Page 2 of 103

TABLE OF CONTENTS 

EXECUTIVE SUMMARY .......................................................................................................... 8

1.0 INTRODUCTION ........................................................................................................... 12

2.0 ENVIRONMENTAL FATE ASSESSMENT ................................................................ 14

2.1 Product Chemistry and Chemical Structure ................................................................... 14

2.2 Summary of Abiotic Environmental Fate Processes ...................................................... 15

2.3 Summary of Biotic Environmental Fate Processes ........................................................ 15

2.4 Summary of Environmental Transport Processes .......................................................... 15

2.5 Summary of Environmental Fate in Wastewater Treatment .......................................... 16

2.0 HUMAN HEALTH RISK ASSESSMENT .................................................................... 17

3.1 Hazard Assessment ....................................................................................................... 17

3.2.1 FQPA Considerations ................................................................................................. 19

3.3 Dietary Assessment ........................................................................................................ 20

3.2.2 Dietary Exposure and Risk Analysis ...................................................................... 20

3.3 Residential Non-Dietary Assessment ............................................................................. 25

3.4 Aggregate and Cumulative Exposure ............................................................................. 26

3.4.1 Aggregate Exposures .............................................................................................. 26

3.4.2 Cumulative Exposures ............................................................................................ 26

3.5 Occupational Exposure .................................................................................................. 26

3.7 Human Health Risk Characterization ............................................................................. 27

3.0 ECOLOGICAL RISK ASSESSMENT .......................................................................... 28

4.1 Selected Ecological Toxicity Endpoints ........................................................................ 28

4.1.1 Effects to Wastewater Treatment Plant Microorganisms ....................................... 29

4.2 Summary of Ecological Exposure Assessment Approach ............................................. 30

4.2.1 EPA’s Estimation of Exposure of Freshwater Fish and Invertebrates to ATMD in 

the Water Column ................................................................................................................. 31

4.2.2 EPA’s Estimation of Exposure of Freshwater Benthic Invertebrates to ATMD in 

Sediments .............................................................................................................................. 32
Page 3 of 103

4.2.3 EPA’s Estimation of Exposure of Estuarine/Marine Fish and Invertebrates to 

ATMD in the Water Column ................................................................................................ 33

4.2.4 EPA’s Estimation of Exposure of Estuarine/Marine Benthic Invertebrates to 

ATMD in Sediments ............................................................................................................. 34

4.2.5 EPA’s Estimation of Exposures to Piscivorous Birds and Mammals ..................... 34

4.2.6 Mexel’s Estimation of Exposure to ATMD Released from Cooling Towers and 

Once-Through Industrial Cooling Water Systems ................................................................ 34

4.3 Estimation of Risks to Aquatic Organisms .................................................................... 35

4.3.1 Estimation of Risks to Freshwater Organisms Exposed to ATMD in the Water 

Column 35

4.3.2 Estimation of Risks to Freshwater Benthic Invertebrates Exposed to ATMD in 

Sediments .............................................................................................................................. 42

4.3.3 Estimation of Risks to Estuarine/Marine Organisms Exposed to ATMD in the 

Water Column ....................................................................................................................... 43

4.3.4 Estimation of Risks to Estuarine/Marine Benthic Invertebrates Exposed to ATMD 

in Sediments .......................................................................................................................... 44

4.3.5 Estimation of Risks to Piscivorous Birds and Mammals ........................................ 45

4.4 Ecological Risk Characterization ................................................................................... 45

Evaluation of EPA’s Ecological Exposure and Risk Assessment Modeling Results ........... 45

Uncertainties Resulting from Gaps in Ecotoxicity Data ....................................................... 47

Uncertainties Resulting from Gaps in Environmental Fate Data .......................................... 47

Evaluation of Modeling Results Provided by Mexel ............................................................ 48

Evaluation of WET Results Submitted by Mexel ................................................................. 50

4.7 Section 4 References ...................................................................................................... 51

5.0 SUMMARY OF POTENTIAL HUMAN AND ECOLOGICAL RISKS ................... 52

APPENDIX A: ENVIRONMENTAL FATE DATA ............................................................ 57

Introduction ............................................................................................................................... 57

Product Chemistry .................................................................................................................... 59

Environmental Fate ................................................................................................................... 60

Hydrolysis ............................................................................................................................. 60

Photodegradation in Water ................................................................................................... 60

Aerobic Aquatic Metabolism ................................................................................................ 61

Anaerobic Aquatic Metabolism ............................................................................................ 61
Page 4 of 103

Leaching-Adsorption-Desorption ......................................................................................... 61

Bioconcentration in Fish ....................................................................................................... 62

Sorption to Activated Sludge ................................................................................................ 62

Activated Sludge Respiration Inhibition (ASRI) .................................................................. 63

Biodegradability in Wastewater Treatment .......................................................................... 63

APPENDIX B: HUMAN HEALTH TOXICITY DATA ...................................................... 69

APPENDIX C: ECOTOXICITY DATA ................................................................................ 80

Toxicity to Terrestrial Organisms ............................................................................................. 80

Birds ...................................................................................................................................... 80

Nontarget Insects .................................................................................................................. 82

Toxicity to Aquatic Organisms ................................................................................................. 82

Freshwater Fish ..................................................................................................................... 82

Whole Effluent Toxicity Testing .............................................................................................. 90

Calvert Cliffs Nuclear Power Plant (CCNPP) Whole Effluent Toxicity Testing ................. 90

Donald C. Cook Nuclear Power Plant (DCCNPP) Whole Effluent Toxicity Testing .......... 92

Whole Effluent Toxicity Study References .............................................................................. 93

APPENDIX D: RISK ESTIMATION METHODS ............................................................... 95

APPENDIX E: ECOLOGICAL EXPOSURE MODELING METHODOLOGY ............. 97

Methodology for Estimating Water Column Exposure to Aquatic Organisms from Release of 

ATMD from Recirculating Cooling Towers............................................................................ 97

Methodology for Estimating Exposure to Aquatic Organisms from Release of ATMD from 

Once-through cooling systems ................................................................................................ 101

Description of High-End Versus Average Case Scenario ...................................................... 102

Methodology for Estimating Sediment Exposure to Benthic Aquatic Organisms from Release 

of ATMD from Once-Through and Recirculating Cooling Towers ....................................... 102

APPENDIX E – REFERENCES ............................................................................................ 103

 
Page 5 of 103

LIST OF TABLES 

Table 1: Endpoints for use in ATMD Drinking Water Assessments ........................................... 19

Table 2: Estimated Drinking Water Concentrations (EDWCs) of ATMD for Surface Water 

using the E-FAST Model .............................................................................................................. 22

Table 3: Summary of Acute and Chronic Dietary Exposure and Risk Analyses for ATMD (Endof-pipe water concentration) ......................................................................................................... 22

Table 4: Summary of Acute and Chronic Dietary Exposure and Risk Analyses for ATMD (Once 

through cooling system, 0% removal, 10th percentile ratio of stream flow to plant flow) .......... 23

Table 5: Summary of Acute and Chronic Dietary Exposure and Risk Analyses for ATMD (Once 

through cooling system, 0% removal, 50th percentile ratio of stream flow to plant flow) .......... 24

Table 6: Summary of Acute and Chronic Dietary Exposure and Risk Analyses for ATMD 

(Recirculating cooling tower, 0% removal, 10th percentile ratio of stream flow to plant flow) .. 24

Table 7: Effects Endpoints Selected for Assessing Ecological Risks to ATMD ......................... 28

Table 8: Estimated Concentrations of ATMD in Freshwater Benthic Sediment Based on 10th 

and 50th Percentile Surface Water Concentrations Estimated from the General Population 

Exposures and Industrial Releases Module of E-FAST ............................................................... 33

Table 9: Estimates of Numbers of Day Per Year of Exceedance of Acute COCs for Freshwater 

Organisms Downstream of Moderate-Size Recirculating Cooling Towers (0.0029 kg/site/day 

release of ATMD before treatment based on 2.5 ppm residual of product (42.5 ug/L active 

ingredient)) .................................................................................................................................... 36

Table 10: Estimates of Numbers of Day Per Year of Exceedance of Endangered/Listed COCs 

for Freshwater Organisms Downstream of Moderate-Size Recirculating Cooling Towers (0.0029 

kg/site/day release of ATMD before treatment based on 2.5 ppm residual of product (42.5 ug/L 

active ingredient)) ......................................................................................................................... 37

Table 11: Estimates of Numbers of Day Per Year of Exceedance of Chronic COCs for 

Freshwater Organisms Downstream of Moderate-Size Recirculating Cooling Towers (0.0029 

kg/site/day release of ATMD before treatment based on 2.5 ppm residual of product (42.5 ug/L 

active ingredient)) ......................................................................................................................... 37

Table 12: Estimates of Numbers of Day Per Year of Exceedance of Acute COCs for Freshwater 

Organisms Downstream of Large-Size Recirculating Cooling Towers (0.0029 kg/site/day release 

of ATMD before treatment based on 2.5 ppm residual of product (42.5 ug/L active ingredient))

....................................................................................................................................................... 38

Table 13: Estimates of Numbers of Day Per Year of Exceedance of Endangered/Listed COCs 

for Freshwater Organisms Downstream of Large-Size Recirculating Cooling Towers (0.0029 

kg/site/day release of ATMD before treatment based on 2.5 ppm residual of product (42.5 ug/L 

active ingredient)) ......................................................................................................................... 38

Table 14: Estimates of Numbers of Day Per Year of Exceedance of Chronic COCs for 

Freshwater Organisms Downstream of Large-Size Recirculating Cooling Towers (0.0029 
Page 6 of 103

kg/site/day release of ATMD before treatment based on 2.5 ppm residual of product (42.5 ug/L 

active ingredient)) ......................................................................................................................... 39

Table 15: Estimates of Numbers of Days of Exceedance of COCs for Freshwater Organisms 

Downstream of Once-through cooling systems with an Intake Flow of 2 Million Gallons per Day 

(MGD) Assuming No Treatment and 2.5 ppm Residual of Product (42.5 ug/L active ingredient, 

ATMD) ......................................................................................................................................... 39

Table 16: Estimates of Numbers of Days of Exceedance of COCs for Freshwater Organisms 

Downstream of Once-through cooling systems with an Intake Flow of 20 Million Gallons per 

Day (MGD) Assuming No Treatment and 2.5 ppm Residual of Product (42.5 ug/L active 

ingredient, ATMD) ....................................................................................................................... 40

Table 17: Estimates of Numbers of Days of Exceedance of COCs for Freshwater Organisms 

Downstream of Once-through cooling systems with an Intake Flow of 50 Million Gallons per 

Day (MGD) Assuming No Treatment and 2.5 ppm Residual of Product (42.5 ug/L active 

ingredient, ATMD) ....................................................................................................................... 41

Table 18: Estimates of Numbers of Days of Exceedance of COCs for Freshwater Organisms 

Downstream of Once-through cooling systems with an Intake Flow of 100 Million Gallons per 

Day (MGD) Assuming No Treatment and 2.5 ppm Residual of Product (42.5 ug/L active 

ingredient, ATMD) ....................................................................................................................... 41

Table 19: Risk Quotients for Freshwater Benthic Organisms Based on Estimated Concentrations 

of ATMD in Sediment (sediment concentrations for 10th and 50th percentile 7Q10 Distribution)

....................................................................................................................................................... 42

Table 20: Concentrations of Concern for Risk to Water Column-Dwelling Estuarine/Marine 

Organisms and Dilution Factors That Would Minimize Risks ..................................................... 44

Table 21. Chemical, Physical, and Environmental Fate Properties of Duomeen C from EPI-Suite 

4.11 and Guideline Studies ........................................................................................................... 64

Table 22: Avian Acute-Oral Toxicity .......................................................................................... 81

Table 23: Avian Dietary Toxicity ................................................................................................ 81

Table 24: Freshwater Fish Acute Toxicity ................................................................................... 82

Table 25: Freshwater Fish Chronic Toxicity ............................................................................... 83

Table 26: Freshwater Invertebrates Acute and Chronic Toxicity ................................................ 83

Table 27: Estuarine/Marine Invertebrates Acute and Chronic Toxicity ...................................... 84

Table 28: Aquatic Plant Toxicity ................................................................................................. 85

Table 29: Subchronic Sediment Toxicity .................................................................................... 86

Table 30: Summary of Whole Effluent Toxicity Test Results for CCNPP in 2011 during Mexel 

Treatment Trial ............................................................................................................................. 91

Table 31: Summary of Whole Effluent Toxicity Test Results for DCCNPP in 2006 and 2007 

during Mexel Treatment Trial ....................................................................................................... 93

Table 32 Risk Presumption Categories ........................................................................................ 95

 
Page 7 of 103

LIST OF FIGURES 

Figure 1: Chemical Structure of Dodecyl-1,3-propanediamine. .................................................. 14

   
Page 8 of 103

EXECUTIVE SUMMARY

 This document presents the United States Environmental Protection Agency’s human and 

ecological risk assessment for the new use of the active ingredient, N-coco 1,3-diaminopropane 

(also sometimes referred to as N-(coco alkyl)trimethylenendiamine, Duomeen C, and ATMD) in 

MEXEL 432/0 to control biofouling in once-through and recirculating cooling towers. The 

active ingredient in MEXEL 432/0 is generally hereinafter referred to as ATMD 

(alkyltrimethylenediamine). 

