BY ALKYL OR ARYL GROUPS No SAR available CARBAMATES, ETHYL, N ALKYL OR ARYL SUBSTITUTED No SAR available CARBAMATES, BIS OR TRIS, ESTERIFIED ON A SINGLE PHENYL RING No SAR available CARBAMATES, THIO No SAR available CARBON No SAR available CARBOXYLIC ACIDS CATIONIC DYES No SAR available, Use nearest analog, MWs can be over 1000 CERIUM No SAR available CESIUM Use SAR for CESIUM CHLORINATED HYDROCARBONS Use SAR for NEUTRAL ORGANICS CHLORINE Use SAR for CHLORINE CHLOROANILINES Use SAR for ANILINES CHLOROFLUOROCARBONS (CFCs) Use SAR for NEUTRAL ORGANICS CHROMIUM Use SAR for CHROMIUM CHROMIUM( III) Use SAR for CHROMIUM CHROMIUM( VI) Use SAR for CHROMIUM COBALT Use SAR for COBALT COPPER Use SAR for COPPER CROWN ETHERS See SAR for CROWN ETHERS 12 CURIUM No SAR available CYANIDE, VINYL No SAR available, R C= C C/N, e. g., acrylonitrile, fumaronitrile, have excess toxicity, CYANATES No SAR available, (NCO R) or (R OCN), excess toxicity, Use nearest analog CYCLIC DIKETONES Use SAR for NEUTRAL ORGANICS CYCLOALKANES Use SAR for NEUTRAL ORGANICS CYCLODIENE Use SAR for NEUTRAL ORGANICS DIAMINES, PHENYLENE (META OR 1,3 SUBSTITUTED) Use SAR for ANILINES, AMINO, META, OR 1,3 SUBSTITUTED DIAMINES, PHENYLENE (ORTHO OR 1,2 SUBSTITUTED) Use SAR for ANILINES, AMINO, ORTHO OR 1,2 SUBSTITUTED DIAMINES, PHENYLENE (PARA OR 1,4 SUBSTITUTED) Use SAR for ANILINES, AMINO, PARA OR 1,4 SUBSTITUTED DIAZONIUMS, ALIPHATIC No SAR available (R N/N A), (very explosive and are used as synthesizing agents) DIAZONIUMS, AROMATIC Use SAR for DIAZONIUM, AROMATIC( AR N/N AR), DICARBOXYLIC ALIPHATIC ESTERS Use SAR for ESTERS DIEPOXIDES Use SAR for EPOXIDES, DI DIESTER, ALLYL No SAR available R C C= C C( O C(= O) C R) O C(= O) C R) excess toxicity e, g., 2 propene 1,1 diol, diacetate, 1000X more toxic than an equivalent NEUTRAL ORGANIC, DIESTERS, AROMATIC OR ALIPHATIC/ AROMATIC Use SAR for ESTERS, PHTHALATE DIKETONES, á, Ã diketone or 1,3 diketones, linear Use SAR for KETONES, DI, ALIPHATIC; e. g., 2,4 pentanediols, excess toxicity DIKETONES, 1,3 diketones, cyclic Use SAR for NEUTRAL ORGANICS DINITROANILINES Use SAR for ANILINES, DINITRO DINITROBENZENES Use SAR for BENZENES, DINITRO DINITROPHENOLS Use SAR for PHENOLS, DINITRO DIPHENOLS Use SAR for PHENOLS DISPERSE DYES Use SAR for NEUTRAL ORGANICS DISULFIDES Use SAR for NEUTRAL ORGANICS DISULFIDE, PHENYL No SAR available, excess toxicity, DITHIOCARBAMATES See SAR for CARBAMATES, DITHIO DITHIOCARBAMATES, POLY No SAR available, excess toxicity, DYES see ACID DYES if ANIONIC DYES; see CATIONIC DYES if cationic; see NEUTRAL DYES if neutral; and see AMPHOTERIC DYES if both cationic and anionic; MWs can be over 1000 for CATIONIC DYES, AMPHOTERIC DYES, and ACID DYES; MWs of NEUTRAL DYES have to be less than 1000 for toxicity towards fish and daphnids; toxicity to green algae is based on color and intensity of color, and is an indirect effect DYSPROSIUM No SAR available ERBIUM No SAR available EPOXIDES, AZIRIDINES Use SAR for AZIRIDINES 13 EPOXIDES, DIEPOXIDES Use SAR for EPOXIDES , DI EPOXIDES, MONOEPOXIDES Use SAR for EPOXIDES , MONO EPOXIDES, POLYEPOXIDES Use SAR for EPOXIDES, DI ESTERS (log Kow <5.0) Use SAR for ESTERS ESTERS (log Kow >5.0) Use SAR for NEUTRAL ORGANICS ESTERS Use SAR for ESTERS, RC(= O) OR, ESTER, ALLYL Use SAR for ESTERS, R C= C C O C(= O) C R, excess toxicity, ESTERS, á HALO No SAR available, C O C(= O) C X, excess toxicity, BROMIDES are more toxic than CHLORIDES ESTERS, DICARBOXYLIC, ALIPHATIC Use SAR for ESTERS ESTERS, DIESTERS, ALIPHATIC Use SAR for ESTERS , DI, ALIPHATIC ESTERS, METHANESULFONATES Use SAR for ESTERS ESTERS, PHOSPHATE Use SAR for ESTERS, PHOSPHATE ESTERS, PHOSPHINOTHIOIC ACID, TRISUBSTITUTED No SAR Available, R O P(= S)( O R) R, pesticide, Use nearest analog ESTERS, PHOSPHINOTHIOIC ACID, DISUBSTITUTED FREE ACID Use SAR for SURFACTANTS, ANIONIC if alkyl chains are long; if alkyl chains are short, use nearest analog (R O P(= S)( OH) R) ESTERS, PHOSPHINOTHIOIC ACID, MONOSUBSTITUTED FREE DIACID Use SAR for SURFACTANTS, ANIONIC if alkyl chains are long; if alkyl chains are short, Use nearest analog (HO P(= S)( OH) R) ESTERS, PHOSPHOROTHIOIC, MONOESTER WE NEED A DESCRIPTION FOR THIS; USES BOTH ANIONIC SURFACTANT AND DIESTER SARS ESTERS, PHOSPHOROTHIOIC, MONOSUBSTITUTED ESTER Use SAR for SURFACTANTS, ANIONIC if alkyl chain is long; if alkyl chain is short, Use nearest analog (R OP S)( OH) OH) ESTERS, PHOSPHOROTHIOIC, DISUBSTITUTED ESTER Use SAR for SURFACTANTS, ANIONIC, if alkyl chain is long, if alkyl chain is short, Use nearest analog ESTERS, PHOSPHOROTHIOIC, TRIESTER Use SAR for ESTERS, PHOSPHATE ESTERS, PHOSPHOROTHIOIC, TRISUBSTITUTED Use SAR for ESTERS, PHOSPHATE ESTERS, PHTHALATE Use SAR for ESTERS, PHTHALATE ESTERS, POLY Use SAR for ESTERS ESTERS, PROPARGYLIC No SAR available, have excess toxicity ESTERS, SULFONATE Use SAR for ESTERS ESTERS, TRIALKYL PHOSPHATE Use SAR for ESTERS, PHOSPHATE ESTERS, VINYL No SAR available, excess toxicity EINSTEINIUM No SAR available ETHERS Use SAR for NEUTRAL ORGANICS ETHOXYLATES, ALKYL Use SAR for SURFACTANTS, NONIONIC EUROPIUM No SAR available FATTY ACIDS Use SAR for SURFACTANTS, ANIONIC FERMIUM No SAR available FLUORINE No SAR available FRANCIUM No SAR available 14 GADOLINIUM No SAR available GALLIUM No SAR available GERMANIUM Use SAR for GERMANIUM GOLD Use SAR for GOLD GUANIDINE Use SAR for AMINES, ALIPHATIC HAFNIUM No SAR available HALIDES, ALKYL Use SAR for NEUTRAL ORGANICS HALIDES, ARYL Use SAR for NEUTRAL ORGANICS HALOGENATED FLUOROCARBONS Use SAR for NEUTRAL ORGANICS HELIUM No SAR available HFCs Use SAR for NEUTRAL ORGANICS HOLMIUM No SAR available HYDRAZIDES Use SAR for HYDRAZINES HYDRAZINES Use SAR for HYDRAZINES HYDRAZINES, CARBOXYLIC (FREE) ACID SUBSTITUTION No SAR available, about 10 times less toxic than HYDRAZINES HYDRAZINES, SEMICARBAZIDES, ARYL, META/ PARA SUBSTITUTED Use SAR for SEMICARBAZIDES, ARYL, META/ PARA SUBSTITUTED HYDRAZINES, SEMICARBAZIDES, ARYL, ORTHO SUBSTITUTED Use SAR for SEMICARBAZIDES, ARYL, ORTHO SUBSTITUTED HYDRAZONES Use SAR for HYDRAZINES HYDROCARBONS, AROMATIC Use SAR for NEUTRAL ORGANICS HYDROCARBONS, AROMATIC, HALOGENATED Use SAR for NEUTRAL ORGANICS HYDROCARBONS, ALIPHATIC, HALOGENATED Use SAR for NEUTRAL ORGANICS HYDROGEN No SAR available; toxicity is based on pH ********* HYDROQUINONES or PARA HYDROXY PHENOL No SAR available, excess toxicity IMIDES Use SAR for IMIDES INDIUM No SAR available INDOLES, HALOGENATED Use SAR for NEUTRAL ORGANICS IODINE No SAR available IRIDIUM No SAR available IRON Use SAR for IRON ISOCYANATES, MONO AND DI ISOCYANATES (R NCO) and ISOTHIOCYANATES No SAR available, excess toxicity if very water soluble. Use nearest analog ISOTHIAZOLINONES Use SAR for THIAZOLINOES, ISO KETONES, á HALO No SAR available, excess toxicity KETONES, MONO Use SAR for NEUTRAL ORGANICS KETONES, DIKETONES, ALIPHATIC Use SAR for KETONES, DI Aliphatic KRYPTON No SAR available LANTHANUM Use SAR for LANTHANUM LAWRENCIUM No SAR available LEAD Use SAR for LEAD LINALOOLS Use SAR for NEUTRAL ORGANICS LINEAR ALKYL BENZENES Use SAR for SURFACTANTS, ANIONIC LINEAR ALKYL BENZENE 15 SULFONATES Use SAR for SURFACTANTS, ANIONIC LINEAR ALKYL SULFONATES Use SAR for SURFACTANTS, ANIONIC LITHIUM No SAR available LUTETIUM No SAR available MAGNESIUM No SAR available MALEIMIDES Use SAR for IMIDES MALONONITRILES Use SAR for MALONONITRILES MANGANESE No SAR available MENDELEVIUM No SAR available MERCAPTANS/ THIOLS Use SAR for THIOLS; (R SH) MERCAPTOBENZOTRIAZOLES: No SAR available , excess toxicity MERCURY Use SAR for MERCURY METHACRYLAMIDES No SAR available, less toxic than ACRYLAMIDES and SUBSTITUTED ACRYLAMIDES METHACRYLATES (log Kow <5.0) Use SAR for METHACRYLATES METHACRYLATES (log Kow >5.0) Use SAR for NEUTRAL ORGANICS METHANESULFONATES Use SAR for ESTERS MOLYBDENUM Use SAR for MOLYBDENUM MONOEPOXIDES Use SAR for EPOXIDES, MONO NEON No SAR available NEUTRAL DYES Use SAR for NEUTRAL ORGANICS NEUTRAL ORGANICS Use SAR for NEUTRAL ORGANICS NEODYMIUM No SAR available NEPTUNIUM No SAR available NICKEL Use SAR for NICKEL NIOBIUM No SAR available NITRILES Use SAR for NEUTRAL ORGANICS NITRILES, ALLYL Use SAR for MALONONITRILES NITRILES, VINYL Use SAR for MALONONITRILES NITROBENZENES, DINITROBENZENES Use SAR for BENZENES, DINITRO NITROGEN No SAR available NITROSO COMPOUNDS No SAR available, excess toxicity NOBELIUM No SAR available OSMIUM No SAR available OXYGEN No SAR available PALLADIUM No SAR available PEROXY ACIDS Use SAR for PEROXY ACIDS PHENOLS Use SAR for PHENOLS PHENOLS, AMINO Use SAR for ANILINES PHENOLS, DI Use SAR for PHENOLS PHENOLS, DINITRO Use SAR for PHENOLS, DINITRO PHENOLS, HALOGENATED Use SAR for PHENOLS PHENOL, META HYDROXY Use SAR for PHENOLS PHENOL, ORTHO HYDROXY No SAR available, CATECHOL, 16 times excess fish acute toxicity PHENOL, PARA HYDROXY or HYDROQUINONE No SAR available, 1400 times excess fish acute toxicity PHENOLS, POLY Use SAR for PHENOLS PHENOLS, SUBSTITUTED Use SAR for PHENOLS PHENYLENEDIAMINES Use SAR for ANILINES, AMINO ******** PHOSPHINOTHIOIC ACID ESTERS, DISUBSTITUTED FREE ACID Use SAR for SURFACTANTS, ANIONIC 16 PHOSPHINOTHIOIC ACID ESTERS, MONOSUBSTITUTED FREE ACID Use SAR for SURFACTANTS, ANIONIC PHOSPHITES No SAR available, excess toxicity PHOSPHONIUM Use SAR for SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM if a surfactant; if not a surfactant use nearest analog: SULFONIUM or QUATERNARY AMMONIUM analogs are acceptable PHOSPHOROTHIOIC ESTERS, DIESTER Use SAR for SURFACTANTS, ANIONIC PHOSPHOROTHIOIC ESTERS, MONOESTER Use SAR for SURFACTANTS, ANIONIC PHOSPHORUS Use SAR for PHOSPHORUS PLATINUM Use SAR for PLATINUM PLUTONIUM No SAR available POLONIUM No SAR available POLYANIONIC MONOMERS No SAR available, monomers with two or more acid groups and which act like organic acid chelators, Use nearest analog POLYAROMATIC HYDROCARBONS Use SAR for NEUTRAL ORGANICS POLYBROMINATED BIPHENYLS Use SAR for NEUTRAL ORGANICS POLYCATIONIC POLYMERS Use SAR for POLYMERS, POLYCATIONIC POLYEPOXIDES Use SAR for EPOXIDES, DI,

POLYISOCYANATES No SAR available, if water solubility is 13 mg/ L or less, then no effects at saturation; these chemicals will polymerize: one NCO will hydrolyze to the amine and the amine will react with another NCO to form a urethane; a crosslinked polymer will be formed POLYMERS, POLYNONIONIC No SAR available, low environmental hazard. POLYMERS, POLYANIONIC, POLY( CARBOXYLIC ACID) No SAR available, Use nearest analog POLYMERS, POLYANIONIC, No SAR available, Use nearest analog POLY( ACRYLIC ACID) POLYMERS, POLYANIONIC, No SAR available, Use nearest analog POLY( METHACRYLIC ACID) POLYMERS, POLYANIONIC, POLY( AROMATIC SULFONIC ACID) No SAR available, Use nearest analog POLYMERS, POLYANIONIC, POLY( ALIPHATIC SULFONIC ACID) No SAR available, Use nearest analog POLYMERS, POLYCATIONIC Use SAR for POLYMERS, POLYCATIONIC POLYMERS, POLYAMINE Use SAR for POLYMERS, POLYCATIONIC POLYMERS, POLYQUATERNARY AMMONIUM Use SAR for POLYMERS, POLYCATIONIC POLYMERS, POLYPHOSPHONIUM Use SAR for POLYMERS, POLYCATIONIC POLYMERS, POLYSULFONIUM Use SAR for POLYMERS, POLYCATIONIC POLYNUCLEAR AROMATICS Use SAR for NEUTRAL ORGANICS POLYSULFIDES Use SAR for NEUTRAL ORGANICS POTASSIUM No SAR available PRASEODYMIUM No SAR available PROMETHIUM No SAR available PROPARGYL ALCOHOLS Use SAR for ALCOHOLS, PROPARGYL PROPARGYL CARBAMATES No SAR available, excess toxicity 17 PROPARGYLIC ESTERS No SAR available, excess toxicity PROPARGYL HALIDE No SAR available, excess toxicity, PROPARGYL BROMIDE more toxic than PROPARGYL CHLORIDE PROTACTINIUM No SAR available QUATERNARY AMMONIUM SURFACTANTS, DIALKYL Use SAR for SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, DIALKYL QUATERNARY AMMONIUM SURFACTANTS, MONOALKYL Use SAR for SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, MONOALKYL QUINONES No SAR available, para benzoquinone, 5500X excess toxicity to fish RADIUM No SAR available RADON No SAR available RHENIUM No SAR available RHODIUM No SAR available RUBIDIUM No SAR available RUTHENIUM No SAR available SAMARIUM No SAR available SCANDIUM No SAR available SCHIFF BASES Use SAR for SCHIFF BASES, a subclass of AMINES with excess toxicity; (R N= C R) SELENIUM Use SAR for SELENIUM SEMICARBAZIDES, ALKYL SUBSTITUTED Use SAR for SEMICARBAZIDES, ALKYL SUBSTITUTED SEMICARBAZIDES, ARYL META/ PARA SUBSTITUTED Use SAR for SEMICARBAZIDES, ARYL, META/ PARA SUBSTITUTED SEMICARBAZIDES ARYL ORTHO SUBSTITUTED Use SAR for SEMICARBAZIDES, ARYL, ORTHO SUBSTITUTED SEMICARBAZIDES Use SAR for HYDRAZINES SEMICARBAZONES Use SAR for HYDRAZINES SILANES, ALKOXY RSi( OR)( OR)( OR) and CHLOROSILANES reactive with water (hydrolyses) and generally shows low toxicity towards fish, moderate toxicity towards daphnids, and high toxicity towards green algae; the hydrolysis products (silic acids and silanols) probably overchelate nutrient elements and inhibit the growth of algae; all SARs for silanes have to be based on Kows which have C substituted for Si. SILICON No SAR available SILVER Use SAR for SILVER SODIUM No SAR available STRONTIUM No SAR available SULFIDES Use SAR for NEUTRAL ORGANICS SULFIDES (C S C), DISULFIDES (C S S C), and POLYSULFIDES Use SAR for NEUTRAL ORGANICS SULFONATES, ALKYL BENZENE Use SAR for SURFACTANTS, ANIONIC SULFONATES, ALKYL Use SAR for SURFACTANTS, ANIONIC 18 SULFONATES, METHANE Use SAR for ESTERS SULFONIUM Use SAR for SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, if a surfactant; if not a surfactant, Use nearest analog: PHOSPHONIUM or QUATERNARY AMMONIUM analogs are acceptable. SULFUR No SAR available SULFONATES, LINEAR ALKYL Use SAR for SURFACTANTS, ANIONIC SULFONYL CHLORIDES No SAR available, excess toxicity (RS(= O)(= O) Cl) SURFACTANTS, ALCOHOL ETHOXYLATE Use SAR for SURFACTANTS, NONIONIC SURFACTANTS, ALKYL ETHOXYLATE Use SAR for SURFACTANTS, NONIONIC SURFACTANTS, AMPHOTERIC Use SAR for SURFACTANTS, ANIONIC SURFACTANTS, ANIONIC Use SAR for SURFACTANTS, ANIONIC SURFACTANTS, ANIONIC, CARBOXYLIC ACID No SAR available SURFACTANTS, ANIONIC, ALKYL BENZENE SULFONATE Use SAR for SURFACTANTS, ANIONIC SURFACTANTS, ANIONIC, ALKYL SULFONATE Use SAR for SURFACTANTS, ANIONIC ,calculate Kow of alkyl, convert to equivalent alkyl benzene based on equivalent Kow and use SAR for SURFACTANTS, ANIONIC SURFACTANTS, ANIONIC, PHOSPHATE Use SAR for SURFACTANTS, ANIONIC SURFACTANTS, ANIONIC, ALKYL ETHOXYLATE SULFONATE Use SAR for SURFACTANTS, ANIONIC to predict toxicity of alkyl sulfonate and then adjust toxicity depending on number of ethoxylates SURFACTANTS, ANIONIC, ALKYL( SULFONATE and CARBOXYLIC ACID) No SAR available; predict toxicity of alkyl sulfonate and divide effective concentration by 10 times SURFACTANTS, ANIONIC, TWEEN TYPE No SAR available, Use nearest analog SURFACTANTS, CATIONIC, ALKYL NITROGEN ETHOXYLATES Use SAR for SURFACTANTS, ETHOMEEN ETHOMEEN Use SAR for SURFACTANTS, ETHOMEEN SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM DIALKYL Use SAR for SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, DIALKYL, with two large alkyl chains SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, MONOALKYL Use SAR for SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, MONOALKYL, with one large alkyl chain SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, N ETHOXYLATED Use SAR for SURFACTANTS, CATIONIC QUATERNARY AMMONIUM, MONOALKYL, if ethoxy 19 groups are less than five. If ethoxylates are greater than five, Use SAR for SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM MONOALKYL and then reduce toxicity due to the presence of the ethoxylates through the use of the SAR for SURFACTANTS, NONIONIC. SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM TRIALKYL Use SAR for SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, MONOALKYL, three large alkyls, SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, TETRAALKYL Use SAR for SURFACTANTS, CATIONIC, QUATERNARY AMMONIUM, MONOALKYL, four large alkyls SURFACTANTS, NONIONIC SURFACTANTS, ETHOMEEN Use SAR for SURFACTANTS, ETHOMEEN SURFACTANTS, LINEAR ALKYL BENZENE SULFONATES Use SAR for SURFACTANTS, ANIONIC SURFACTANTS, NONIONIC Use SAR for SURFACTANTS, NONIONIC SURFACTANT, NONIONIC, ALKYL ETHOXYLATES Use SAR for SURFACTANTS, NONIONIC SURFACTANT, NONIONIC, ALKYL ETHOXYLATE ALKYL No SAR available, use nearest analog SURFACTANT, NONIONIC, TWEEN TYPE No SAR available, Use nearest analog SULFONATES, LINEAR ALKYL BENZENE Use SAR for SURFACTANTS, ANIONIC TANTALUM No SAR available TECHNIUM No SAR available TELLURIUM No SAR available TERBIUM No SAR available TERPENES Use SAR for NEUTRAL ORGANICS THALLIUM Use SAR for THALLIUM THIAZOLINONES, ISO Use SAR for THIAZOLINONES, ISO THIOLS (MERCAPTANS) Use SAR for THIOLS THIOHYDRAZIDES Use SAR for HYDRAZINES THIOSEMICARBAZIDES Use SAR for HYDRAZINES THIOSEMICARBAZONES Use SAR for HYDRAZINES THORIUM No SAR available THULIUM No SAR available TIN No SAR available for inorganic tins or organotins, Use nearest analog TITANIUM Use SAR for TITANIUM TRIAZIDES, BENZO, N ALKYL SUBSTITUTED Use SAR for NEUTRAL ORGANICS TRIAZINES, SUBSTITUTED See SAR for TRIAZINES, SUBSTITUTED TRIAZOLES No SAR available, excess toxicity, Use nearest analogs TRIAZOLES, AMINO Use SAR for NEUTRAL ORGANICS, herbicide, excess toxicity, TRIAZOLES, BENZO Use SAR for BENZOTRIAZOLES TUNGSTEN Use SAR for TUNGSTEN 20 VANADIUM Use SAR for VANADIUM URANIUM No SAR available UREAS, CYCLIC Use SAR for NEUTRAL ORGANICS UREAS, SUBSTITUTED Use SAR for UREAS, SUBSTITUTED for green algae; to predict toxicity to fish and aquatic invertebrates, Use SAR for NEUTRAL ORGANICS VINYL AMIDES No SAR available VINYL ESTERS No SAR available VINYL NITROS No SAR available, á nitro styrene, excess toxicity, (R C= C= N(= O)(= O)) VINYL SULFONE No SAR available, e. g., divinyl sulfone, excess toxicity, (C= C S(= O)(= O) R) XENON No SAR available YTTERBIUM No SAR available YTTRIUM No SAR available ZINC Use SAR for ZINC ZIRONIUM Use SAR for ZIRCONIUM 21 CHEMICAL CLASSES AND THEIR STRUCTURE ACTIVITY RELATIONSHIPS 22 ACID CHLORIDES 9/ 1993 23 SAR ACID CHLORIDES Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 0.565  0.613 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 the toxicity of acid chlorides.