 MEXEL 432/0 is to be used for the control of biofouling, including zebra mussels and 

clams in once-through cooling and cooling tower circuits with closed delivery systems for nonpotable industrial freshwater and sea water systems. The product may be applied to maintain 

clean systems or to treat systems that are already fouled. Normal frequency of treatment is once 

per day or as needed to maintain control. The amount of the daily dose is determined by the 

circuit characteristics. The daily dose is 4.0 ppm for 30 minutes with a residual concentration of 

2.5 ppm. 

 According to the product label, the concentration of active ingredient, ATMD, is 1.7 

percent. Based on maintenance of 2.5 ppm product residual, this corresponds to 42.5 ug/L 

ATMD. 

 ATMD would not be expected to pose higher risks to aquatic organisms than alternative 

chemical substances that could be used as biofoulants in recirculating cooling tower and oncethrough cooling systems. Since facilities that would be expected to use this product already have 

NPDES permits for biofoulants, there would be no increased risks to aquatic systems nor 

increased regulatory burden for permit writers from the use of ATMD. 

 The exposure scenarios that form the basis of EPA’s risk assessment include releases to 

surface water from large-and moderate size recirculating cooling towers and, once-through 

cooling systems. For recirculating cooling towers, exposures from releases of ATMD to surface 

water were estimated with and without wastewater treatment. For once-through cooling systems, 

it was assumed that no treatment of effluent occurs prior to discharge to surface water. 

 This risk assessment considers risks to both humans and ecological organisms. Risks to 

humans evaluated in this assessment include potential dietary risks from ingestion of drinking 

water and potential risks from occupational exposure during mixing and loading of ATMD. 

Estimates of potential dietary risks to humans from ingestion of drinking water were determined 

to be negligible based on worst case estimates of drinking water concentrations and published 

information on drinking water consumption by humans at a high level of consumption. 

 Although potential risks were identified for occupational dermal and inhalation exposure 

during mixing and loading, these risks can be minimized if the proposed product label is 
Page 9 of 103

modified to specify “closed loading and delivery systems”. (The proposed label only specifies 

“closed delivery systems”.) 

 The ecological risk assessment and characterization for ATMD considers three key 

components: 

 EPA’s assessment of risks to ecological organisms from exposure to ATMD; 

 Whole Effluent Toxicity (WET) test data submitted by the registrant from two once 

through cooling systems; and 

 Site-Specific modeling submitted by the registrant. 

EPA ecological modeling results are based on loadings that would estimate surface water 

concentrations for peak exposures. According to use instructions on the proposed label, the daily 

dose of MEXEL 432/0 is 4.0 ppm for 30 minutes with a residual concentration of 2.5 ppm. (The 

residual concentration of ATMD at 1.7% in product would be 42.5 ug/L.) The proposed label 

also states that normal frequency of treatment is once per day or as needed to maintain control. 

Since the proposed label contained no upper limit on the frequency of treatment on a daily basis, 

EPA assumed that a 2.5 ppm residual product (42.5 ug/L ATMD) would be maintained 

continuously over a 24-hour period. This assumption serves two purposes: (1) It provides 

estimates of peak exposures that are needed to estimates acute risks to aquatic organisms and (2) 

it provides a worst case exposure estimate based on the lack of an upper limit of application 

frequency on the product label. 

 If the maximum application of MEXEL 432/0 is limited to a single dose applied daily for 

30 minutes, peak daily hourly and chronic peak risk estimates used to assess exposures to aquatic 

organisms would be reduced. Based on guidelines for Whole Effluent Toxicity tests, for acute 

criteria, EPA recommends an averaging period of 1 hour and for chronic criteria an averaging 

period of 4 days. Based on these guidelines, daily loadings that EPA used in its modeling for 

calculating acute exposures would decrease by a factor of 2 and for chronic exposures by a factor 

of 48. These adjustments would reduce EPA’s estimates of acute and chronic exposures and 

risks to aquatic organisms in the water column. 

 When interpreting the results of EPA’s human and ecological risk assessment, it is 

important to note that sorption of ATMD to suspended solids in the water column was not 

quantitatively considered since EPA’s E-FAST model was unable to account for this 

phenomenon. By extrapolation from laboratory studies on adsorption/desorption of ATMD in 

soils, ATMD would be expected to have a very high potential to sorb to suspended sediments in 

the water column. Accounting for sorption of ATMD to suspended sediments in the water 

column would further reduce EPA’s estimates of acute and chronic exposures and risks to 

aquatic organisms in the water column. 
Page 10 of 103

 Two general quantitative approaches were used by EPA to assess risks to ecological 

organisms: a risk quotient (RQ) method and a probabilistic method (These are discussed further 

in Appendix D). 

 The probabilistic approach was used to estimate potential risks to freshwater fish and 

invertebrates. Risk estimates are provided as number of days per year of exceedance of 

concentration of concern (COC) downstream of a facility. Exceedance of an acute COC and of 

an endangered/listed acute COC for one day per year or more indicates that there may be 

potential for acute adverse effects to freshwater organisms. Exceedance of chronic COCs for 20 

days or more indicates that there may be potential chronic adverse effects to freshwater 

organisms. Both average case and high end scenarios were evaluated. For the high-end 

scenario, results of the number of days per year that COCs are exceeded is based on the upper 

10th percentile of the ratio of stream flows to plant flows (Also referred to as Stream Dilution 

Factors (SDFs) . For the average case scenario, results of the number of days per year that COCs 

are exceeded are based on the 50th percentile of SDFs. For the upper 10th percentile SDFs, or 

high-end scenario, the stream flow to plant flow ratio is relatively low since plant flows can 

contribute considerable volume to the flow of the stream and resulting surface water 

concentrations can be relatively high. For the 50th%ile SDF, the stream flow to plant flow ratio 

is more typical. The risk quotient method was used to estimate potential risks to freshwater 

benthic invertebrates, marine/estuarine freshwater fish and invertebrates, and estuarine/marine 

benthic organisms. 

 For recirculating cooling towers on freshwater streams:. Based on the average case 

scenario, there are few risks of concern for the moderate-size system even when no treatment of 

released water is considered. For large systems, concentrations of concern for algae are 

potentially exceeded for up to 17 days per year and exceedances are 1-6 days for other 

organisms. When treatment is considered, days when COC are exceeded are up to 7 days for 

algae and 0-2 days for other aquatic organisms. For estuarine systems, RQ’s (assuming end-ofpipe concentrations) are 0.3 for fish, 2.2 for invertebrates and 3.9 for algae. 

 For once-through cooling systems on freshwater streams: Based on the average case 

scenario for small systems (2 million gallons per day), concentrations of concern for algae are 

potentially exceeded for up to 26 days per year, exceedances are 3-10 days for other organisms. 

For large systems (100 million gallons per day), concentrations of concern for algae are 

potentially exceeded for up to 160 days per year, exceedances are 39-83 days for other 

organisms. Acute RQs for estuarine organisms range up to 4.8 and chronic RQs range up to 8.3. 

There is generally no treatment of water for once-through cooling systems; therefore, no 

treatment was assumed for this assessment. 

 A qualitative approach was used to conclude that the potential risks to piscivorus birds 

and mammals from the use of ATMD in cooling systems are low. 
Page 11 of 103

 Releases of ATMD from recirculating cooling towers to receiving water bodies and 

associated exposures are predicted to be much lower than those from once-through cooling 

systems. First, releases from recirculating cooling towers are from blowdown water, which 

constitutes a fraction of the total cooling tower intake flow, whereas releases from once-through 

cooling systems consist of the total intake flow. (Blowdown is assumed to be only 0.06 percent 

of recirculating cooling tower intake flow.) Second, effluents from recirculating cooling towers 

may possibly undergo wastewater treatment whereas effluents from once-through cooling 

systems would not. 

 In a non-guideline study submitted to the Agency (Ackerman, D, F Ghillebaert, and 

M.W. Glass, 2013: MRID 49040220), Mexel used two modeling approaches to estimate 

exposures and risks to aquatic organisms downstream of two power plants which Mexel 

considered to be atypical and to have the greatest impact. Results on days per year of 

exceedance for the two facilities modeled are general (presented in graphs) with no results 

provided for specific COCs. Although the two facilities modeled by Mexel might provide 

conservative estimates of exposure relative to other facilities where ATMD could be used, EPA 

cannot conclude based on modeling results that the use of ATMD at these types of facilities will 

not pose potential concerns for exposure and risk to aquatic organisms. . 

 Whole effluent toxicity testing from two facilities, Calvert Cliffs Nuclear Power Plant 

(CCNPP) and Donald C. Cook Nuclear Power Plant (DCCNPP) conducting efficacy trials with 

Mexel were submitted by the registrant (MRID 49208816); details of these studies are provided 

in Appendix E. Both facilities have once through cooling systems. The studies show that under 

certain dosing regimes and mixing zones there are facilities that would be able to use Mexel in 

once through cooling systems without resulting in unreasonable adverse effects to the aquatic 

environment. For facilities that need to meet limits at the end-of-pipe, however, the proposed 

label rate would result in exceedances for once-through systems. 

 Major uncertainties with the risk assessment are associated with gaps in ecotoxicity and 

environmental fate data. The Agency used models and acute to chronic ratio calculations to 

account for missing data. Additionally, no ecotoxicity data are available for the formulated 

product. Data for the TGAI, which comprises 1.7% of the product, may underestimate the 

toxicity of the formulation. The Agency assumed stability of ATMD in the aquatic environment 

since no aquatic metabolism studies provided information on degradates. Further, when 

interpreting the results of EPA’s human and ecological risk assessment, it is important to note 

that sorption of ATMD to suspended solids in the water column was not quantitatively 

considered; this would lead to overestimates of surface water concentrations predicted 

downstream of facilities where ATMD would be expected to be used. 

 
Page 12 of 103

1.0 INTRODUCTION

 This document presents the United States Environmental Protection Agency’s human and 

ecological risk assessment for the new use of the active ingredient, N-coco 1,3-diaminopropane 

(also sometimes referred to as N-(coco alkyl)trimethylenendiamine, Duomeen C, and ATMD) in 

MEXEL 432/0 to control biofouling in once-through and recirculating cooling towers. The 

active ingredient in MEXEL 432/0 is generally hereinafter referred to as ATMD 

(alkyltrimethylenediamine). 

 MEXEL 432/0 is to be used for the control of biofouling, including zebra mussels and 

clams in once-through cooling and cooling tower circuits with closed delivery systems for nonpotable industrial freshwater and sea water systems. The product may be applied to maintain 

clean systems or to treat systems that are already fouled. Normal frequency of treatment is once 

per day or as needed to maintain control. The amount of the daily dose is determined by the 

circuit characteristics. The daily dose is 4.0 ppm for 30 minutes with a residual concentration of 

2.5 ppm. 

 The concentration of active ingredient, ATMD, in MEXEL 432/0 is 1.7 percent. Based 

on maintenance of 2.5 parts per million (ppm) product residual, this corresponds to 42.5 

micrograms per liter (ug/L) ATMD. 

 The exposure scenarios that form the basis of EPA’s risk assessment include releases to 

surface water from: 

 large-size recirculating cooling towers; 

 moderate-size recirculating cooling towers; and 

 once-through cooling systems. 

For recirculating cooling towers, exposures from releases of ATMD to surface water were 

estimated with and without wastewater treatment. The estimates of percent removal during 

wastewater treatment are based on experimental results reported in the activated sludge sorption 

isotherm study submitted by the registrant and are based on sorption of the active ingredient by 

activated sludge after 4 and 6 hours under conditions that simulate an activated sludge basin 

(MRID 49040205; Schaefer, E and A Ponizovsky (2012). Four hours of treatment is considered 

the low end of the duration of treatment in an activated sludge aeration basin and six hours of 

treatment is considered to be the average period of treatment. 

 For once-through cooling systems, it was assumed that no treatment of effluent occurs 

prior to discharge to surface water. 

 This risk assessment considers risks to both humans and ecological organisms. Risks to 

humans evaluated in this assessment include potential dietary risks from ingestion of drinking 
Page 13 of 103

water and potential risks from occupational exposure during mixing and loading of ATMD. 