Limitations: If the log Kow value is greater than 8.0, or if the compound is solid and the LC50 exceeds the water solubility.

References: Curtis MW, Copeland TL, and Ward CH. 1978. Aquatic toxicity of substances proposed for spill prevention regulation. Proc. Natl. Conf. Control of Hazardous Material Spills, Miami Beach, FL. p. 93 103.

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

LIST OF ACID CHLORIDES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Benzoyl chloride 34.7 1.9 C1 Benzoyl chloride 34.1 1.9 C2 ____________________________________________________________________________________ ____ C1 = Curtis et al (1978) C2 = Curtis et al (1981) ACID CHLORIDES 9/ 1993 24 ALCOHOL, PROPARGYL 9/ 1993 25 SAR ALCOHOLS, PROPARGYL Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 0.056  0.511 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 propargyl alcohols.

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 duration.

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

LIST OF PROPARGYL ALCOHOLS USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Chemical identity CBI 310.0 0.4 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991); chemical identity is Confidential Business Information under TSCA. ALCOHOL, PROPARGYL 9/ 1993 26 ACRYLATES 7/ 1988 27 SAR ACRYLATES Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 1.46  0.18 log Kow Statistics: N = 10; R 2 = 0.627 Maximum Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate the toxicity of acrylates and polyacrylates. Allyl acrylate is expected to be about 30 times more toxic than predicted by this SAR.

Limitations: References: Nabholz JV and Platz RD. 1987. Environmental effects of acrylates and methacrylates. I. Category Program Support Document  Generic SNUR and II. Generic Environmental Hazard Assessment (Addendum to Standard Review of PMN 87 930/ 931). Washington, DC: Environmental Effects Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency 20460 0001.

United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, USEPA. ACRYLATES 7/ 1988 28 LIST OF ACRYLATES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 2 Hydroxyethyl acrylate 4.8 0.058 EPA 2 Hydroxypropyl acrylate 3.61 0.251 EPA 2 Hydroxypropyl acrylate 3.26 0.251 EPA 2 Hydroxypropyl acrylate 3.10 0.251 EPA Chemical identity CBI 13.0 1.6 EPA Isobutyl acrylate 2.110 2.204 EPA Isobutyl acrylate 2.090 2.204 EPA Cyclohexyl acrylate 1.48 2.778 EPA Hexyl acrylate 1.14 3.392 EPA Hexyl acrylate 1.09 3.392 EPA Lauryl acrylate * 6.566 EPA ____________________________________________________________________________________ ____

* No mortalities within 96 hours at saturation.

EPA = USEPA (1991); chemical identity is Confidential Business Information under TSCA. ACRYLATES 7/ 1988 29 SAR ACRYLATES Organism: Daphnid Duration: 48 h Endpoint: LC50 Equation: Log LC50 (mM/ L) = 0.009  0.511 log Kow Statistics: N = 2; R 2 = 1.0 Maximum Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for acrylates.

Limitations: References: Beach SA. 1990. Acute toxicity of isooctyl acrylate to Daphnia magna. St Paul, MN: 3M Environmental Laboratory, 3M Company; Toxicity Test Report.

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

LIST OF ACRYLATES USED TO DEVELOP THE DAPHNID LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Chemical identity CBI 59.0 0.78 EPA Isooctyl acrylate 1.2 4.3 B ____________________________________________________________________________________ ____

B = Beach (1990) EPA = USEPA (1991); Chemical identity is Confidential Business Information under TSCA. ACRYLATES 7/ 1988 30 ACRYLATES 7/ 1988 31 SAR ACRYLATES Organism: Green Algae Duration: 96 h Endpoint: EC50 (Growth)

Equation: Log EC50 (mM/ L) = 1.02  0.49 log Kow Statistics: N = 3; R 2 = 0.91 Maximum log Kow : 6.4 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for acrylates.

Limitations: 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.

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

LIST OF ACRYLATES USED TO DEVELOP THE SAR. ____________________________________________________________________________________ ____ 96 h EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Chemical identity CBI 2.2 0.78 EPA Chemical identity CBI 18.5 1.6 EPA ____________________________________________________________________________________ ____

EPA = U. S. EPA (1991); Chemical identities are Confidential Business Information under TSCA. ACRYLATES 7/ 1988 32 ACRYLATES 7/ 1988 33 SAR ACRYLATES Organism: Fish Duration: 32 d Endpoint: Chronic Value (Survival/ Growth)

Equation: Log ChV (mM/ L) = 1.99  0.526 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 acrylates.

Limitations: If the ChV is greater than water solubility or the log Kow 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 ACRYLATES USED TO DEVELOP THE FISH CHRONIC VALUE (ChV) SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 2 Hydroxyethyl acrylate 1.33 0.1 D ____________________________________________________________________________________ ____

D = USEPA (1991) ACRYLATES 7/ 1988 34 ACRYLATES, METHACRYLATES 9/ 1993 35 SAR ACRYLATES, METHACRYLATES Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 0.552  0.715 log Kow Statistics: N = 19; R 2 = 0.774 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate the toxicity of methacrylates and polyacrylates. Allyl methacrylate is about 35 times more toxic than predicted by this SAR.

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: Nabholz JV and Platz RD. 1987. Environmental effects of acrylates and methacrylates. I. Category Program Support Document  Generic SNUR and II. Generic Environmental Hazard Assessment (Addendum to Standard Review of PMN 87 930/ 931). Washington, DC: Environmental Effects Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency 20460 0001.

United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, USEPA. ACRYLATES, METHACRYLATES 9/ 1993 36 LIST OF METHACRYLATES 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 Hydroxyethyl methacrylate 227.0 0.251 EPA Methylmethacrylate 151.0 1.056 EPA Tetrahydrofurfuryl 34.7 1.297 EPA 2 Ethoxyethyl methacrylate 27.7 1.402 EPA 3( Trimethoxysilyl) propyl 175.0 1.464 EPA Allyl methacrylate 0.99 1.570 EPA Chemical identity CBI 34.0 1.774 EPA Chemical identity CBI 32.0 1.774 EPA Isopropyl methacrylate 38.0 1.894 EPA Benzyl methacrylate 4.67 2.824 EPA ____________________________________________________________________________________ ____ EPA = USEPA (1991); chemical identity is Confidential Business Information under TSCA. ALDEHYDES 7/ 1988 37 SAR ALDEHYDES Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 0.449 log Kow  0.314 Statistics: N = 54; R 2 = 0.527 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate the toxicity of aldehydes. Acrolein is about 1400 times more toxic than predicted by this SAR.

Limitations:

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

Geiger DL, Northcott CE, Call DJ, and Brooke LT. 1985. Acute toxicity of organic chemicals to fathead minnows (Pimephales promelas). Volume II. Center for Lake Superior Environmental Studies, University of Wisconsin  Superior. Superior, Wisconsin.

Geiger DL, Poirier SH, Brooke LT, and Call DJ. 1986. Acute toxicity of organic chemicals to fathead minnows (Pimephales promelas). Volume III Center for Lake Superior Environmental Studies, University of Wisconsin  Superior. Superior, Wisconsin.

United States Environmental Protection Agency (USEPA). 1991. Fish acute toxicity databae. Duluth, MN: Environmental Research Laboratory (ERL), Office of Research and Development, USEPA. 6201 congdon Blvd, 55804; contact C. L. Russom (218) 720 5500. ALDEHYDES 7/ 1988 38 LIST OF ALDEHYDES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Ethanal 30.800 0.22 EPA Butanal #1 19.000 0.88 EPA Butanal #2 16.000 0.88 EPA Butanal #3 13.400 0.88 EPA 2 Methylbutyraldehyde 9.970 1.14 EPA Vanillin #2 123.000 1.21 EPA Vanillin #1 57.000 1.21 EPA Isovaleraldehyde 3.250 1.23 EPA Valeraldehyde #1 12.400 1.36 EPA Valeraldehyde #2 13.400 1.37 EPA o Vanillin #1 2.600 1.37 EPA o Vanillin #2 2.200 1.37 EPA 2,4,5 Trimethoxybenzaldehyde 49.500 1.38 EPA Benzaldehyde #2 12.800 1.48 EPA Benzaldehyde #1 7.610 1.48 EPA 4 Nitrobenzaldehyde 10.100 1.50 EPA 5 Hydroxy 2 nitrobenzaldehyde 41.900 1.65 EPA 2 Methylvaleraldehyde 18.800 1.67 EPA 2,4 Dihydroxybenzaldehyde 13.100 1.71 EPA o Nitrobenzaldehyde #1 12.500 1.74 EPA o Nitrobenzaldehyde #2 16.600 1.74 EPA o Fluorobenzaldehyde 1.350 1.76 EPA Hexanal #1 22.000 1.78 EPA Hexanal #2 14.000 1.78 EPA p Dimethylaminobenzaldehyde 45.700 1.81 EPA Salicylaldehyde 2.300 1.81 EPA 3 Ethoxy 4 hydroxybenzaldehyde 87.600 1.88 EPA 5 Bromo 2 nitrovanillin 73.300 1.88 EPA 2,4 Dimethoxybenzaldehyde 20.100 1.91 EPA 2,3 Dimethylvaleraldehyde 16.000 2.07 EPA 5 Bromovanillin 59.700 2.09 EPA 4 Chlorobenzaldehyde 2.200 2.10 EPA o Tolualdehyde 52.900 2.26 EPA 2 Chloro 5 nitrobenzaldehyde #1 3.800 2.28 EPA 2 Chloro 5 nitrobenzaldehyde #2 3.950 2.28 EPA p Ethoxybenzaldehyde 28.100 2.31 EPA 4,6 Dimethoxy 2 hydroxy benzaldehyde 2.680 2.33 EPA Pentafluorobenzaldehyde 1.100 2.45 EPA á, á, á Trifluoro m tolualdehyde #3 1.130 2.47 EPA á, á, á Trifluoro m tolualdehyde #2 0.760 2.47 EPA á, á, á Trifluoro m tolualdehyde #1 0.920 2.47 EPA_ ALDEHYDES 7/ 1988 39 Continued. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 2 Chloro 6 fluorobenzaldehyde 9.410 2.54 EPA 4( Diethylamino) benzaldehyde 23.900 2.94 EPA 5 Chlorosalicylaldehyde 0.770 3.00 EPA p Isopropyl benzaldehyde 6.620 3.07 EPA 2,4 Dichlorobenzaldehyde 1.800 3.11 EPA 5 Bromosalicylaldehyde 1.300 3.15 EPA 4( Diethylamino) salicylaldehyde 5.360 3.34 EPA 3,5 Dibromosalicylaldehyde 0.850 3.83 EPA p Phenoxybenzaldehyde 4.600 3.96 EPA 4( Hexyloxy) m anisaldehyde 2.670 3.99 EPA 3( 3,4 Dichlorophenoxy) benzaldehyde 0.300 5.49 EPA 3( 4 Tert butylphenoxy) benzaldehyde 0.370 5.93 EPA Tetradecanal * 6.12 EPA ____________________________________________________________________________________ ____

* No effects at saturation.

EPA = USEPA (1991) ALDEHYDES 7/ 1988 40 ALDEHYDES 7/ 1988 41 SAR ALDEHYDES Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 0.059  0.607 log Kow Statistics: N = 4; R 2 = 1.0 Maximum log Kow : 6.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for aldehydes.

Limitations: References: Sloof 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.

LIST OF ALDEHYDES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Salicylaldehyde 5.4 2.1 S Salicylaldehyde 5.5 2.1 S Salicylaldehyde 5.8 2.1 S ____________________________________________________________________________________ ____ S = Sloof et al (1983) ALDEHYDES 9/ 1993 42 ALDEHYDES 9/ 1993 43 SAR ALDEHYDES Organism: Green Algae Duration: 96 h Endpoint: EC50 (Growth)

Equation: Use green algae 96 h EC50 SAR developed for neutral organics.

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

Limitations: References: See references for neutral organics. ALDEHYDES 9/ 1993 44 ALDEHYDES 9/ 1993 45 SAR ALDEHYDES Organism: Fish Duration: 32 d Endpoint: Chronic Value (Survival/ Growth)

Equation: Log ChV = 0.81  0.68 log Kow Statistics: N = 3; R 2 = 0.97 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for aldehydes.

Limitations: If the log Kow is greater than 8.0, or if 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 ALDEHYDES USED TO DEVELOP THE FISH 32 d Chronic Value (Survival/ Growth) SAR. ____________________________________________________________________________________ ____ 32 d ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ o Tolualdehyde 1.61 2.1 D á, á, á Trifluoro m tolualdehyde 0.19 2.6 D ____________________________________________________________________________________ ____

D = USEPA (1991) ALDEHYDES 9/ 1993 46 ALDEHYDES 9/ 1993 47 SAR ALDEHYDES Organism: Green Algae Duration: 96 h Endpoint: Chronic Value (Growth)

Equation: Use the equation for the green algae chronic value SAR developed for neutral organics.

Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: The green algae chronic value SAR for neutral organics may be used to estimate toxicity for aldehydes.

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

References: Sloof 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. ALDEHYDES 9/ 1993 48 AMINES, ALIPHATICC 9/ 1993 49 SAR AMINES, ALIPHATIC Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 0.72  0.64 log Kow Statistics: N = 55; R 2 = 0.82 Maximum log Kow : 6.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate the toxicity of aliphatic amines.

Limitations: If the log Kow value is greater than 6.0, no effects expected in a saturated solution.

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

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

Calamari D, DaGasso R, Galassi S, Provini A, and Vighi M. 1980. Biodegradation and toxicity of selected amines on aquatic organisms. Chemosphere 9: 753 762.

Geiger DL, Piorier SH, Brooke LT, and Call DJ (eds). 1986. Acute toxicities of organic chemicals to fathead minnows (Pimephales promelas). Superior, WI: Center for Lake Superior Environmental Studies, University of Wisconsin Superior. Volume III.

Geiger DL, Call DJ, and Brooke LT (eds). 1988. Acute toxicities of organic chemicals to fathead minnows (Pimephales promelas). Superior, WI: Center for Lake Superior Environmental Studies, University of Wisconsin Superior. Volume IV.

Platz RD and Nabholz JV. 1990. Generic environmental hazard assessment of aliphatic amines. Washington, DC: Environmental Effects Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency. Unpublished manuscript. AMINES, ALIPHATIC 9/ 1993 50 United States Environmental Protection Agency (USEPA). 1990. Summary of structure activity data files: University of Wisconsin Superior (UWS) and Environmental Research Laboratory, Duluth, MN (ERL D) research team. Computer printout from Environmental Effects Branch, HERD, USEPA, Washington, DC.

United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, United States Environmental Protection Agency. AMINES, ALIPHATICC 9/ 1993 51 LIST OF ALIPHATIC AMINES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Triethanolamine 1180.000 1.59 EPA1 1,3 Diaminopropane 1190.000 1.49 BR Diethanolamine 47100.000 1.46 EPA1 Ethanolamine 2070.000 1.30 EPA1 Ethylenediamine 220.000 1.22 EPA1 1,2 Diaminopropane 1010.000 0.91 BR Morpholine 380.000 0.72 C 2 Methoxyethylamine 524.000 0.67 BR Dimethylamine 118.000 0.52 C 2( Ethylamino) ethanol 1480.000 0.46 BR Allylamine 27.000 0.15 B Ethylamine 227.000 0.14 EPA1 N( 3 Methoxypropyl) 3,4,5 trimethoxybenzylamine 136.000 0.09 EPA1 5 Diethylamino 2 pentanone 336.000 0.35 G1 Propylamine 308.000 0.39 BR N, N Diethylethanolamine 1780.000 0.40 G1 Diallylamine 20.000 0.51 B Diethylamine 855.000 0.54 BR Diethylamine 182.000 0.54 C tert Butylamine 270.000 0.57 C 3 Dimethylaminopropyl chloride hydrochloride 133.000 0.66 G1 sec Butylamine 275.000 0.70 EPA1 2( Diisopropylamino) ethanol 201.000 0.86 G2 n Butylamine 268.000 0.92 G1 Benzylamine 102.000 1.09 EPA1 1,2 Dimethylpropylamine 284.000 1.10 G1 Diisopropylamine 196.000 1.16 C 2,2 Dimethyl 1 propylamine 475.000 1.19 G1 1,8 Diamino p menthane 65.300 1.23 G2 Tripropargylamine 296.000 1.26 G1 Cyclohexylamine 90.000 1.37 C N, N bis( 2,2 Diethoxyethyl) methylamine 634.000 1.39 G1 N, N bis( 2,2 Diethoxyethyl) methylamine 637.000 1.39 G1 Amylamine 177.000 1.45 G1 3,3 Dimethylbutylamine 602.000 1.72 G2 Chemical Identity CBI 778.000 1.93 EPA N, N Dimethylbenzylamine 37.800 1.98 EPA1 Hexylamine 56.600 1.98 G1 ____________________________________________________________________________________ ____ AMINES, ALIPHATIC 9/ 1993 52 Continued. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____