Worst case estimates of drinking water concentrations were derived from end of pipe 

concentrations of ATMD and high-end estimates of surface water concentrations from EPA’s 

Exposure and Fate Assessment Screening Tool (E-FAST) model. By extrapolation from 

laboratory studies on adsorption/desorption of ATMD in soils, ATMD would be expected to 

have a very high potential to sorb to suspended sediments in the water column. Since EPA’s 

models were unable to account for the phenomenon of sorption of ATMD to suspended 

sediments in the water bodies downstream of facilities where ATMD can be used, estimated 

surface water concentrations do not quantitatively consider this phenomenon. 

 The ecological risk assessment considers three key components: 

 EPA’s assessment of risks to ecological organisms from exposure to ATMD; 

 Site-Specific modeling submitted by the registrant, and. 

 Whole Effluent Toxicity (WET) test data submitted by the registrant; and 

 In EPA’s assessment of risks to ecological organisms from exposure to ATMD, two 

general quantitative approaches were used to assess risks: a risk quotient (RQ) method and a 

probabilistic method (These are discussed further in Appendix D). The probabilistic approach 

was used to estimate potential risks to freshwater aquatic organisms. The risk quotient method 

was used to estimate potential risks to both freshwater and estuarine/marine benthic 

invertebrates, and to estuarine/marine organisms in the water column. In addition, for 

marine/estuarine fish and invertebrates, dilution factors that would be needed to mitigate 

exceedance of concentrations of concern were estimated. In estimating sediment concentrations 

of ATMD to which freshwater benthic organisms would be exposed, estimated surface water 

concentrations were multiplied by average experimentally-determined leaching 

adsorption/desorption values. In estimating sediment concentrations to which estuarine/marine 

organisms would be exposed, the effluent concentration of ATMD at the end of pipe determined 

from information on the product label was multiplied by average experimentally-determined 

leaching adsorption/desorption values. A qualitative approach was used to estimate potential 

risks to piscivorus birds. 

 EPA evaluated modeling information submitted by the registrant. In a non-guideline 

study submitted to the Agency (Ackerman, D, F Ghillebaert, and MW Glass, 2013: MRID 

49040220), Mexel used two modeling approaches to estimate exposures and risks to aquatic 

organisms downstream of two power plants. The first modeling approach used the site-specific 

option of the General Population and Ecological Exposure from Industrial Releases module of EFAST to provide screening level estimates of exposures to aquatic organisms and the second 

approach used the higher tier CE-QUAL-W2 model to provide more refined estimates of 

exposures to aquatic organisms. Mexel considered the two power plants they selected for 

modeling to be atypical and to have the greatest impact. 
Page 14 of 103

 EPA evaluated whole effluent toxicity testing submitted by the registrant from two 

facilities, Calvert Cliffs Nuclear Power Plant (CCNPP) and Donald C. Cook Nuclear Power 

Plant (DCCNPP) conducting efficacy trials with MEXEL 432/0 were submitted by the registrant 

(MRID 49208816) and evaluated by the Agency; details of these studies are provided in 

Appendix C. CCNPP is located along an estuarine area of the Potomac River and DCCNPP is 

located along the shore of Lake Michigan. Both facilities have once through cooling systems. 

The design flow is 3460 million gallons per day at CCNPP and 2405 million gallons per day at 

CCNPP. 

2.0 ENVIRONMENTAL FATE ASSESSMENT

2.1 Product Chemistry and Chemical Structure

 ATMD is an alkyl triethylene diamine surfactant (surface acting agent) with an alkyl 

chain that contains 8-18 carbons in even increments. The predominant alkyl chain constituents 

(C12, C14, C16, and C18) account for 45.3, 16.2, 9.5, and 11.1 percent of the total mixture, 

respectively. Taken together, the four predominant constituents account for 82.1 % of the parent 

mixture. The remaining diamine compounds (C8 and C10) account for a total of 9.3 % of the 

parent mixture (MRID 49040203). Figure 1 below contains the structure of the primary 

compound (C12), which accounts for 45 % of the total diamine mixture. 

Figure 1: Chemical Structure of Dodecyl-1,3-propanediamine. 

 The registrant submitted product chemistry studies for their product which contain 

information that appears to be useful for risk assessment. The ultraviolet (UV) visible absorption 

spectrum study indicates that the maximum sorption is in the range of 202-218 nanometers (nm) 

of wavelength, with only a small amount of absorption in the 290-350 nm range (MRID 

49040202). As a result of this limited UV sorption, minimal photodegradation by sunlight is 

expected. The weighted average1

 octanol-water partitioning coefficient (log P) of the N-coco-

 

1

 Weighted arithmetic mean of (log P for each compound * percentage in mixture)/91.4 % diamine content. 

H 3 C

N H

N H 2
Page 15 of 103

1,3-diaminopropane product was 0.2 (unitless), but it ranged from -3 (for C8 alkyl chain) to 2-2.5 

(for C18 alkyl chain) [MRID 49040203]. Based on this log P value, this mixed product can 

bioconcentrate but is not expected to have high bioconcentration in aquatic organisms.2,

3

 The 

water solubility for the entire product is relatively low because of the alkyl carbon chain, and is 

approximately 10 milligrams per liter (mg/l or ppm) (MRIDs 49040204, 48486702).

2.2 Summary of Abiotic Environmental Fate Processes

 ATMD is stable to hydrolysis at pH 5, 7, and 9 (MRIDs 40062413, 41069001, and 

93034010) and is expected to undergo minimal photodegradation in water based on minimal 

sorption of UV light between 290-800 nm in wavelength (MRID 49040202). 

2.3 Summary of Biotic Environmental Fate Processes

 The registrant has not submitted guideline aquatic metabolism studies for ATMD. 

Aerobic aquatic metabolism (835.4300) represents the water column in a water body while 

anaerobic aquatic metabolism (835.4400) represents the bottom and suspended sediment. In lieu 

of aquatic metabolism guideline studies, the registrant provided literature studies to address the 

persistence of alkyl amines and degradates in sediment and water. Information in the literature 

studies4 demonstrated that degradation of alkylamines occurred by deamination followed by 

beta-oxidation of the alkyl chains, with successive formation of alkanal groups (alkane chain 

with aldehyde functional group) and fatty acids (carboxylic acids), which degrade to CO2, water, 

and bacterial biomass. However, none of these studies provided estimates of half-life of 

alkylamines or their metabolic intermediates, and therefore their persistence cannot be estimated 

at this time (MRIDs 49208802, 49208803). 

2.4 Summary of Environmental Transport Processes

 Based on soil sorption studies, ATMD was observed to tightly sorb with whole soil 

Freundlich adsorption values (Kf) of 14,454-50,898 L/kg and adsorption values normalized for 

soil organic carbon (Koc) of 696,677 - 4,551,033 L/Kg. In each of the five soils tested, nearly all 

(>99 %) of ATMD was sorbed within a 24-hour period. Sorption was related to cation exchange 

 

2

 TG OECD 305 states that a compound having a log P of >3 does not have “high” lipophilicity 3

 http://www.epa.gov/scipoly/sap/meetings/2008/october/305_bioconcentration_flowthrough_fish_test.pdf 4

 Cerniglia and Perry (1975), Nguyen et al. (2008), and van Ginkel et al. (2008) 
Page 16 of 103

capacity (CEC)5

 with a coefficient of determination (r2) of 0.55 which indicates that sorption is a 

function of clay content (r2=0.16), organic carbon content (r2=0.21), and pH (r2=0.33) (MRID 

49040206). 

 ATMD bioconcentrated in bluegill sunfish (Lepomis macrochirus) with steady state 

bioconcentration factors of 82-180X, 525-610X, and 378-388X for edible, non-edible, and whole 

fish, respectively. The 50 % depuration times were 17, 8.5-21, and 9.2-30 days for edible, nonedible, and whole fish, respectively (MRID 49040210). 

2.5 Summary of Environmental Fate in Wastewater Treatment

 In a wastewater treatment plant, the primary route of dissipation of ATMD is expected to 

be sorption to activated sludge. ATMD was strongly sorbed to activated sludge with Kf values 

of 39,753 and Koc values of 105,222 L/kg. The extent of sorption increased with time based on 

71-92 % sorption by 4-6 hours (mean of 83 %) and 94-98 % sorption by 12-24 hours (mean of 

96 %) (MRID 49040205). 

 ATMD is not expected to degrade rapidly in water or during wastewater treatment 

because it was not determined to be readily biodegradable in an OECD 301D Closed Bottle test 

(MRID 49040207). At 2 mg/l of ATMD, the registrant reported that 69 % of the theoretical 

oxygen demand (ThOD) was reached by 28 days, and therefore ATMD should be considered to 

be readily biodegradable. However, this result does not meet the pass criterion established for 

this guideline. The OECD 301D test guideline criterion for ready biodegradability in a Closed 

Bottle test is 60 % of ThOD in a 14-day period, and this 14-day period starts when 10 % of 

ThOD disappears and must end before day 28 of the test.6 In the study, 10 % ThOD 

disappearance occurred at approximately 8 days, and the maximum percent ThOD disappearance 

in any 14-day window was 42 % (from 8-22 days). 

The IC50 value for the ASRI test (MRID 49040218) was 22 mg/l with 95 % confidence bounds 

of 10-30 mg/l. 

 

5

 Cation exchange capacity (CEC) is the sum of the negative charges in the soil, which is affected by pH, organic 

carbon, and clay content. 

6

 P. 3, OECD 301, http://www.oecd.org/chemicalsafety/risk-assessment/1948209.pdf 
Page 17 of 103

2.0 HUMAN HEALTH RISK ASSESSMENT

3.1   Hazard Assessment

 For ATMD, the registrant submitted information to address the human health data 

requirements needed to assess the proposed use. Information is needed on subchronic toxicity, 

developmental toxicity, reproductive toxicity, chronic toxicity, carcinogenicity, and 

mutagenicity. The information submitted by the registrant consisted of one submitted 90-day 

oral toxicity study (MRID 49092801) reviewed by the Office of Pesticide Programs’ (OPP) 

Antimicrobials Division, and summaries of toxicity studies on subchronic (MRID 49208808), 

developmental (MRID 49208809), reproductive (MRID 49208810), chronic toxicity (MRID 

49208811), carcinogenicity (MRID 49208812), and neurotoxicity (MRID 49208813) cited in a 

2008 European risk assessment document (European Commission, 2008; information submitted 

under MRID 49208808). The studies cited in the 2008 European Commission risk assessment 

were conducted on certain ATMD structural analogs. Toxicity information also consists of a 

repeated dose toxicity study with developmental and reproductive screening (MRID 47646101) 

submitted on coco alkylamines (pc code 900960). The issue of structure-activity is discussed 

more below. Many of the cited studies (with the exception of the 90-day and 

developmental/reproductive screening study mentioned above) are from the open scientific 

literature and were submitted as summaries only. Summaries of all toxicity studies mentioned 

above are presented in Appendix B of this risk assessment. 

 The registrant proposed that ATMD structural analogs (such as those considered in the 

2008 European Union risk assessment) should be included as part of the hazard database for 

assessment of the proposed use of ATMD. The issue of structure-activity was discussed within 

the agency. The agency has determined that the data on the ATMD analogs summarized in the 

2008 European Commission risk assessment could be considered together with the data on 

ATMD, as the effects observed from toxicology studies conducted with these chemicals appear 

to be similar, and are related to the irritant properties of these chemicals. One difference appears 

to be the doses at which the effects are observed, with the diamine chemicals being more potent 

than the monoamine chemicals in causing irritant-like effects. 

3.2 Dose-Response Assessment

 The information submitted for assessment of human health hazard on ATMD consisted 

largely of summaries of toxicity studies conducted in experimental animals. As mentioned, many 

of these studies were cited from a 2008 European Union Risk Assessment on certain ATMD 

chemicals. 
Page 18 of 103

 OPP has developed and published a guidance document 

(http://www.epa.gov/pesticides/science/lit-studies.pdf) regarding the adequacy of scientific 

literature studies submitted in support of a human health risk assessment. To be considered 

adequate, information from the open literature should be presented as the full article and not a 

summary. All of the cited studies from the 2008 European Commission risk assessment were 

submitted as summaries only. This hinders a full hazard evaluation and dose-response 

assessment of the mammalian toxicity data for the proposed use of ATMD. 

 Table 1 presents endpoints used in the ATMD drinking water assessment. Lacking full 

study reports for review, the No Observable Adverse Effect (NOAEL) value of 0.4 milligrams 

per kilogram per day (mg/kg/day) from the 90-day oral toxicity study (MRID 49092801) is used 

as a conservative endpoint for the assessment of acute and chronic risk from drinking water 

exposure to ATMD for the proposed use. This endpoint is conservative because it currently is 

the lowest NOAEL value from the database on ATMD chemicals. The acute and chronic 

assessments are conducted using the same endpoint (0.4 mg/kg/day) and uncertainty factor (100). 