1 Adamantylamine 25.000 2.00 G1 N Ethylbenzylamine 57.100 2.04 EPA1 tert Octylamine 24.600 2.43 G2 Heptylamine 21.800 2.51 BR Dibutylamine 37.000 2.66 C Tripropylamine 50.900 2.82 G1 1 Methylheptylamine 5.110 2.82 BR 1 Methylheptylamine 5.280 2.82 BR N, N Diethylcyclohexylamine 21.400 2.98 G2 Octylamine 5.190 3.04 G2 Nonylamine 2.160 3.57 EPA1 Chemical identity CBI 2.800 4.10 EPA Decylamine 1.030 4.10 EPA1 Undecylamine 0.210 4.63 EPA1 Dihexylamine 0.780 4.77 BR Dodecylamine 0.103 5.16 EPA1 Tridecylamine 0.065 5.68 EPA1 ____________________________________________________________________________________ ____

EPA = USEPA (1991); Chemical identity is Confidential Business Information under TSCA. EPA1 = USEPA (1990) BR = Brooke et al (1984) B = Bridie et al (1979) C = Calamari et al (1980) G1 = Geiger et al (1986) G2 = Geiger et al (1988) AMINES, ALIPHATIC 53 SAR AMINES, ALIPHATIC Organism: Daphnids Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 0.524  0.584 log Kow Statistics: N = 10; R 2 = 0.78 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate the toxicity of aliphatic amines.

Limitations: If the log Kow value is greater than 5.0, no effects expected in a saturated solution.

References: Cowgill UM, Takahashi IT, and Applegath SL. 1985. A comparison of the effect of four benchmark chemicals on Daphnia magna and Ceriodaphnia dubia/ affinis tested at two different temperatures.

Gersich FM, Milazzo DP, and Voos Esquivel C. 1988. An invertebrate life cycle study of the toxicity of Daphnia magna Straus. Mammalian and Environmental Toxicology Research Laboratory. Dow Chemical Company. Study ID: ES DR 0065 5425 6.

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

Platz RD and Nabholz JV. 1990. Generic environmental hazard assessment of aliphatic amines. Washington, DC: Environmental Effects Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency. Unpublished manuscript.

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

Van Leeuwen CJ, Maas Diepeveen JL, Niebeek G, Vergouw WHA, Griffioen PS, and Luijken MW. 1985. Aquatic toxicological aspects of dithiocarbamates and related compounds. I. Short term toxicity tests. Aquatic Toxicology 7: 145 164. AMINES, ALIPHATIC 54 LIST OF ALIPHATIC AMINES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____

Diethanolamine 131.000 1.46 C Diethanolamine 55.000 1.46 L Ethylenediamine 26.500 1.22 VL Chemical identity CBI 1760.000 0.90 EPA Dimethylamine 50.000 0.52 VL Chemical identity CBI 4.300 0.44 EPA Diethylamine 56.000 0.54 VL Chemical identity CBI 15.000 1.03 EPA Chemical identity CBI 3.800 2.74 EPA 2( Decylthio) ethylamine hydrochloride 0.033 4.85 G ____________________________________________________________________________________ ____

C = Cowgill et al (1985) EPA = USEPA (1991); Chemical identity is Confidential Business Information under TSCA. G = Gersich et al (1988) L = LeBlanc (1980) VL = Van Leeuwen et al (1985) AMINES, ALIPHATIC 55 SAR AMINES, ALIPHATIC Organism: Green Algae Duration: 96 h Endpoint: EC50 (Growth)

Equation: Log 96 h EC50 (mM/ L) = 0.548  0.434 log Kow Statistics: N = 14; R 2 = 0.74 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for aliphatic amines.

Limitations: If the log Kow value is greater than 7.0, no effects expected in a saturated solution.

References: Calamari D, DaGasso R, Galassi S, Provini A, and Vighi M. 1980. Biodegradation and toxicity of selected amines on aquatic organisms. Chemosphere 9: 753 762.

Platz RD and Nabholz JV. 1990. Generic environmental hazard assessment of aliphatic amines. Washington, DC: Environmental Effects Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency. Unpublished manuscript.

United States Environmental Protection Agency (USEPA). 1990. Summary of structure activity data files: University of Wisconsin Superior (UWS) and Environmental Research Laboratory, Duluth, MN (ERL D) research team. Computer printout from Environmental Effects Branch, HERD, USEPA, Washington, DC.

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

Van Leeuwen CJ, Maas Diepeveen JL, Niebeek G, Vergouw WHA, Griffioen PS, and Luijken MW. 1985. Aquatic toxicological aspects of dithiocarbamates and related compounds. I. Short term toxicity tests. Aquatic Toxicology 7: 145 164. AMINES, ALIPHATIC 56 LIST OF ALIPHATIC AMINES USED TO DEVELOP THE ALGAL 96 h EC50 SAR. ____________________________________________________________________________________ ____ 96 h EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____

Ethylenediamine 61.000 1.22 VL Morpholine 28.000 0.72 C Dimethylamine 30.000 0.52 VL Dimethylamine 9.000 0.52 C Diethylamine 20.000 0.54 C Diethylamine 56.000 0.54 VL tert Butylamine 16.000 0.57 C Chemical identity CBI 1.800 1.03 EPA Diisopropylamine 20.000 1.16 C Cyclohexylamine 20.000 1.37 C Dibutylamine 19.000 2.66 C Chemical identity CBI 1.040 2.74 EPA Octylamine 0.220 3.04 EPA1 Chemical identity CBI 0.130 6.85 EPA ____________________________________________________________________________________ ____

C = Calamari et al (1980) EPA1 = USEPA (1990) EPA = USEPA (1991); Chemical identity is Confidential Business Information under TSCA. VL = Van Leeuwen et al (1985) AMINES, ALIPHATIC 57 SAR AMINES, ALIPHATIC Organism: Green Algae Duration: Endpoint: Chronic Value (Growth)

Equation: Log ChV (mM/ L) = 1.399  0.334 log Kow Statistics: N = 11; R 2 = 0.61 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for aliphatic amines.

Limitations: If the log Kow value is greater than 7.0, no effects expected at saturation.

References: Calamari D, DaGasso R, Galassi S, Provini A, and Vighi M. 1980. Biodegradation and toxicity of selected amines on aquatic organisms. Chemosphere 9: 753 762.

Platz RD and Nabholz JV. 1990. Generic environmental hazard assessment of aliphatic amines. Washington, DC: Environmental Effects Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency. Unpublished manuscript.

United States Environmental Protection Agency (USEPA). 1989. Report on alga toxicity tests on selected OTS chemicals. Unpublished preliminary draft. Corvallis Environmental Research Laboratory. Corvallis, OR: United States Environmental Protection Agency.

United States Environmental Protection Agency (USEPA). 1991. OTS PMN ECOTOX. Washington, DC: Office of Toxic Substances, United States Environmental Protection Agency. AMINES, ALIPHATIC 58 LIST OF ALIPHATIC AMINES USED TO DEVELOP THE ALGAL ChV SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____

Morpholine 1.000 0.72 C Dimethylamine 2.000 0.52 C Diethylamine 2.000 0.54 C tert Butylamine 2.000 0.57 C Chemical identity CBI 0.110 1.03 EPA2 Diisopropylamine 5.000 1.16 C Cyclohexylamine 5.000 1.37 C Dibutylamine 2.500 2.66 C Chemical identity CBI 0.410 2.74 EPA2 Octylamine 0.650 3.04 EPA1 Chemical identity CBI 0.050 6.85 EPA2 ____________________________________________________________________________________ ____

C = Calamari et al (1980) EPA1 = USEPA (1989) EPA2 = USEPA (1991); Chemical identity is Confidential Business Information under TSCA. ANILINES 7/ 1988 59 SAR ANILINES Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 0.956  0.739 log Kow Statistics: N = 20; R 2 = 0.882 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for anilines.

Limitations: Di and tri nitroanilines are more toxic than predicted; a fish 96 h LC50 SAR has been developed for dinitroanilines.

2,3,5,6 Tetrachloroaniline is 19 times more toxic than predicted by this SAR. Tetrabromoaniline may be more toxic than predicted by this SAR as well.

N substituted anilines are less toxic than predicted by this SAR; for these compounds use the neutral organics fish 96 h LC50 SAR.

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. ANILINES 7/ 1988 60 LIST OF ANILINES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____

ANILINES USED IN CALCULATION OF THIS SAR aniline 134.0 0.9 VB 4 nitroaniline 125.0 1.3 VB 4 toluidine 149.0 1.4 VB 4 chloroaniline 32.5 1.8 VB 4 ethylaniline 73.0 2.0 VB pentafluoroaniline 37.1 2.2 VB 2 chloro 4 nitroaniline 20.2 2.2 VB 4 bromoaniline 47.5 2.3 VB 4 ethoxy 2 nitroaniline 26.0 2.5 VB á, á, á 4 tetrafluoro 2 toluidine 29.6 2.6 VB á, á, á 4 tetrafluoro 3 toluidine 30.1 2.6 VB 3,4 dichloroaniline 7.6 2.7 VB 3 benzyloxyaniline 9.14 2.8 VB 4 butylaniline 10.2 3.2 VB 2,3,6 trichloroaniline 3.64 3.3 VB 4 hexyloxyaniline 3.2 3.7 VB 2,6 diisopropylaniline 15.3 4.1 VB 4 octylaniline 0.120 5.3 VB 4 decylaniline 0.062 6.3 VB 4 dodecyl aniline .* 7.4 VB ANILINES WITH EXCESS TOXICITY 2,3,5,6 tetrachloroaniline 0.270 4.1 VB ____________________________________________________________________________________ ____

* No fish mortality in saturated solutions.

VB = Veith and Broderius (1987) ANILINES 9/ 1993 61 SAR ANILINES Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 1.623  0.271 log Kow Statistics: N = 24; R 2 = 0.24 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for anilines.

Limitations: Di and tri nitroanilines are more toxic than predicted by this SAR; a daphnid 48 h LC50 SAR has been developed for dinitroanilines.

Tetrachloro and tetrabromo aniline may be 20 times more toxic than predicted by this SAR.

N substituted anilines are less toxic than predicted by this SAR; for these compounds use the neutral organics daphnid 48 h LC50 SAR.

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: Canton JH and Adema DMM. 1978. Reproducibility of short term and reproduction toxicity experiments with Daphnia magna and comparison of the sensitivity of Daphnia magna with Daphnia pulex and Daphnia cucullata in short term experiments. Hydrobiologia 2: 135 140.

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.

Sloof 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. ANILINES 9/ 1993 62 LIST OF ANILINES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ p aminophenol 0.240 0.2 K m aminophenol 1.1 0.2 K aniline 0.640 0.6 S benzidine (dianiline) 0.600 1.6 K 4 aminoacetophenone 5.0 0.9 K aniline 0.300 0.9 K aniline 0.100 0.9 CA aniline 0.680 0.9 CA p methoxyaniline 1.9 1.0 K 2 amino 4 methoxyphenol 3.0 1.3 K 5 chloro 2,4 dimethoxyaniline 1.62 1.8 K p chloroaniline 0.310 1.9 K m chloroaniline 0.350 1.9 K o chloroaniline 1.8 1.9 K p ethylaniline 2.0 2.1 K o bromoaniline 3.0 2.1 K o ethylaniline 14.0 2.1 K 2,4 dimethylaniline 9.9 2.2 K 3 trifluoromethylaniline 2.7 2.3 K 4 chloro 2 nitroaniline 3.2 2.6 K 3 chloro 4 methylaniline 0.620 2.6 K 2,6 dichloroaniline 1.4 2.8 K 2,4 dichloroaniline 2.7 2.8 K ____________________________________________________________________________________ ____

K = Kuhn et al (1989) S = Sloof et al (1983) CA = Canton and Adema (1978) ANILINES 9/ 1993 63 SAR ANILINES Organism: Fish Duration: 32 d Endpoint: Chronic Value (Survival/ Growth)

Equation: Log ChV (mM/ L) = 1.516  0.625 log Kow Statistics: N = 11; R 2 = 0.66 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for anilines.

Limitations: N substituted anilines are less toxic than predicted by this SAR; for these compounds use the neutral organics fish ChV SAR.

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: Bresch H, Beck H, Ehlermann D, Schlaszus H and Urbanek M. 1990. A long term toxicity test comprising reproduction and growth of zebrafish with 4 chloroaniline. Archives of Environmental Contamination and Chemistry 19: 419 427.

Call DJ, Poirier SH, Knuth ML, Harting SL and Lindbery CA. 1987. Toxicity of 3,4 dichloroaniline to fathead minnow, Pimephales promelas, in acute and early life stage exposures. Bulletin of Environmental Contamination and Toxicology 38: 352 358.

United States Environmental Protection Agency (USEPA). 1990. Rainbow trout early life stage toxicity test with 2,6 dichloro 4 nitrobenzeneamine. TSCA Section 4 Test Report. Washington, DC: Office of Toxic Substances, USEPA.

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.

Van Leeuwen CJ, Adema DMM and Hermens J. 1990. Quantitative structure activity relationships for fish early life stage toxicity. Aquatic Toxicology 16: 321 334. ANILINES 9/ 1993 64 LIST OF ANILINES USED TO DEVELOP THE FISH CHRONIC VALUE (ChV) SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ aniline 1.8 0.9 VL aniline 0.569 0.9 D 4 chloroaniline 0.400 1.8 B 3 chloroaniline 1.0 1.9 VL 3,4 dichloroaniline 0.020 2.7 C 3,4 dichloroaniline 0.006 2.7 C 3,5 dichloroaniline 0.320 2.9 VL 2,6 dichloro 4 nitroaniline 0.016 3.0 EPA 2,4,5 trichloroaniline 0.056 3.7 VL 2,3,4,5 tetrachloroaniline 0.032 4.6 VL pentachloroaniline 0.010 5.1 VL ____________________________________________________________________________________ ____

EPA = USEPA (1990) C = Call et al (1987) D = USEPA (1991) VL = Van Leeuwen et al (1990) B = Bresch et al (1990) ANILINES 9/ 1993 65 SAR ANILINES Organism: Daphnid Duration: 16 d Endpoint: Chronic Value (Survival/ Reproduction)

Equation: Log ChV (mM/ L) = 3.12  0.36 log Kow Statistics: N = 3;; R 2 = 0.98 Maximum log Kow : 9.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for anilines.

Limitations: N substituted anilines are less toxic than predicted by this SAR; for these compounds use the daphnid ChV SAR for neutral organics.

If the log Kow value is greater than 9.0, 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). 1990. Daphnid Chronic Toxicity Tests with aniline and 2 chloroaniline. TSCA Sec. 4 Test Reports. Washington, DC: U. S. Environmental Protection Agency, Office of Toxic Substances.

LIST OF ANILINES USED TO DEVELOP THE DAPHNID CHRONIC VALUE (ChV) SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ aniline 0.021 0.9 EPA 2 chloroaniline 0.034 1.9 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1990) ANILINES 9/ 1993 66 ANILINES 9/ 1993 67 SAR ANILINES Organism: Green Algae Duration: Endpoint: Chronic Value (Growth)

Equation: Log ChV (mM/ L) = 0.411  0.588 log Kow Statistics: N = 5; R 2 = 1.0 Maximum log Kow : 9.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for anilines.

Limitations: N substituted anilines are less toxic than predicted by this SAR; for these compounds use the neutral organics green algae ChV SAR.

If the log Kow value is greater than 9.0, or if the compound is solid and the ChV exceeds the water solubility, no effects expected at saturation.

References: Sloof 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.

LIST OF ANILINES USED TO DEVELOP THE GREEN ALGAE CHRONIC VALUE (ChV) SAR. ____________________________________________________________________________________ ____ Log ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ aniline 11.0 0.9 S aniline 8.0 0.9 S aniline 16.0 0.9 S aniline 10.0 0.9 S ____________________________________________________________________________________ ____

S = Slooff et al (1987) ANILINES 9/ 1993 68 ANILINES 9/ 1993 69 SAR ANILINES Organism: Fish Duration: 14 d Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 1.02  0.988 log Kow Statistics: N = 17; R 2 = 0.783 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for the following classes of compounds:

1. Anilines 2. Chloroanilines 3. Alkylanilines 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: Hermans J, Leeuwangh P, and Musch A. 1984. Quantitative structureactivity relationships and mixture toxicity studies of chloro and alkylanilines at an acute lethal toxicity level to the guppy, Poecilia reticulata. Ecotoxicology and Environmental Safety 8: 388 394. ANILINES 9/ 1993 70 LIST OF ANILINES USED TO DEVELOP THE FISH 14 d LC50 SAR. ____________________________________________________________________________________ ____ Log LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Aniline 125.0 1.03 H 2 Methylaniline 81.3 1.54 H 3 Methylaniline 36.3 1.54 H 4 Methylaniline 10.7 1.54 H 2 Chloroaniline 6.2 1.76 H 3 Chloroaniline 13.4 1.76 H 4 Chloroaniline 26.0 1.76 H 2 Ethylaniline 74.7 2.07 H 3 Ethylaniline 27.1 2.07 H 4 Ethylaniline 29.1 2.07 H 2,5 Dichloroaniline 1.65 2.42 H 2,4 Dichloroaniline 6.3 2.42 H 3,5 Dichloroaniline 3.9 2.42 H 3,4 Dichloroaniline 6.3 2.42 H 2,3,4 Trichloroaniline 1.4 3.17 H 2,4,5 Trichloroaniline 2.0 3.17 H 2,3,4,5 Tetrachloroaniline 0.36 3.92 H ____________________________________________________________________________________ ____

H = Hermans et al (1984) AMINO ANILINES, META OR 1,3 SUBSTITUTED 9/ 1993 71 SAR ANILINES, AMINO, META OR 1,3 SUBSTITUTED Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 0.978  0.740 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for meta or 1,3 substituted amino anilines.

Limitations: If the log Kow value is greater than 7.0, no effects expected at saturation. duration.

References: United States Environmental Protection Agency (USEPA). 1991. OTS TSCA Section 4 database. Washington, DC: USEPA, Office of Toxic Substances.

LIST OF META SUBSTITUTED AMINO ANILINES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ m Phenylenediamine 1618 0.3 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991) ANILINES, AMINO, META OR 1,3 SUBSTITUTED 72 SAR ANILINES, AMINO, META OR 1,3 SUBSTITUTED Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 1.44  0.466 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for meta or 1,3 substituted amino anilines.

Limitations: If the log Kow value is greater than 7.0, no effects expected at saturation.

References: United States Environmental Protection Agency (USEPA). 1991. OTS TSCA Section 4 database. Washington, DC: USEPA, Office of Toxic Substances.

LIST OF META SUBSTITUTED AMINO ANILINES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ m Phenylenediamine 5.9 0.3 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991) ANILINES, AMINO, META OR 1,3 SUBSTITUTED 73 ANILINES, AMINO, META OR 1,3 SUBSTITUTED 74 SAR ANILINES, AMINO, META OR 1,3 SUBSTITUTED Organism: Green Algae Duration: 96 h Endpoint: EC50 Equation: Log 96 h EC50 (mM/ L) = 1.8  0.333 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 6.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for meta or 1,3 substituted amino anilines.

Limitations: If the log Kow value is greater than 6.0, no effects expected at saturation.

References: United States Environmental Protection Agency (USEPA). 1991. OTS TSCA Section 4 database. Washington, DC: USEPA, Office of Toxic Substances.