An extra uncertainty factor for extrapolation to assess chronic risk is not needed, based on the 

main effects of the chemical being portal-of-entry type effects (e.g. irritation) and that under 

relevant exposure conditions, these effects would not be expected to occur at lower doses with 

increased duration of exposure. 

 This approach is also consistent with the approach to assessment of chemicals such as 

ATMD that show primarily portal-of-entry effects (irritation, corrosion). Regulation of hazard on 

such effects is considered protective of any systemic effects that might occur and is consistent 

with previous decisions made in OPP for chemicals whose effects are primarily portal-of-entry 

effects. 
Page 19 of 103

Table 1: Endpoints for use in ATMD Drinking Water Assessments 

Exposure 

Scenario 

Point of 

Departure 

Uncertainty 

Factors 

RfD. Level of 

concern for risk 

assessment 

Study and 

Toxicological 

Effects 

Acute and Chronic 

Dietary 

0.4 mg/kg/day 100 (10x 

interspecies 

extrapolation, 10x 

intra-species 

variation) 

aRfD=aPAD= 0.004 

mg/kg/day 

cRfD=cPAD= 0.004 

mg/kg/day 

90-day oral toxicity 

study in rodents 

(MRID 49092801) 

LOAEL = 1.5 

mg/kg/day, based on 

decrease in body 

weight gain and food 

consumption in 

males and 

histopathology 

changes in the male 

and female 

mesenteric lymph 

node, spleen, bone 

marrow (sternum) 

and trachea 

 

3.2.1  FQPA Considerations  

 The database for FQPA assessment of ATMD currently consists of the OECD combined 

repeat dose reproductive/ developmental study on the representative compound that is a mixture 

of C8-C18 primary amines derived from oleochemicals. The Executive Summary for the study is 

included in Appendix B. 

 There was no increased susceptibility to the offspring of rats following prenatal and postnatal exposure in the OECD 422 reproductive/developmental screening study. Decreased pup 

body weight was observed at 40 and 80 mg/kg/day where maternal/paternal toxicity was 

manifested as microscopic lesions in the stomach, jejunum, thymus, and lymph nodes at 20, 40, 

and 80 mg/kg/day. Since the rat reproduction/developmental study identified a clear NOAEL of 

20 mg/kg/day for offspring effects, and the parental NOAEL for stomach/jejunum/thymus/lymph 

node lesions for the dietary risk assessment is protective of the offspring effects, there are no 

residual concerns for toxicity. 

 There are also no residual uncertainties identified in the exposure databases. Dietary 

exposure assessments are considered to be conservative. The drinking water assessment is not 
Page 20 of 103

likely to underestimate exposure to any subpopulation, including those comprised of infants and 

children. Therefore, the FQPA factor can be reduced to 1x. 

 The total uncertainty factor for derivation of the RfD is therefore 100. 

3.3   Dietary Assessment

 ATMD as a group have a currently registered use pattern as antimicrobial pesticides in 

industrial process water systems (oilfield injection water systems, industrial recirculating water 

cooling towers, and well completion and workover fluids). 

 For the registration action discussed in this risk assessment, the proposed use of ATMD 

to control bio-fouling in once-through and recirculating cooling towers constitutes a new use 

where human exposure through drinking water can be expected to occur. Thus a risk assessment 

from exposure to ATMD in drinking water is necessary. The registrant has proposed the NOAEL 

of 0.4 mg/kg/day from the submitted 90-day oral toxicity study on ATMD as the endpoint for 

use in the risk assessment. This value was used for deriving the acute and chronic reference dose 

(aRfD and cRfD respectively) to assess risks from exposure to ATMD in drinking water for this 

assessment. 

3.2.2 Dietary Exposure and Risk Analysis

 Initially, surface water concentrations of ATMD from the proposed use were estimated 

based on results from the General Population and Ecological Exposure from Industrial Releases 

Module of the Exposure and Fate Assessment Screening Tool (E-FAST). Results of this analysis 

(shown in Table 2 below) shows the surface water concentrations based the lowest 30 

consecutive day average flow that occurs [on average] once every 5 years (30Q5) and harmonic 

mean (i.e., inverse mean of reciprocal daily arithmetic mean flow values) for the 10th and 50th

percentile distributions of stream flow to plant flow assuming no removal of active ingredient 

prior to its discharge in effluent. The 10th percentile exposure represents a high-end scenario 

where plant flow contributes considerable volume relative to the stream flow. The 50th

percentile exposure represents a median or more typical ratio of stream flow to plant flow. For 

completeness, an estimated drinking water concentration (EDWC) of 42.5 ppb was added to 

represent the worst case end-of-pipe scenario. 
Page 21 of 103

 For the determination of drinking water exposures to humans, the surface water 

concentration from E-FAST based on the 30Q5 flow value was used to represent acute exposure 

and the harmonic mean flow value was used to represent chronic exposure. 

 Using the surface water concentrations and end of pipe concentration shown in Table 2, 

acute and chronic dietary (drinking water only) human exposures were calculated for ATMD 

using the Dietary Exposure Evaluation Model software with the Food Commodity Intake 

Database (DEEM-FCID) Version 3.16. This software uses 2003-2008 food consumption data 

from the U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition 

Examination Survey, What We Eat in America, (NHANES/WWEIA). The data are based on the 

reported consumption of more than 20,000 individuals over two non-consecutive survey days. 

For chronic exposure assessment, consumption data are averaged for the entire U.S. population 

and within population subgroups. However, for acute exposure assessment, consumption data 

are retained as individual consumption events. Based on analysis of the 2003-2008 WWEIA 

consumption data, which took into account dietary patterns and survey respondents, AD 

concluded that it is most appropriate to report exposures and risks for the following population 

subgroups: the general U.S. population, all infants (<1 year old), children 1-2, children 3-5, 

children 6-12, youth 13-19, adults 20-49, females 13-49, and adults 50-99 years old. 

 For a chronic dietary (drinking water in this case) exposure assessment, an estimate of the 

residue level in each food or food-form on the food commodity residue list is multiplied by the 

average daily consumption estimate for that food/food form to produce a residue intake estimate. 

The resulting residue intake estimate for each food/food form is summed with the residue intake 

estimates for all other food/food forms on the commodity residue list to arrive at the total 

average estimated exposure. Exposure is expressed in mg/kg body weight/day and as a percent 

of the reference dose (acute and chronic RfD). This procedure is performed for each population 

subgroup. 

 For an acute exposure assessment, individual one-day food consumption data are used on 

an individual-by-individual basis. The reported consumption amounts of each food item can be 

multiplied by a residue point estimate and summed to obtain a total daily pesticide exposure for a 

deterministic exposure assessment, or “matched” in multiple random pairings with residue values 

and then summed in a probabilistic assessment. The resulting distribution of exposures is 

expressed as a percentage of the RfD on both a user (i.e., only those who reported eating relevant 

commodities/food forms) and a per-capita (i.e., those who reported eating the relevant 

commodities as well as those who did not) basis. In accordance with policy, per capita exposure 

and risk are reported for analyses performed at all levels of refinement. 

 Note that water concentrations were incorporated in DEEM-FCID into the food 

categories “water, direct, all sources” and “water, indirect, all sources” for the purposes of this 

assessment. 
Page 22 of 103

Table 2: Estimated Drinking Water Concentrations (EDWCs) of ATMD for Surface 

Water using the E-FAST Model 

Drinking Water 

Source 

Scenario Acute Concentration 

based on 30Q5 Stream 

Flow Distribution 

(μg/L) 

Chronic Concentration based 

on Harmonic Mean Stream 

Flow Distribution 

(μg/L) 

Surface Water 

(E-FAST) 

End-of-pipe 42.5 42.5 

Once through cooling system 

0% removal 

10th percentile concentration 

18.25 4.62 

Once through cooling syatem 

0% removal 

50th percentile concentration 

0.22 0.11 

Recirculating cooling tower 

0% removal 

10th percentile concentration 

8.39 2.12 

Recirculating cooling tower 

0% removal 

50th percentile concentration 

0.098* 0.049* 

* These scenarios were not modeled with DEEM because exposures with higher Estimated Drinking Water 

Concentrations (EDWCs) produced negligible risk estimates. 

 Results of the exposure and risk analyses for the proposed ATMD use are presented 

below in Tables 3 through 6. The highest exposed sub-population for each analysis is bolded. 

Table 3: Summary of Acute and Chronic Dietary Exposure and Risk Analyses for ATMD 

(End-of-pipe water concentration) 

Population Subgroup 

Acute Chronic 

Estimated 

Exposure 

(95th

Percentile) 

(mg/kg/day) 

Estimated 

Risk, % aRfD 

MOE 

(LOC = 

100) 

Estimated 

Exposure 

(average) 

(mg/kg/day) 

Estimated 

Risk, % cRfD 

MOE 

(LOC = 

100) 

U.S. Population 0.002317 58 170 0.000890 22 450 

All infants 0.007258 180 55 0.002295 57 170 

Children 1-2 yrs 0.003574 89 110 0.001284 32 310 

Children 3-5 yrs 0.002900 72 140 0.001082 27 370 

Children 6-12 yrs 0.00216 55 180 0.000780 20 510 
Page 23 of 103

Population Subgroup 

Acute Chronic 

Estimated 

Exposure 

(95th

Percentile) 

(mg/kg/day) 

Estimated 

Risk, % aRfD 

MOE 

(LOC = 

100) 

Estimated 

Exposure 

(average) 

(mg/kg/day) 

Estimated 

Risk, % cRfD 

MOE 

(LOC = 

100) 

Youth 13-19 yrs 0.001930 48 210 0.000649 16 620 

Adults 20-49 yrs 0.002280 57 180 0.000888 22 450 

Adults 50+ yrs 0.002031 51 200 0.000878 22 460 

Females 13-49 yrs 0.002313 58 170 0.000885 22 450 

Table 4: Summary of Acute and Chronic Dietary Exposure and Risk Analyses for ATMD 

(Once through cooling system, 0% removal, 10th percentile ratio of stream flow to plant 

flow) 

Population Subgroup 

Acute Chronic 

Estimated 

Exposure 

(95th

Percentile) 

(mg/kg/day) 

Estimated 

Risk, % aRfD 

MOE 

(LOC = 

100) 

Estimated 

Exposure 

(average) 

(mg/kg/day) 

Estimated 

Risk, % cRfD 

MOE 

(LOC = 

100) 

U.S. Population 0.000995 25 400 0.000097 2.4 4100 

All infants 0.003117 78 130 0.000249 6.2 1600 

Children 1-2 yrs 0.001535 38 260 0.000140 3.5 2900 

Children 3-5 yrs 0.001245 31 320 0.000118 2.9 3400 

Children 6-12 yrs 0.000951 24 420 0.000085 2.1 4700 

Youth 13-19 yrs 0.000829 21 480 0.000071 1.8 5600 

Adults 20-49 yrs 0.000979 24 410 0.000097 2.4 4100 

Adults 50+ yrs 0.000872 22 460 0.000095 2.4 4200 

Females 13-49 yrs 0.000993 25 400 0.000096 2.4 4200 
Page 24 of 103

Table 5: Summary of Acute and Chronic Dietary Exposure and Risk Analyses for ATMD 

(Once through cooling system, 0% removal, 50th percentile ratio of stream flow to plant 

flow) 

Population Subgroup 

Acute Chronic 

Estimated 

Exposure 

(95th

Percentile) 

(mg/kg/day) 

Estimated 

Risk, % aRfD 

MOE 

(LOC = 

100) 

Estimated 

Exposure 

(average) 

(mg/kg/day) 

Estimated 

Risk, % cRfD 

MOE 

(LOC = 

100) 

U.S. Population 0.000001 <1 400000 0.000000 <1 NA 

All infants 0.000004 <1 100000 0.000001 <1 400000 

Children 1-2 yrs 0.000002 <1 200000 0.000000 <1 NA 

Children 3-5 yrs 0.000002 <1 200000 0.000000 <1 NA 

Children 6-12 yrs 0.000001 <1 400000 0.000000 <1 NA 

Youth 13-19 yrs 0.000001 <1 400000 0.000000 <1 NA 

Adults 20-49 yrs 0.000001 <1 400000 0.000000 <1 NA 

Adults 50+ yrs 0.000001 <1 400000 0.000000 <1 NA 

Females 13-49 yrs 0.000001 <1 400000 0.000000 <1 NA 

Table 6: Summary of Acute and Chronic Dietary Exposure and Risk Analyses for ATMD 

(Recirculating cooling tower, 0% removal, 10th percentile ratio of stream flow to plant 

flow) 

Population Subgroup 

Acute Chronic 

Estimated 

Exposure 

(95th

Percentile) 

(mg/kg/day) 

Estimated 

Risk, % aRfD 

MOE 

(LOC = 

100) 

Estimated 

Exposure 

(average) 

(mg/kg/day) 

Estimated 

Risk, % cRfD 

MOE 

(LOC = 

100) 

U.S. Population 0.000457 11 880 0.000044 1.1 9100 

All infants 0.001433 36 280 0.000114 2.9 3500 

Children 1-2 yrs 0.000705 18 570 0.000064 1.6 6300 

Children 3-5 yrs 0.000572 14 700 0.000054 1.3 7400 
Page 25 of 103

Population Subgroup 

Acute Chronic 

Estimated 

Exposure 

(95th

Percentile) 

(mg/kg/day) 

Estimated 

Risk, % aRfD 

MOE 

(LOC = 

100) 

Estimated 

Exposure 

(average) 

(mg/kg/day) 

Estimated 

Risk, % cRfD 

MOE 

(LOC = 

100) 

Children 6-12 yrs 0.000437 11 920 0.000039 1.0 10000 

Youth 13-19 yrs 0.000381 10 1100 0.000032 <1 13000 

Adults 20-49 yrs 0.000450 11 890 0.000044 1.1 9100 

Adults 50+ yrs 0.000401 10 1000 0.000044 1.1 9100 

Females 13-49 yrs 0.000457 11 880 0.000044 1.1 9100 

 The above calculations of exposure and risk for ATMD represent conservative scenarios 

for both the once-through and recirculating cooling tower uses, because of the following 

assumptions: (1) none of the chemical is assumed to be removed from water; (2) there is no 

sorption (and hence removal) of the chemical to solids in the water; (3) the 10th percentile of 

exposure represents a conservative estimate of drinking water exposures. 

 One scenario analyzed above showed a risk of concern. Using the end-of-pipe 

concentration of 42.5 ppb, a MOE < 100 was calculated for all infants for acute exposure at the 

95th percentile. The Agency does not consider this to be a likely exposure scenario since the 

label states that this is for use in non-potable waters and the end of pipe concentration does not 

account for dilution, sorption or degradation. No mitigation measures are needed for this 

exposure scenario. 

3.3 Residential Non­Dietary Assessment

 Because the ATMD is proposed for use only in non-potable industrial water systems, 

residential exposures are not anticipated. 
Page 26 of 103

3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures

 In order for a pesticide registration to continue, it must be shown that the use does not 

result in “unreasonable adverse effects on the environment.” Section 2 (bb) of FIFRA defines 

this term to include “a human dietary risk from residues that result from a use of a pesticide in or 

on any food inconsistent with standard under section 408...” of FFDCA. Consequently, even 

though no pesticide tolerances have been established for ATMD the standards of FQPA must 

still be met. As mandated by the FQPA amendments to FIFRA and the Federal Food, Drug and 

Cosmetic Act (FFDCA), the Agency must consider total aggregate exposure from food, drinking 

water and residential sources of exposure to ATMD. 

 Acute aggregate dietary assessment would include both acute dietary and drinking water 

exposures. Chronic aggregate dietary assessment would include chronic exposure through diet 

and drinking water. For the proposed new use of ATMD, there are potential exposures in 

drinking water. There are no exposures in food. An aggregate assessment is therefore not 

necessary, and the calculated drinking water risks shown above represent the total exposure and 

risk for ATMD from the proposed use. 

3.4.2 Cumulative Exposures

 With respect to cumulative exposure, unlike other pesticides for which EPA has followed 

a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a 

common mechanism of toxicity finding as to ATMD and any other substances and ATMD does 

not appear to produce a toxic metabolite produced by other substances. For the purposes of this 

preliminary risk assessment, therefore, EPA has not assumed that ATMD has a common 

mechanism of toxicity with other substances. For information regarding EPA’s efforts to 

determine which chemicals have a common mechanism of toxicity and to evaluate the 

cumulative effects of such chemicals, see http://www.epa.gov/pesticides/cumulative/. 

3.5 Occupational Exposure

 There is a potential for occupational dermal and inhalation exposure during the mixing 

and loading of ATMD into industrial cooling water systems. This potential is minimal; however, 
Page 27 of 103

if closed loading and delivery systems are used. The directions on the proposed product label 

suggest that ATMD will be applied using closed loading systems although the language is not 

clear because it specifies "closed delivery systems" rather than "closed loading and delivery 

systems". If the label could be revised to specify "closed loading and delivery systems" then it 

could be assumed that occupational exposures would be minimal and it would not be necessary 

to conduct a risk assessment to quantify these exposures. 

Post application inhalation exposures to ATMD as a vapor is expected to be minimal because the 

vapor pressure of ATMD is less than 1 x 10-4 mm Hg, which is the cutoff that EPA typically uses 

to determine if inhalation exposure to vapors needs to be assessed. Post application inhalation 

exposure to cooling water aerosols containing ATMD is also expected to be minimal because of 

the low application rate of 4.0 ppm. 

3.7 Human Health Risk Characterization

 The assessment of exposure to humans from the proposed use of ATMD relies upon 

estimates of surface water concentrations as determined in the E-FAST model. These surface 

water concentrations are considered conservative estimates of exposure, as there is the 

assumption of no sorption to solids contained within water and that there is no removal of 

ATMD through wastewater treatment. Using the surface water concentration estimates, the 

DEEM-FCID model is used to calculate human exposure and risk to identified subpopulations of 

concern. The calculation of risk is also based on the use of a conservative NOAEL value of 0.4 

mg/kg/day from a 90-day oral toxicity study in rats, to which a standard uncertainty factor of 100 

(10x for species extrapolation, 10x for intra-species variation) is applied. This adds additional 

conservatism to the risk assessment. 

 The use of these conservative assumptions and the resulting lack of concern for risk to 

humans are considered to be adequate in addressing uncertainties in human hazard and exposure 

for this risk assessment. Any refinement to the assessment would not likely result in any risks of 

concern, considering the already large margins of exposure identified in the present risk 

assessment. There would need to be considerably higher human exposure and/or a considerably 

lower NOAEL value for ATMD for there to be risks of concern in this assessment. Higher 

human exposure may arise through additional uses of ATMD, and lower NOAEL values from 

future review of the hazard database for ATMD (including new data). 
Page 28 of 103

3.0 ECOLOGICAL RISK ASSESSMENT

 This section presents the ecological effects data and exposure assessment for ATMD 

conducted by the Agency. The exposure estimates and toxicity effects data are integrated in 

order to provide estimates of risks to ecological organisms. The risks from the proposed cooling 

water uses of ATMD are then characterized taking into consideration the agency’s estimates of 

risk and other weights of evidence both quantitative and qualitative (e.g., whole effluent toxicity 

testing, site specific risk modeling submitted by the registrant, dilution factors, assumptions and 

limitations). 

4.1 Selected Ecological Toxicity Endpoints

 Ecological effects data are used as measures of direct and indirect effects to aquatic and 

terrestrial organisms. Acute and chronic toxicity data from registrant-submitted studies 

conducted in accordance with the 850 OCSPSP Harmonized Test Guidelines, along with values 

modeled using interspecies correlation estimation methods, and acute-to-chronic ratios (ACR) 

were used to evaluate the potential direct and indirect effects of ATMD to plants and animals. 

All data requirements and available ecotoxicity endpoints from studies submitted by registrants 

are tabulated in Appendix C. Additionally, as described in Appendix C, Web-ICE (EPA 2013) 

has been used to predict the acute toxicity to the fathead minnow. ACRs (EPA 2010) also have 

been extrapolated to estimate chronic No Observable Adverse Effects Concentrations (NOAECs) 

for freshwater fish and estuarine/marine fish and invertebrates. For each receptor group and 

measure of effect, OPP uses the most sensitive of these endpoints for assessing risk. The 

endpoints selected for the risk assessment for ATMD are provided in Table 7. 

Table 7: Effects Endpoints Selected for Assessing Ecological Risks to ATMD 

Receptor 

Group Surrogate Species Risk Scenario Toxicity Endpoint Reference 

Freshwater fish Rainbow trout Acute 96-h LC50 = 120 μg ai/L 41786606 

Chronic NOAEC = 4 μg ai/La See Appendix C 

Freshwater 

invertebrates 

Mollusk Acute 48-h LC50 = 19 μg ai/L 

Use of estuarine/ 

marine mollusk value 

as a surrogate 

Water flea Acute 48-h EC50 = 51 μg ai/L 41786602 

Chronic NOAEC = 16 μg ai/L 49040208 

Freshwater benthic 

invertebrates 

Midge Subchronic 10-day EC50 = 188 mg ai/kg 

sediment 49040211 

Amphipod Subchronic Data gap 

Estuarine/marine fish Atlantic silverside Acute 96-h LC50 = 155 μg ai/L 41786604 
Page 29 of 103

Receptor 

Group Surrogate Species Risk Scenario Toxicity Endpoint Reference 

Chronic NOAEC = 5 μg ai/Lb See Appendix C 

Estuarine/marine 

invertebrates 

Mollusk Acute 48-h EC50 = 19 μg ai/L 41786603 

Shrimp Acute 96-h LC50 = 61 μg ai/L 41786605 

Chronic NOAEC = 19 μg ai/Lc See Appendix C 

Estuarine/marine 

benthic invertebrates Chironomid sp. Subchronic 10-day EC50 = 303 mg ai/kg 

sediment 49040212 

Algae Green algae Nonlisted EC50 = 5.2 μg ai/L 49040216 Listed NOAEC = 2.4 μg ai/L 

Aquatic vascular 

plants Duckweed Nonlisted EC50 = 123 μg ai/L 49040213 Listed NOAEC = 20 μg ai/L 

Birds Mallard duck Acute LD50 = 0.24 mg/kg-bw 47013023 

a

 The rainbow trout was the most acutely sensitive fish species tested but no chronic data are available for this 

species; therefore, a chronic NOAEC was estimated for the trout. The chronic value was extrapolated using an ACR 

(EPA 2010) of 29 (see Appendix C) as determined by using the fathead minnow acute LC50 (328 μg ai/L as 

predicted from Web-ICE; EPA 2013, see Appendix C) divided by the fathead minnow chronic NOAEC (11 μg 

ai/L), and then applying this ratio to the acute rainbow trout LC50 (120 μg ai/L). 

b

 The chronic NOAEC is extrapolated using the ACR (29) for freshwater fish (see footnote a) and applying this ratio 

to the acute LC50 of 155 μg ai/L for the Atlantic silverside; the extrapolation assumes a common chronic mode of 

action for freshwater and estuarine/marine fish. 

c The chronic NOAEC is extrapolated from the ACR (3) for freshwater invertebrates (D. magna acute LC50 = 51 μg 

ai/L, divided by the D. magna chronic NOAEC = 16 μg ai/L) and applying this ratio to the acute toxicity for the 

estuarine/marine crustacean (mysid shrimp LC50 = 61 μg ai/L); the extrapolation assumes a common chronic mode 

of action for freshwater and estuarine/marine crustaceans. 

4.1.1 Effects to Wastewater Treatment Plant Microorganisms

 An Activated Sludge Respiration Inhibition (ASRI) study is used to determine the 

potential of a chemical substance to directly harm the microorganisms present in the activated 

sludge treatment process at conventional wastewater treatment facilities. Results from an ASRI 

study are used to determine the potential risk of inhibiting activated sludge microorganisms, 

thereby allowing pollutants to pass through to the environment as a result of untreated or 

partially treated wastewater. ASRI test results are also used to determine what type of 

wastewater treatment plant biodegradation testing would be appropriate, such as a ready 

biodegradability test or an activated sludge biodegradation simulation test. 

 The Activated Sludge Respiration Inhibition study (Schaefer E and A Ponizovsky (2012); 

MRID 49040218; see Appendix A for complete citation) provides supplemental data but is not 

acceptable because the confidence bounds for the IC50 are too wide. For the test substance, 

ATMD, the reported IC50 was 22 mg/l with a 95 % confidence interval of 10-30 mg/l. 

Additional sampling at concentrations of the test substance between the 95% confidence bounds 

of 10 and 30 mg/l would be needed to provide a more accurate determination of the IC50. The 

percent respiration inhibition measured ranged from -1.5 % at 10 mg/l to 77.8 % at 30 mg/l with 
Page 30 of 103

no concentrations measured in between. As a result, it cannot be concluded with reasonable 

confidence that the activated sludge IC50 is 22 mg/L. 

4.2 Summary of Ecological Exposure Assessment Approach

 Three basic approaches were used to estimate potential risks from exposures of 

ecological organisms to ATMD: a quantitative approach, a semi-quantitative approach, and a 

qualitative approach. A quantitative approach was used to estimate exposures to freshwater fish 

and invertebrates in the surface water column and to estimate exposures to freshwater benthicdwelling organisms. A semi-quantitative approach was used to estimate exposures to 

estuarine/marine organisms in the surface water column and to estimate exposures to 

estuarine/marine benthic-dwelling organisms. A qualitative approach was used for estimating 

exposures to piscivorus birds and mammals. 