LIST OF META SUBSTITUTED AMINO ANILINES USED TO DEVELOP THE GREEN ALGAE 96 h EC50 SAR. ____________________________________________________________________________________ ____ 96 h EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ m Phenylenediamine 2.4 0.3 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991) ANILINES, AMINO, META OR 1,3 SUBSTITUTED 9/ 1993 75 ANILINES, AMINO, META OR 1,3 SUBSTITUTED 9/ 1993 76 SAR ANILINES, AMINO, META OR 1,3 SUBSTITUTED Organism: Daphnid Duration: 16 d Endpoint: Chronic Value Equation: Log ChV (mM/ L) = 3.29  0.301 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 meta or 1,3 substituted amino anilines.

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 TSCA Section 4 database. Washington, DC: USEPA, Office of Toxic Substances.

LIST OF META SUBSTITUTED AMINO ANILINES USED TO DEVELOP THE DAPHNID ChV SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ m Phenylenediamine 0.070 0.3 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991) ANILINES, AMINO, META OR 1,3 SUBSTITUTED 9/ 1993 77 ANILINES, AMINO, ORTHO OR 1,2 SUBSTITUTED 9/ 1993 78 SAR ANILINES, AMINO, ORTHO OR 1,2 SUBSTITUTED Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 0.547  0.522 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for ortho or 1,2 substituted amino anilines.

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: United States Environmental Protection Agency (USEPA). 1991. OTS TSCA Section 4 database. Washington, DC: USEPA, Office of Toxic Substances.

LIST OF ORTHO SUBSTITUTED AMINO ANILINES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ o Phenylenediamine 44 0.3 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991) ANILINES, AMIN0, ORTHO OR 1,2 SUBSTITUTED 9/ 1993 79 ANILINES, AMINO, ORTHO OR 1,2 SUBSTITUTED 9/ 1993 80 SAR ANILINES, AMINO, ORTHO OR 1,2 SUBSTITUTED Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 2.21  0.356 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for ortho or 1,2 substituted amino anilines.

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: United States Environmental Protection Agency (USEPA). 1991. OTS TSCA Section 4 database. Washington, DC: USEPA, Office of Toxic Substances.

LIST OF ORTHO SUBSTITUTED AMINO ANILINES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ o Phenylenediamine 0.880 0.3 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991) ANILINES, AMINO, ORTHO OR 1,2 SUBSTITUTED 9/ 1993 81 ANILINES, AMINO, ORTHO OR 1,2 SUBSTITUTED 9/ 1993 82 SAR ANILINES, AMINO, ORTHO OR 1,2 SUBSTITUTED Organism: Green Algae Duration: 96 h Endpoint: EC50 Equation: Log 96 h EC50 (mM/ L) = 2.848  0.159 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 6.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for ortho or 1,2 substituted amino anilines.

Limitations: If the log Kow value is greater than 6.0, 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 TSCA Section 4 database. Washington, DC: USEPA, Office of Toxic Substances.

LIST OF ORTHO SUBSTITUTED AMINO ANILINES USED TO DEVELOP THE GREEN ALGAE 96 h EC50 SAR. ____________________________________________________________________________________ ____ 96 h EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ o Phenylenediamine 0.160 0.3 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991) ANILINES, AMINO, ORTHO OR 1,2 SUBSTITUTED 9/ 1993 83 ANILINES, AMINO, PARA OR 1,4 SUBSTITUTED 9/ 1993 84 SAR ANILINES, AMINO, PARA OR 1,4 SUBSTITUTED Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 3.337  0.123 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for para or 1,4 substituted amino anilines.

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: United States Environmental Protection Agency (USEPA). 1991. OTS TSCA Section 4 database. Washington, DC: USEPA, Office of Toxic Substances.

LIST OF PARA SUBSTITUTED AMINO ANILINES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ p Phenylenediamine 0.060 0.3 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991) ANILINES, AMINO, PARA OR 1,4 SUBSTITUTED 9/ 1993 85 ANILINES, AMINO, PARA OR 1,4 SUBSTITUTED 9/ 1993 86 SAR ANILINES, AMINO, PARA OR 1,4 SUBSTITUTED Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 2.686  0.288 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for para or 1,4 substituted amino anilines.

Limitations: If the log Kow is greater than 7.0, 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 Section 4 database. Washington, DC: USEPA, Office of Toxic Substances.

LIST OF PARA SUBSTITUTED AMINO ANILINES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ p Phenylenediamine 0.280 0.3 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991) ANILINES, AMINO, PARA OR 1,4 SUBSTITUTED 9/ 1993 87 ANILINES, AMINO, PARA OR 1,4 SUBSTITUTED 9/ 1993 88 SAR ANILINES, AMINO, PARA OR 1,4 SUBSTITUTED Organism: Green Algae Duration: 96 h Endpoint: EC50 Equation: Log 96 h EC50 (mM/ L) = 2.657  0.190 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 6.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for para or 1,4 substituted amino anilines.

Limitations: If the log Kow value is greater than 6.0, 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 TSCA Section 4 database. Washington, DC: USEPA, Office of Toxic Substances.

LIST OF PARA SUBSTITUTED AMINO ANILINES USED TO DEVELOP THE GREEN ALGAE 96 h EC50 SAR. ____________________________________________________________________________________ ____ 96 h EC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ p Phenylenediamine 0.28 0.3 EPA ____________________________________________________________________________________ ____

EPA = USEPA (1991) ANILINES, DINITRO 9/ 1993 89 SAR ANILINES, DINITRO Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 0.027  0.596 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for dinitroanilines and other polynitroanilines.

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 DINITROANILINES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 hour LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 2,4 dinitroaniline 15.5 1.8 VB ____________________________________________________________________________________ ____

VB = Veith and Broderius (1987) ANILINES, DINITRO 9/ 1993 90 ANILINES, DINITRO 9/ 1993 91 SAR ANILINES, DINITRO Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: log 48 h LC50 (mM/ L) = 0.296  0.558 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for dinitroanilines and other polynitroanilines.

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: 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.

LIST OF DINITROANILINES USED TO DEVELOP THE DAPHNID 48 h LC50. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 2,4 dinitroaniline 9.6 1.8 K ____________________________________________________________________________________ ____

Kuhn = Kuhn et al (1989) ANILINES, DINITRO 9/ 1993 92 ANILINES, DINITRO 9/ 1993 93 SAR ANILINES, DINITRO Organism: Fish Duration: 32 d Endpoint: Chronic Value (Survival/ Growth)

Equation: Log ChV (mM/ L) = 0.91  0.661 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 dinitroanilines and other polynitroanilines.

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 DINITROANILINES USED TO DEVELOP THE FISH CHRONIC (ChV) SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 2,4 dinitroaniline 1.41 1.8 D ____________________________________________________________________________________ ____

D = USEPA (1991) ANILINES, DINITRO 9/ 1993 94 AZIRIDINES 9/ 1993 95 SAR AZIRIDINES Organism: Fish Duration: Acute Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 1.65  0.364 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for aziridines.

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: Juhnke I and Luedemann D. 1978. Results of the investigation of 200 chemical compounds for acute toxicity with the Golden Orfe test. Z. F. Wasser Und Abwasser Forschung 11: 161 164. Translation by SCITRAN (Scientific Translation Service), Santa Barbara, CA 93108.

LIST OF AZIRIDINES USED TO DEVELOP THE FISH ACUTE LC50 SAR. ____________________________________________________________________________________ ____ LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____

Aziridine 2.4 1.1 J ____________________________________________________________________________________ ____

J = Juhnke and Luedemann (1978) AZIRIDINES 9/ 1993 96 AZIRIDINES 9/ 1993 97 SAR AZIRIDINES Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 1.062  0.52 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This equation may be used to estimate toxicity for aziridines.

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: Bringmann G and Kuhn R. 1977. Results of the damaging effect of water pollutants on Daphnia magna. Z. Wasser Abwasser Forsch. 10( 5): 161 166.

LIST OF AZIRIDINES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Aziridine 14.0 1.1 B ____________________________________________________________________________________ ____

B = Bringmann and Kuhn (1977) AZIRIDINES 9/ 1993 98 AZIRIDINES 9/ 1993 99 SAR AZIRIDINES Organism: Green Algae Duration: 7 d Endpoint: Chronic Value Equation: Log ChV (mM/ L) = 2.4  0.33 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 aziridines.

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 Research 14( 3): 231 241.

LIST OF AZIRIDINES USED TO DEVELOP THE GREEN ALGAE CHV SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Aziridine 0.370 1.1 B ____________________________________________________________________________________ ____

B = Bringmann and Kuhn (1980) AZIRIDINES 9/ 1993 100 BENZENES, DINITRO 9/ 1993 101 SAR BENZENES, DINITRO Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log 96 h LC50 (mM/ L) = 1.867  0.333 log Kow Statistics: N = 2; R 2 = 1.0 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for dinitrobenzenes and other polynitrobenzenes.

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.

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

LIST OF DINITROBENZENES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ 96 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 1,3 dinitrobenzene 0.71 1.5 VB Chemical identity CBI 0.013 3.2 EPA ____________________________________________________________________________________ ____

VB = Veith and Broderius (1987) EPA = USEPA (1991); chemical identity is Confidential Business Information under TSCA. BENZENES, DINITRO 9/ 1993 102 BENZENES, DINITRO 9/ 1993 103 SAR BENZENES, DINITRO Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: Log 48 h LC50 (mM/ L) = 0.325  0.634 log Kow Statistics: N = 3; R 2 = 0.86 Maximum log Kow : 7.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for dinitrobenzenes or other polynitrobenzenes.

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 J, 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.

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

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

LIST OF DINITROBENZENES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ 48 h LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 1,3 dinitrobenzene 43.0 1.6 H 2,3 dinitrotoluene 0.66 2.0 LB Chemical identity CBI 0.012 3.2 EPA ____________________________________________________________________________________ ____

LB = LeBlanc (1987) BENZENES, DINITRO 9/ 1993 104 H = Hermens et al (1984) EPA = USEPA (1991); chemical identities are Confidential Business Information under TSCA. BENZENES, DINITRO 9/ 1993 105 SAR BENZENES, DINITRO Organism: Fish Duration: 32 d Endpoint: Chronic Value (Survival/ Growth)

Equation: Log ChV (mM/ L) = 3.0  0.40 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 dinitrobenzenes or other polynitrobenzenes.