 Based on information from the MEXEL 432/0 product label, all estimates of ecological 

risk are based on maintenance of 2.5 ppm residual Mexel 432/0. The concentration of the active 

ingredient in the product is 1.7 percent; based on maintenance of 2.5 ppm product residual, this 

corresponds to 42.5 ug/L ATMD. 

 The exposure scenarios that form the basis of this ecological risk assessment include 

exposures from releases to surface water from: 

 large-size recirculating cooling towers; 

 moderate-size recirculating cooling towers; and 

 once-through cooling systems. 

For recirculating cooling towers, exposures from releases to surface water were estimated with 

and without wastewater treatment. Exposures based on no wastewater treatment assumed no 

removal of the active ingredient. Exposures based on wastewater treatment were estimated 

assuming 71 percent removal during wastewater treatment and 92 percent removal during 

wastewater treatment. The assumption of 71 percent removal during wastewater treatment is 

based on removal expected from sorption to activated sludge as a result of treatment in the 

activated sludge basin for 4 hours. The assumption of 92 percent removal during wastewater 

treatment is based on removal expected from sorption to activated sludge as a result of treatment 

in the activated sludge basin for 6 hours. The range of 4 to 6 hours assumed for treatment in an 

activated sludge basin is considered typical for activated sludge treatment in conventional 

wastewater treatment systems. These estimates of percent removal are based on experimental 

results reported in the activated sludge sorption isotherm study submitted by the registrant and 

are based on sorption of the active ingredient by activated sludge after 4 and 6 hours under 
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conditions that simulate an activated sludge basin (MRID 49040205; Schaefer, E and A 

Ponizovsky (2012); (See Appendix A for complete citation)). 

 For once-through cooling systems, it was assumed that no treatment of effluent (i.e., no 

removal of active ingredient) occurs prior to discharge to surface water. 

 The general methodology used to estimate water column and sediment exposures to 

ecological organisms from release of ATMD from once-through and recirculating cooling towers 

in presented in Appendix E. 

4.2.1 EPA’s Estimation of Exposure of Freshwater Fish and Invertebrates to ATMD

in the Water Column

 The probabilistic dilution model (PDM) option of The General Population and Ecological 

Exposures for Industrial Releases module (hereinafter referred to as the Industrial Releases 

Module) of E-FAST was used to estimate magnitude of exposure of aquatic organisms in the 

surface water column to ATMD, the active ingredient present at 1.7 percent in the product, 

Mexel 432/0. Key input parameters needed to run this module include the environmental release 

to surface water in kg/site/day, percent removal of active ingredient during wastewater treatment, 

and concentrations of concern for aquatic organisms. Model outputs are expressed as days per 

year of exceedance of concentrations of concern for aquatic organisms. Estimates of exposure 

were developed for both a high-end scenario (i.e., 10th percentile of the distribution of the ratio of 

7Q10 stream flows to plant flows) and for an average case scenario (i.e., the median of the 

distribution of the ratio of 7Q10 stream flows to plant flows). The 7Q10 is the lowest 7 

consecutive-day stream flow over a 10-year period. A detailed discussion of the PDM approach 

is presented in Appendix D. A detailed discussion of the methodology for estimating potential 

risks from exposure of aquatic organisms to ATMD is presented in Appendix D. 

 The following information appears on the proposed MEXEL 432/0 product label: 

“MEXEL 432/0 is to be used for the control of biofouling, including zebra mussels and clams in 

once-through cooling and cooling tower circuits with closed delivery systems for non-potable 

industrial freshwater and sea water systems. The product may be applied to maintain clean 

systems or to treat systems that are already fouled. Normal frequency of treatment is once per 

day or as needed to maintain control. The amount of the daily dose is determined by the circuit 

characteristics. The daily dose is 4.0 ppm for 30 minutes with a residual concentration of 2.5 

ppm.”. The concentration of active ingredient in the product is reported on the product label to 

be 1.7 percent; based on maintenance of 2.5 ppm product residual, this corresponds to 42.5 ug/L 

ATMD. 
Page 32 of 103

 All estimates of ecological risk are based on maintenance of 2.5 ppm residual MEXEL 

432/0 throughout a 24-hour period. Although the product label indicates that the normal 

frequency of treatment is once per day, it also states that the product can be applied as needed to 

maintain control and that the amount of the daily dose is determined by the circuit 

characteristics. As a result, the label specifies no upper limit on the frequency of treatment on a 

daily basis. For the purpose of estimating exposures to ecological organisms, the Agency 

assumed that a 2.5 ppm residual is maintained throughout a 24-hour period. Under 

circumstances in which only a single dose would be applied for 30 minutes daily and a product 

residual of 2.5 ppm would be maintained throughout a 24-hour period, these estimates of 

exposure would represent peak exposures of ecological organisms to ATMD used in cooling 

towers. 

 In site-specific modeling results submitted by Mexel to the Agency (MRID 49040220; 

Ackerman, D, F. Ghillebaert, and M.W. Glass, 2013; (See Appendix E for the complete 

citation)), the registrant estimated a daily environmental loading based on the assumption that a 

30-minute dose of product, corresponding to a maintenance dose of product of 2.5 ppm (i.e., 42.5 

ug/L ATMD), would be maintained over a 24-hour period. Normalizing an environmental 

loading over a 24-hour period could considerably underestimate potential exposure, especially 

given that the label does not provide an upper limit on the frequency of application of the 

product on a daily basis and that the label specifies maintenance of a 2.5 ppm residual of 

MEXEL 432/0. 

4.2.2 EPA’s Estimation of Exposure of Freshwater Benthic Invertebrates to ATMD in

Sediments

 Estimates of potential exposure to freshwater benthic invertebrates were derived from 

estimates of concentrations of ATMD in freshwater benthic sediments. Estimates of 

concentrations of ATMD in sediment were derived from data on leaching adsorption-desorption 

to soil and surface water concentrations estimated from the Industrial Releases module of EFAST. The methodology used to estimate concentrations of ATMD in freshwater and sediments 

are presented in Appendix F. Table 8 presents estimates of concentrations of ATMD in 

freshwater benthic sediments for once-through cooling systems, large-size cooling towers, and 

moderate-size cooling towers based on 10th and 50th percentile 7Q10 surface water 

concentrations estimated from the Industrial Releases module of E-FAST. 
Page 33 of 103

Table 8: Estimated Concentrations of ATMD in Freshwater Benthic Sediment Based on 

10th and 50th Percentile Surface Water Concentrations Estimated from the General 

Population Exposures and Industrial Releases Module of E-FAST 

Cooling Tower Scenario 10th Percentile 

7Q10 Surface 

Water 

Concentration 

(ug/L) 

Sediment 

Concentration 

based on 10th

Percentile 7Q10 

A

(mg/kgsediment) 

50th Percentile 

7Q10 Surface 

Water 

Concentration 

(ug/L) 

Sediment 

Concentration 

based on 50th

Percentile 7Q10A

(mg/kgsediment) 

Once-Through Cooling Tower 

(2 MGD) with No Treatment 

30.98 1053.8 0.31 10.54 

Large-Size Recirculating 

Cooling Tower (144 MGD) 

with No Treatment14.23 484 0.14 4.76 

Large-Size Recirculating 

Cooling Tower with 71 Percent 

Removal During Wastewater 

Treatment 

4.21 143.2 0.042 1.44 

Large-Size Recirculating 

Cooling Tower with 92 Percent 

Removal During Wastewater 

Treatment 

1.16 39.5 0.012 0.41 

Moderate-Size Recirculating 

Cooling Tower (2.88 MGD) 

with No Treatment 

0.28 9.52 0.0028 0.095 

Moderate-Size Recirculating 

Cooling Tower with 71 Percent 

Removal During Wastewater 

Treatment 

0.081 2.77 0.00082 0.028 

Moderate-Size Recirculating 

Cooling Tower with 92 Percent 

Removal During Wastewater 

Treatment 

0.023 0.78 0.00023 0.0078 

A Sediment concentration was estimated using the relationship between water concentration and sediment/soil Kf. 

The method is discussed in Appendix. 

4.2.3 EPA’s Estimation of Exposure of Estuarine/Marine Fish and Invertebrates to

ATMD in the Water Column

 Since estuarine and marine water bodies are not flowing water bodies and have no stream 

flows associated with them, the probabilistic dilution model (PDM) option of The General 

Population and Ecological Exposures for Industrial Releases module (hereinafter referred to as 

the Industrial Releases Module) of the Exposure and Fate Assessment Screening Tool (E-FAST) 

is not an appropriate tool for estimating exposures to estuarine/marine fish and invertebrates in 
Page 34 of 103

the water column. Therefore, the worst case scenario of once-through cooling systems with no 

treatment and an associated concentration of AMTD at the discharge point (42.5 μg ai/L) are 

used as an upper-bound scenario to determine if estuarine/marine animals and plants might 

potentially be at risk. Based on this scenario, for those receptor groups for which risk quotients 

are exceeded, dilution factors can be calculated to determine the concentration of concern below 

which exposure would not be likely to be of concern for listed and nonlisted estuarine fish and 

invertebrates (e.g., crustaceans, gastropods) and for algae. 

4.2.4 EPA’s Estimation of Exposure of Estuarine/Marine Benthic Invertebrates to

ATMD in Sediments

 Exposure of estuarine/marine benthic invertebrates to ATMD is assumed to be primarily 

from ATMD present in benthic sediments., As with estuarine/marine water column 

concentrations, an upper bound estimate of exposure based on a residual concentration of ATMD 

at the discharge point (42.5 μg ai/L) is used to derive concentrations of ATMD in sediments and 

to determine if estuarine/marine benthic organisms might potentially be at risk. For this 

scenario, the estimated estuarine sediment concentration is 1445.7 mg ai/kg sediment. 

4.2.5 EPA’s Estimation of Exposures to Piscivorous Birds and Mammals

 Upper bound exposures to piscivorus birds were based on an end-of-pipe discharge 

concentration of 42.5 ug/L ATMD and a whole-fish bioconcentration factor of 378-388X. 

4.2.6 Mexel’s Estimation of Exposure to ATMD Released from Cooling Towers and

Once­Through Industrial Cooling Water Systems

 In a non-guideline study submitted to the Agency (Ackerman, D, F Ghillebaert, and 

M.W. Glass, 2013: MRID 49040220), Mexel used two modeling approaches to estimate 

exposures and risks to aquatic organisms downstream of two power plants. The first modeling 

approach used the site-specific option of the General Population Exposures and Industrial 

Releases module of E-FAST to provide screening level estimates of exposures to aquatic 

organisms and the second approach used the higher tier CE-QUAL-W2 model to provide more 

refined estimates of exposures to aquatic organisms. Mexel considered the two power plants 

they selected for modeling to be atypical and to have the greatest impact. One power plant, the 

Hammond Power Plant near Rome, Georgia was selected to be representative of the distribution 

of facilities in Standard Industrial Classification Code (SIC) 4911 (i.e., steam electric power 
Page 35 of 103

plants); Mexel reports that this power plant was in the 95th percentile of all power plant 

discharges and that its discharge flow of 2082 million liters per day (MLD) was approximately 

equal to the 7Q10 flow of the Coosa River downstream of the plant (i.e., 2927 MLD), 

representing a realistic case where the dilutive capacity of the receiving water would be at a 

minimum. The second power plant, the Crockett Power Plant near Girvin, TX was selected by 

Mexel to investigate the impacts of using ATMD at a smaller power plant on a smaller stream, 

the Pecos River; Mexel reports that the discharge flow from this power plant, 5.29 MLD was in 

the 37th percentile of the distribution of power plants and that the 7Q10 flow of the Pecos river 

downstream of the plant is 5.24 MLD (mean stream flow is 1674 MLD). 

 Mexel assumed that the product would be applied over a 30-minute period to achieve a 

maintenance concentration of ATMD of 42.5 ug/L. Mexel estimated that this concentration 

would result in 1.04 kg/day being released to surface water from the Hammond Power Plant and 

0.00468 kg/day being released to surface water from the Crockett Power Plant. The loadings in 

kg/site/day used as inputs to the Industrial Releases model were normalized over a 24-hour 

period and reduced to reflect a 44 percent “demand” that was representative of the range of 

“immediate demands” from 21 to 86% for the formulated end use product (EP). 

 EPA’s interpretation of these modeling results is discussed in the Risk Characterization 

section of this risk assessment. 

4.3 Estimation of Risks to Aquatic Organisms

 Risk estimation integrates the results of the exposure and ecotoxicity data to evaluate the 

likelihood of adverse ecological effects. There are generally two approaches used in assessing 

risks from industrial process and water systems, a risk quotient (RQ) method and a probabilistic 

method. These two basic approaches are discussed in Appendix D. The probabilistic approach 

was used to estimate potential risks to freshwater organisms. The risk quotient method was used 

to estimate potential risks to both freshwater and estuarine/marine benthic invertebrates, and to 

estuarine/marine organisms. In addition, for marine/estuarine organisms, dilution factors that 

would be needed to mitigate exceedance of concentrations of concern were estimated. A 

qualitative approach was used to estimate potential risks to piscivorus birds. 