Limitations: If the log Kow value is greater than 8.0, or is the compound is solid and the ChV exceeds the water solubility, no effects are 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 DINITROBENZENES USED TO DEVELOP THE FISH CHRONIC VALUE (ChV) SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 1,3 dichloro 4,6 dinitro benzene 0.023 2.5 D ____________________________________________________________________________________ ____

D = USEPA (1991) BENZENES, DINITRO 9/ 1993 106 BENZENES, DINITRO 9/ 1993 107 SAR BENZENES, DINITRO Organism: Daphnid Duration: 16 d Endpoint: Chronic Value (Survival/ Reproduction)

Equation: Log ChV (mM/ L) = 0.7  0.625 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 dinitrobenzenes or other polynitrobenzenes.

Limitations: If the log Kow value is greater than 8.0, or is the compound is solid and the ChV exceeds the water solubility, no effects are 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 DINITROBENZENES USED TO DEVELOP THE DAPHNID CHRONIC VALUE (ChV) SAR. ____________________________________________________________________________________ ____ ChV Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ 1,3 dinitrotoluene 3.2 1.6 H ____________________________________________________________________________________ ____

H = Hermens et al (1984) BENZENES, DINITRO 9/ 1993 108 BENZOTRIAZOLES 7/ 1988 109 SAR BENZOTRIZOLES Organism: Fish Duration: 96 h Endpoint: LC50 (Mortality)

Equation: Log LC50 (mM/ L) = 0.366  0.587 log Kow Statistics: N = 2; R 2 = 1.00 Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate the toxicity of substituted benzotriazoles with substitution on the 5th position. Toxicity estimates for substituted benzotriazoles with substitutions on the triazole ring may not be valid with this SAR.

This SAR may be used for substituted benzotriazoles with substitutions on the 3rd, 4th or 6th positions (other benzo positions).

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: Nabholz JV. 1987. Generic review of various benzotriazoles. Washington, DC: Environmental Effects Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency.

LIST OF BENZOTRIAZOLES USED TO DEVELOP THE FISH 96 h LC50 SAR. ____________________________________________________________________________________ ____ LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Benzotriazole 39.0 1.45 N 5 Butylbenzotriazole 2.8 3.68 N ____________________________________________________________________________________ ____

N = Nabholz (1987). BENZOTRIAZOLES 7/ 1988 110 BENZOTRIAZOLES 7/ 1988 111 SAR BENZOTRIAZOLES Organism: Daphnid Duration: 48 h Endpoint: LC50 (Mortality)

Equation: To determine the acute toxicity of benzotriazoles to daphnids use the neutral organic daphnid 48 h LC50 SAR.

Statistics:

Maximum log Kow : 5.0 Maximum MW: 1000.0 Application: The neutral organic SAR may be used to estimate the toxicity of substituted benzotriazoles with substitution on the 5th position, log Kow values of less than 5.0, and molecular weights less than 1000. Toxicity estimates for substituted benzotriazoles with substitutions on the triazole ring may not be valid with this SAR.

This SAR may be used for substituted benzotriazoles with substitutions on the 3rd, 4th or 6th positions (other benzo positions).

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: Nabholz JV. 1987. Generic review of various benzotriazoles. Washington, DC: Environmental Effects Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency.

LIST OF BENZOTRIAZOLES USED TO DEVELOP THE DAPHNID 48 h LC50 SAR. ____________________________________________________________________________________ ____ LC50 Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ Benzotriazole 141.6 1.45 N 5 Butylbenzotriazole 10.7 3.68 N ____________________________________________________________________________________ ____

N = Nabholz (1987). BENZOTRIAZOLES 7/ 1988 112 BENZOTRIAZOLES 7/ 1988 113 SAR BENZOTRIAZOLES Organism: Green Algae Duration: 96 h Endpoint: EC50 and EC10 (Growth)

Equation: Log EC50 (mM/ L) = 0.061  0.573 log Kow The 96 h EC10 may be determined by:

EC10 = EC50/ 8 Statistics: N = 2; R 2 = 1.00 Maximum log Kow : 8.0 Maximum MW: 1000.0 Application: This SAR may be used to estimate the toxicity of substituted benzotriazoles with substitution on the 5th position. Toxicity estimates for substituted benzotriazoles with substitutions on the triazole ring may not be valid with this SAR.

This SAR may be used for substituted benzotriazoles with substitutions on the 3rd, 4th or 6th positions (other benzo positions).

Limitations: If the log Kow value is greater than 8.0, or if the compound is solid and the EC50 or EC10 exceeds the water solubility, no effects expected at saturation.

References: Nabholz JV. 1987. Generic review of various benzotriazoles. Washington, DC: Environmental Effects Branch, Health and Environmental Review Division (TS 796), Office of Toxic Substances, United States Environmental Protection Agency.

LIST OF BENZOTRIAZOLES USED TO DEVELOP THE GREEN ALGAE 96 h EC50 AND EC10 SARs. ____________________________________________________________________________________ ____ EC50 EC10 Log Ref. CHEMICAL (mg/ L) (mg/ L) Kow ____________________________________________________________________________________ ____ Benzotriazole 15.4 1.75 1.45 N 5 Butylbenzotriazole 1.18 0.16 3.68 N ____________________________________________________________________________________ ____

N = Nabholz (1987) BENZOTRIAZOLES 7/ 1988 114 BENZOTRIAZOLES 7/ 1988 115 CARBAMATES 7/ 1988 116 SAR CARBAMATES Organism: Sea Urchin Duration: 48 h Endpoint: NEC (Early Development)

Equation: Log NEC (mM/ L) = 0.51  0.72 log Kow Statistics: N = 35; R 2 = 0.62 Maximum log Kow : 4.5 Maximum MW: 1000.0 Application: This SAR may be used to estimate toxicity for carbamates and the following classes of carbamates:

1. Alkyl esters of carbamic acid 2. N alkyl or aryl substitutes on ethyl carbamate 3. Bis( ethylcarbamates) joined at NRN by alkyl or aryl groups 4. Bis and tris carbamates esterified on a single phenyl ring 5. Thiocarbamates This SAR may be used for other similar substituted carbamates with log Kow values less than 4.5 and molecular weights less than 1000.

Limitations: The following classes of carbamates are more toxic than predicted by this SAR:

1. Meta phenylene bis( ethyl carbamates)  200 X 2. N methyl ortho phenyl biscarbamates  1000 X 3. N methyl para phenyl biscarbamates  400 X 4. N, N dimethyl 1,2,3 phenyl triscarbamates  400 X If the log Kow value is greater than 4.5, or if the compound is solid and the NEC exceeds the water solubility, no effects expected at saturation.

References: Cornman I. 1950. Inhibition of sea urchin egg cleavage by a series of substituted carbamates. Journal of the National Cancer Institute 50: 1123 1138. CARBAMATES 7/ 1988 117 LIST OF CARBAMATES USED TO DEVELOP THE SEA URCHIN 48 h NEC SAR. ____________________________________________________________________________________ ____ 48 h NEC Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ CARBAMATES USED FOR THIS SAR Methyl carbamate 2000.0 0.70 C Ethyl carbamate 999.0 0.18 C 1,2 Hydrazine di( ethylcarboxylate) 2000.0 0.11 C 1,2 Hydrazine di( ethylcarboxylate) 1000.0 0.11 C N methyl ethylcarbamate 10.3 0.37 C N, N dimethyl ethylcarbamate 994.0 0.42 C Propylene bis( ethylcarbamate) 998.0 0.58 C 1,4 Phenylene bis( N, N dimethyl carbamate 501.0 0.88 C 1,4 Phenylene bis( N, N dimethyl carbamate 101.0 0.88 C N ethyl ethylcarbamate 99.0 0.90 C Ethylidene bis( ethylcarbamate) 100.0 0.97 C Ethylene bis( ethylcarbamate) 100.0 0.98 C Tetramethylene bis( ethylcarbamate) 998.0 0.58 C N isopropyl ethylcarbamate 9.2 1.21 C 3 Methylbutyl carbamate 10.5 1.28 C Cyclohexyl carbamate 1.43 1.33 C N, N propyl ethylcarbamate 97.0 1.43 C N, N diethyl ethylcarbamate 95.7 1.48 C N, N cyclopentamethylene ethylcarbamate 39.1 1.61 C N, N diethyl ethylcarbamodithioate <41.0 1.68 C N, N butyl ethylcarbamate 8.7 1.96 C 1,3 Phenylene bis( N, N dimethyl carbamate <39.0 2.09 C N, N di isopropyl ethylcarbamate 92.0 2.09 C N ethyl ethylcarbamothioate <39.0 2.09 C Para xylylene bis( ethylcarbamate) 19.6 2.14 C Hexamethylene bis( ethylcarbamate) 502.0 2.16 C Hexamethylene bis( ethylcarbamate) 99.0 2.16 C N phenyl ethylcarbamate 1.0 2.29 C N cyclohexyl ethylcarbamate 1.7 2.40 C Ortho phenylene bis (ethylcarbamate) 20.2 2.44 C N, N di n propyl ethylcarbamate 9.4 2.53 C N, N di n butyl ethylcarbamate 10.0 3.59 C N, N diphenyl ethylcarbamate 9.6 NC C N decyl carbamate 1.0 4.06 C N n octyl ethylcarbamate 1.0 4.07 C N 2 fluorene ethylcarbamate <0.10 4.34 C 2,7 fluorene bis( ethylcarbamate) * 4.52 C CARBAMATES 7/ 1988 118 ____________________________________________________________________________________ ____

CONTINUED. ____________________________________________________________________________________ ____ 48 h NEC Log Ref. CHEMICAL (mg/ L) Kow ____________________________________________________________________________________ ____ CARBAMATES USED FOR THIS SAR n Dodecyl carbamate * 5.12 C N n decyl ethylcarbamate * 5.13 C CARBAMATES WITH EXCESSIVE TOXICITY 1,2 Phenylene bis( N methyl carbamate 0.9 0.11 C 1,3 Phenylene bis( N methyl carbamate 0.9 0.11 C 1,4 Phenylene bis( n methyl carbamate 0.9 0.45 C 1,2,3 Phenylene tris( N, N dimethyl carbamate 10.2 2.44 C ____________________________________________________________________________________ ____

* No effects in a saturated solution.