4.3.1 Estimation of Risks to Freshwater Organisms Exposed to ATMD in the Water

Column

 Potential risks to freshwater aquatic organisms from exposure to ATMD were estimated 

for the following scenarios: 
Page 36 of 103

 moderate-size recirculating cooling towers (2000 gallons per minute or 2.88 

million gallons per day (MGD) recirculation rate); 

 large-size recirculating cooling towers (100,000 gallons per minute or 144 million 

gallons per day); and 

 once-through cooling systems (intake flows of 2, 20, 50, and 100 MGD) 

Moderate-Size Recirculating Cooling Towers

 Tables 9 through 11 present estimates of numbers of days per year of exceedance of 

concentrations of concern (COCs) for freshwater organisms downstream of moderate-size 

recirculating cooling towers. Table 9 presents estimates of the number of days per year of 

exceedance of acute COCs for freshwater organisms, Table 10 presents estimates of the number 

of days per year of exceedance of COCs for endangered/listed freshwater organisms, and Table 

11 presents estimates of the number of days per year of exceedance of chronic COCs for 

freshwater fish and invertebrates. 

Table 9: Estimates of Numbers of Day Per Year of Exceedance of Acute COCs for 

Freshwater Organisms Downstream of Moderate-Size Recirculating Cooling Towers 

(0.0029 kg/site/day release of ATMD before treatment based on 2.5 ppm residual of 

product (42.5 ug/L active ingredient)) 

Acute COCsA

Number of Days per Year of Exceedance of COCs 

No Treatment (0% 

Removal) 

71% Removal During 

WWT 

92% Removal During 

WWT 

High-end Average High-end Average High-end Average 

123 ppb (Non-listed 

aquatic vascular plants) 0 0 0 0 0 0 

60 ppb (acute freshwater 

fish 1 0 0 0 0 0 

25.5 ppb 

(acute freshwater 

invertebrates, crustaceans)A

2 0 0 0 0 0 

5.2 ppb (non-listed algae) 6 1 2 0 1 0 

A Nonlisted freshwater mollusk, acute COC 9.5 ppb: Number of days were not computed for this taxa group, 

however, expect days of exceedance to be just under the number of days of exceedance as that for nonlisted algae. 

For example, for the High-end, No Treatment (0% removal), about 5 days is a rough estimate based on linear 

interpolation. 
Page 37 of 103

Table 10: Estimates of Numbers of Day Per Year of Exceedance of Endangered/Listed 

COCs for Freshwater Organisms Downstream of Moderate-Size Recirculating Cooling 

Towers (0.0029 kg/site/day release of ATMD before treatment based on 2.5 ppm residual of 

product (42.5 ug/L active ingredient)) 

Endangered/Listed 

COCsA

Number of Days per Year of Exceedance of COCs 

No WWT (0% 

Removal) 

71% Removal During 

WWT 

92% Removal During 

WWT 

High-end Average High-end Average High-end Average 

20 ppb (Listed aquatic 

vascular plants) 2 0 1 0 0 0 

6 ppb (acute listed 

freshwater fish 5 1 2 0 0 0 

2.6 ppb 

(acute listed freshwater 

invertebrates, crustaceans)A

12 1 4 0 1 0 

2.4 ppb (Listed algae) 12 1 4 0 1 0 

A Listed freshwater mollusk, acute COC 0.95 ppb: Number of days were not computed for this taxa group, however, 

expect days of exceedance to be higher than the number of days of exceedance as that for listed algae. 

Table 11: Estimates of Numbers of Day Per Year of Exceedance of Chronic COCs for 

Freshwater Organisms Downstream of Moderate-Size Recirculating Cooling Towers 

(0.0029 kg/site/day release of ATMD before treatment based on 2.5 ppm residual of 

product (42.5 ug/L active ingredient)) 

Chronic COCs 

Number of Days per Year of Exceedance of COCs 

No WWT (0% 

Removal) 

71% Removal During 

WWT 

92% Removal During 

WWT 

High-end Average High-end Average High-end Average 

16 ppb (Freshwater 

Invertebrate) 3 1 1 0 0 0 

4 ppb (Freshwater fish) 8 1 3 0 1 0 

Large-Size Recirculating Cooling Towers

 Tables 12 through 14 present estimates of numbers of days per year of exceedance of 

concentrations of concern (COCs) for freshwater organisms downstream of large-size 

recirculating cooling towers. Table 12 presents estimates of the number of days per year of 

exceedance of acute COCs for freshwater organisms, table 13 presents estimates of the number 

of days per year of exceedance of COCs for endangered/listed freshwater organisms, and table 

14 presents estimates of the number of days per year of exceedance of chronic COCs for 

freshwater fish and invertebrates. 
Page 38 of 103

Table 12: Estimates of Numbers of Day Per Year of Exceedance of Acute COCs for 

Freshwater Organisms Downstream of Large-Size Recirculating Cooling Towers (0.0029 

kg/site/day release of ATMD before treatment based on 2.5 ppm residual of product (42.5 

ug/L active ingredient)) 

Acute COCsA

Number of Days per Year of Exceedance of COCs 

No Treatment (0% 

Removal) 

71% Removal 

During WWT 

92% Removal 

During WWT 

High-end Average High-end Average High-end Average 

123 ppb (Non-listed aquatic 

vascular plants) 12 1 4 0 1 0 

60 ppb (acute freshwater fish 25 3 8 1 3 0 

25.5 ppb 

(acute freshwater 

invertebrates, crustaceans)A

55 6 18 2 5 1 

5.2 ppb (non-listed algae) 155 17 73 7 24 2 

A Nonlisted freshwater mollusk, acute COC 9.5 ppb: Number of days were not computed for this taxa group, 

however, expect days of exceedance to be under the number of days of exceedance as that for nonlisted algae. For 

example, for the High-end, No Treatment (0% removal), about 134 days is a rough estimate based on linear 

interpolation.

Table 13: Estimates of Numbers of Day Per Year of Exceedance of Endangered/Listed 

COCs for Freshwater Organisms Downstream of Large-Size Recirculating Cooling Towers 

(0.0029 kg/site/day release of ATMD before treatment based on 2.5 ppm residual of 

product (42.5 ug/L active ingredient)) 

Endangered/Listed COCsA

Number of Days per Year of Exceedance of COCs 

No WWT (0% 

Removal) 

71% Removal 

During WWT 

92% Removal 

During WWT 

High-end Average High-end Average High-end Average 

20 ppb (Listed aquatic 

vascular plants) 67 7 22 2 7 1 

6 ppb (acute listed 

freshwater fish 144 15 66 7 21 2 

2.6 ppb 

(acute listed freshwater 

invertebrates, crustaceans)A

215 26 116 12 46 5 

2.4 ppb (Listed algae) 220 26 121 13 49 5 

A Listed freshwater mollusk, acute COC 0.95 ppb: Number of days were not computed for this taxa group, however, 

expect days of exceedance to be greater than the number of days of exceedance as that for listed algae. 
Page 39 of 103

Table 14: Estimates of Numbers of Day Per Year of Exceedance of Chronic COCs for 

Freshwater Organisms Downstream of Large-Size Recirculating Cooling Towers (0.0029 

kg/site/day release of ATMD before treatment based on 2.5 ppm residual of product (42.5 

ug/L active ingredient)) 

Chronic COCs 

Number of Days per Year of Exceedance of COCs 

No WWT (0% 

Removal) 

71% Removal 

During WWT 

92% Removal 

During WWT 

High-end Average High-end Average High-end Average 

16 ppb (Freshwater 

Invertebrate) 79 8 28 3 8 1 

4 ppb (Freshwater fish ) 177 20 88 9 31 3 

Once-through cooling systems

 Tables 15 through 18 present estimates of numbers of days per year of exceedance of 

concentrations of concern (COCs) for freshwater organisms downstream of once-through cooling 

systems. Estimates presented for once-through cooling systems are for four different intake flow 

values: 2 MGD, 20 MGD, 50 MGD, and 100 MGD. The estimated number of days per year of 

exceedance of concentrations of concern increase as the intake flow increases 

Table 15: Estimates of Numbers of Days of Exceedance of COCs for Freshwater 

Organisms Downstream of Once-through cooling systems with an Intake Flow of 2 Million 

Gallons per Day (MGD) Assuming No Treatment and 2.5 ppm Residual of Product (42.5 

ug/L active ingredient, ATMD) 

High-end Estimate of Number 

of Days per Year of 

Exceedance of COCs 

Average Case Estimate of 

Number of Days per Year of 

Exceedance of COCs 

Acute COCs 

123 ppb (Non-listed freshwater 

vascular plants) 2 3 

60 ppb (Freshwater fish) 52 5 

25.5 ppb (Freshwater invertebrates, 

crustaceans)A 97 10 

5.2 ppb (algae) 219 26 

Endangered/Listed COCs 

20 ppb (freshwater vascular plants) 112 12 

6 ppb (freshwater fish) 206 24 

2.6 ppb (freshwater invertebrates, 

crustaceans)B 276 38 

2.4 ppb (algae) 280 39 

Chronic COCs 

16 ppb (Freshwater Invertebrate) 127 13 
Page 40 of 103

High-end Estimate of Number 

of Days per Year of 

Exceedance of COCs 

Average Case Estimate of 

Number of Days per Year of 

Exceedance of COCs 

4 ppb (Freshwater Fish) 240 30 A Nonlisted freshwater mollusk, acute COC 9.5 ppb: Number of days were not computed for this taxa group, 

however, expect days of exceedance to be just under the number of days of exceedance as that for nonlisted algae. 

Based on linear interpolation estimates of number of days of exceedance are 193 and 22 days, for the High-end and 

average case, respectively. 

B Listed freshwater mollusk, acute COC 0.95 ppb: Number of days were not computed for this taxa group, however, 

expect days of exceedance to be greater than the number of days of exceedance as that for listed algae. 

Table 16: Estimates of Numbers of Days of Exceedance of COCs for Freshwater 

Organisms Downstream of Once-through cooling systems with an Intake Flow of 20 

Million Gallons per Day (MGD) Assuming No Treatment and 2.5 ppm Residual of Product 

(42.5 ug/L active ingredient, ATMD) 

High-end Estimate of 

Number of Days per Year of 

Exceedance of COCs 

Average Case Estimate of 

Number of Days per Year of 

Exceedance of COCs 

Acute COCs 

123 ppb (Non-listed freshwater 

vascular plants) 148 16 

60 ppb (Freshwater fish) 207 24 

25.5 ppb (Freshwater invertebrates, 

crustaceans)A 276 38 

5.2 ppb (algae) 348 81 

Endangered/Listed COCs 

20 ppb (freshwater vascular plants) 293 43 

6 ppb (freshwater fish) 345 76 

2.6 ppb (freshwater invertebrates, 

crustaceans)B 357 111 

2.4 ppb (algae) 357 114 

Chronic COCs 

16 ppb (Freshwater Invertebrate) 307 48 

4 ppb (Freshwater Fish) 352 91 A Nonlisted freshwater mollusk, acute COC 9.5 ppb: Number of days were not computed for this taxa group, 

however, expect days of exceedance to be just under the number of days of exceedance as that for nonlisted algae. 

Based on linear interpolation estimates of number of days of exceedance are 333 and 72 days, for the High-end and 

average case, respectively. 

B Listed freshwater mollusk, acute COC 0.95 ppb: Number of days were not computed for this taxa group, however, 

expect days of exceedance to be greater than the number of days of exceedance as that for listed algae. 
Page 41 of 103

Table 17: Estimates of Numbers of Days of Exceedance of COCs for Freshwater 

Organisms Downstream of Once-through cooling systems with an Intake Flow of 50 

Million Gallons per Day (MGD) Assuming No Treatment and 2.5 ppm Residual of Product 

(42.5 ug/L active ingredient, ATMD) 

High-end Estimate of 

Number of Days per Year of 

Exceedance of COCs 

Average Case Estimate of 

Number of Days per Year of 

Exceedance of COCs 

Acute COCs 

123 ppb (Non-listed freshwater 

vascular plants) 224 27 

60 ppb (Freshwater fish) 281 40 

25.5 ppb (Freshwater invertebrates, 

crustaceans)A 329 59 

5.2 ppb (algae) 358 122 

Endangered/Listed COCs 

20 ppb (freshwater vascular plants) 338 66 

6 ppb (freshwater fish) 357 114 

2.6 ppb (freshwater invertebrates, 

crustaceans)B 360 161 

2.4 ppb (algae) 360 165 

Chronic COCs 

16 ppb (Freshwater Invertebrate) 344 73 

4 ppb (Freshwater Fish) 359 136 A Nonlisted freshwater mollusk, acute COC 9.5 ppb: Number of days were not computed for this taxa group, 

however, expect days of exceedance to be just under the number of days of exceedance as that for nonlisted algae. 

Based on linear interpolation estimates of number of days of exceedance are 352 and 109 days, for the High-end and 

average case, respectively. 

B Listed freshwater mollusk, acute COC 0.95 ppb: Number of days were not computed for this taxa group, however, 

expect days of exceedance to be greater than the number of days of exceedance as that for listed algae.

Table 18: Estimates of Numbers of Days of Exceedance of COCs for Freshwater 

Organisms Downstream of Once-through cooling systems with an Intake Flow of 100 

Million Gallons per Day (MGD) Assuming No Treatment and 2.5 ppm Residual of Product 

(42.5 ug/L active ingredient, ATMD) 

High-end Estimate of 

Number of Days per Year of 

Exceedance of COCs 

Average Case Estimate of 

Number of Days per Year of 

Exceedance of COCs 

Acute COCs 

123 ppb (Non-listed freshwater 

vascular plants) 279 39 

60 ppb (Freshwater fish) 322 55 

25.5 ppb (Freshwater invertebrates, 

crustaceans)A 349 82 

5.2 ppb (algae) 360 160 

Endangered/Listed COCs 

20 ppb (freshwater vascular plants) 352 91 
Page 42 of 103

High-end Estimate of 

Number of Days per Year of 

Exceedance of COCs 

Average Case Estimate of 

Number of Days per Year of 

Exceedance of COCs 

6 ppb (freshwater fish) 359 152 

2.6 ppb (freshwater invertebrates, 

crustaceans)B 360 200 

2.4 ppb (algae) 360 204 

Chronic COCs 

16 ppb (Freshwater Invertebrate) 355 101 

4 ppb (Freshwater Fish) 360 175 A Nonlisted freshwater mollusk, acute COC 9.5 ppb: Number of days were not computed for this taxa group, 

however, expect days of exceedance to be just under the number of days of exceedance as that for nonlisted algae. 

Based on linear interpolation estimates of number of days of exceedance are 358 and 143 days, for the High-end and 

average case, respectively. 

B Listed freshwater mollusk, acute COC 0.95 ppb: Number of days were not computed for this taxa group, however, 

expect days of exceedance to be greater than the number of days of exceedance as that for listed algae. 

4.3.2 Estimation of Risks to Freshwater Benthic Invertebrates Exposed to ATMD in

Sediments

 Acute and chronic RQs and presumption of risk based on comparison to LOC values are 

discussed in Appendix D. Based on the freshwater high-end exposure scenario (10th percentile 

7Q10 distribution and associated concentrations of ATMD in sediments estimated from data on 

potential leaching adsorption-desorption of ATMD to soil, RQs for listed and nonlisted benthic 

organisms exceed the LOC for subchronic risk for once-through and large-size recirculating 

cooling towers with no treatment (Table 19). Based on average exposure (50th percentile), the 

LOC is not exceeded for any cooling tower scenario. However, because there is no freshwater 

amphipod toxicity endpoint currently available, additional exceedances might occur for both 

exposure scenarios if the amphipod is a more sensitive species than the midge. The approach 

used to estimate sediment concentrations presented in Table 19 is discussed in Appendix E. 

Table 19: Risk Quotients for Freshwater Benthic Organisms Based on Estimated 

Concentrations of ATMD in Sediment (sediment concentrations for 10th and 50th 

percentile 7Q10 Distribution) 

Cooling System Scenario 

10th percentile 50th percentile 

Sediment 

Concentration 

(mg ai/kgsediment) 

RQ1 

Sediment 

Concentration 

(mg ai/kgsediment) 

RQ1 

Freshwater: 

Once-Through Cooling System 

(2 MGD) with No Treatment 1053.8 5.6* 10.54 0.06 
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Cooling System Scenario 

10th percentile 50th percentile 

Sediment 

Concentration 

(mg ai/kgsediment) 

RQ1 

Sediment 

Concentration 

(mg ai/kgsediment) 

RQ1 

Large-Size Recirculating 

Cooling Tower (144 MGD) with 

No Treatment484 2.6* 4.76 0.02 

Large-Size Recirculating 

Cooling Tower with 71 Percent 

Removal During Wastewater 

Treatment 

143.2 0.76 1.44 <0.01 

Large-Size Recirculating 

Cooling Tower with 92 Percent 

Removal During Wastewater 

Treatment 

39.5 0.21 0.41 <0.01 

Moderate-Size Recirculating 

Cooling Tower (2.88 MGD) with 

No Treatment 

9.52 0.05 .095 <0.01 

Moderate-Size Recirculating 

Cooling Tower with 71 Percent 

Removal During Wastewater 

Treatment 

2.77 0.01 .028 <0.01 

Moderate-Size Recirculating 

Cooling Tower with 92 Percent 

Removal During Wastewater 

Treatment 

0.78 <0.01 .0078 <0.01 

1

 RQ = sediment concentration/toxicity, where freshwater midge EC50 = 188 mg ai/kg sediment 

* exceeds the LOC for risk to benthic organisms 

4.3.3 Estimation of Risks to Estuarine/Marine Organisms Exposed to ATMD in the

Water Column

 Acute RQs comparing the concentration of ATMD at the discharge source (i.e., end of 

pipe concentration of 42.5 ug/L ATMD) to the available toxicity endpoints exceed the acute 

LOCs for listed fish, listed and non-listed invertebrates, and non-listed algae (Table 20). The 

most acutely sensitive estuarine invertebrates are mollusks as represented by tests with the 

Quahog clam (Mercenaria mercenaria), with an EC50 = 19 μg ai/L. Acute testing with another 

invertebrate, a crustacean—the mysid shrimp, Mysidopsis bahia (LC50 = 61 μg ai/L)—was also 

available but was not as sensitive as mollusks. One acute toxicity value is available for estuarine 

fish, the Atlantic silverside (Menidia menidia; LC50 = 155 μg ai/L), and toxicity data also are 

available for Skeletonema costatum (EC50 = 11 μg ai/L), a marine diatom. Chronic NOAECs 

for fish and invertebrates were extrapolated from ACRs (see Table 7). 
Page 44 of 103

 The concentrations of concern for listed and nonlisted species can then be calculated for 

each receptor group to determine the dilution factors that are needed to minimize these risks. 

Dilution factors of 4 to 5.5X would be sufficient to minimize risks to aquatic plants, listed fish, 

and nonlisted aquatic invertebrates. A dilution factor of 45X would be needed to minimize 

potential risks to listed estuarine mollusk invertebrates whereas a factor of 2 is sufficient for 

crustaceans. 

Table 20: Concentrations of Concern for Risk to Water Column-Dwelling 

Estuarine/Marine Organisms and Dilution Factors That Would Minimize Risks 

Receptor group RQ Federal status Concentration of 

concern (μg ai/L) 

Dilution factor 

needed to minimize 

risk 

Acute: 

 Fish 0.27* Listed spp. 7.8 5.5 

Nonlisted spp. 77.5 0 

 Invertebrates – 

Mollusks 2.23** Listed spp. 0.95 45 

Nonlisted spp. 9.5 4.5 

Chronic: 

 Fish 8.3*** Listed and 

Nonlisted spp. 

5.1 8-8.5 

 Invertebrates 2.2*** 19 2-3 

Plants:

 Algae 3.8# Nonlisted1 11 4 

Vascular plants 0.3 Nonlisted spp. 123 0 

2## Listed spp. 42.5 2 

* Exceeds the acute LOC for listed species (acute RQ >0.05) 

**Exceeds the acute LOCs for listed (acute RQ >0.05) and nonlisted (acute RQ >0.5) species 

***Exceeds the chronic LOC (chronic RQ>1) #

Exceeds the LOC for non-listed aquatic plants (non-listed RQ >1) ## Exceeds the LOC for listed aquatic plants (listed RQ >1) 1

 no algal species are currently listed 

4.3.4 Estimation of Risks to Estuarine/Marine Benthic Invertebrates Exposed to

ATMD in Sediments

 The risk quotient for estuarine benthic organisms is determined by comparing the worst 

case sediment exposure estimate (1445.7 mg ai /kg sediment) to the available toxicity data for 

the estuarine/marine amphipod (10-day EC50 = 303 mg ai/kg sediment). The RQ = 4.77, which 

exceeds the LOC for risk to estuarine benthic organisms. 
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4.3.5 Estimation of Risks to Piscivorous Birds and Mammals  

 Piscivorous birds (e.g., herons, gulls, osprey) and mammals (e.g., otter, mink) are likely 

to feed on fish and invertebrates that have been exposed to ATMD in the water column. ATMD 

has some potential to bioconcentrate in fish (BCF = 378-388X, whole fish). An upper bound 

exposure based on an end-of-pipe discharge concentration of 42.5 μg ai/L (0.0425 mg ai/L) or 

less would result in low tissue levels, and the extent of bioconcentration will be mitigated by the 

strong tendency of ATMD to bind to suspended sediments. For birds, the greatest mitigating 

factor is that ATMD is only slightly toxic to practically nontoxic when administered in their diet 

(LC50s >5000 ppm, 8 studies). Other mitigating factors such as proportion of population 

exposed on the day of release, proportion of diet these organisms would constitute, growth 

dilution, sediment burial, etc. all make it unlikely to result in any detectable residues of concern. 

While there are no acute or reproduction data for mammals, to assess human health hazards a 90-

d NOAEL of 0.4 mg/kg-bw/day value from an oral gavage study using laboratory rats was 

selected in lieu of acute and chronic data. Like with birds, at the upper bound end-of-pipe 

concentration effects to mammals are not considered likely given all the mitigating factors. 

4.4 Ecological Risk Characterization

 To characterize the potential exposures and risks from this proposed new use of ATMD, 

it is important to consider limitations and uncertainties for the following key aspects of this risk 

assessment: 

 EPA’s modeling of ecological exposures and risks; 

 Uncertainties resulting from ecotoxicity data gaps; 

 Uncertainties resulting from environmental fate data gaps; 

 Mexel’s modeling of ecological exposures and risks; and 

 Whole Effluent toxicity testing submitted by Mexel. 

Evaluation of EPA’s Ecological Exposure and Risk Assessment Modeling Results

 When interpreting the results of EPA’s human and ecological risk assessment, it is 

important to note that sorption of ATMD to suspended solids in the water column was not 

quantitatively considered. By extrapolation from laboratory studies on adsorption/desorption of 

ATMD in soils, ATMD would be expected to have a very high potential to sorb to suspended 

sediments in the water column. Since EPA’s E-FAST model was unable to account for the 

phenomenon of sorption of ATMD to suspended sediments in the water column, this would lead 
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to overestimates of surface water concentrations predicted downstream of facilities where 

ATMD would be expected to be used. 

 EPA ecological modeling results are based on loadings that would estimate surface water 

concentrations for peak exposures. EPA’s models require input in units of kilograms ATMD per 

site per day to estimate surface water concentrations downstream of facilities that use ATMD. 

According to use instructions on the label, the daily dose of MEXEL 432/0 is 4.0 ppm for 30 

minutes with a residual concentration of 2.5 ppm. (The residual concentration of ATMD at 1.7% 

in product would be 42.4 ug/L.) The label also states that normal frequency of treatment is once 

per day or as needed to maintain control. Since the label contained no upper limit on the 

frequency of treatment on a daily basis, loadings of ATMD in kg/site/day EPA used in modeling 

assumed that a 2.5 ppm residual product (42.5 ug/L ATMD) would be maintained continuously 

over a 24-hour period. This assumption serves two purposes: (1) It provides estimates of peak 

exposures that are needed to estimates acute risks to aquatic organisms and (2) it provides a 

worst case exposure estimate based on the lack of an upper limit of application frequency on the 

product label. 

 If the maximum application of MEXEL 432/0 is limited to a single dose applied daily for 

30 minutes, peak daily hourly and chronic peak risk estimates used to assess exposures to aquatic 

organisms would be reduced. Based on guidelines for Whole Effluent Toxicity tests, for acute 

criteria, EPA recommends an averaging period of 1 hour and for chronic criteria an averaging 

period of 4 days. Based on these guidelines, daily loadings that EPA used in its modeling for 

calculating acute exposures would decrease by a factor of 2 and for chronic exposures by a factor 

of 48.

 EPA’s E-FAST modeling results are based on the ratio of distributions of plant flows to 

stream flows for facilities in the Standard Industrial Classification (SIC) code for Steam Electric 

Power Plants (4911). There are instances in which stream flow and/or plant flow data may be 

missing for a facility. In instances in which the plant effluent flow is greater than the stream 

flow, E-FAST assumes that the effluent flow is equal to the stream flow; in cases where the 

stream flow is greater than the plant effluent flow, the stream flow is equal to the sum of the 

stream flow and plant effluent flow. Consequently, it is possible that unrealistic plant flow to 

stream flow ratios can occur that would depict conditions that would not be likely to be found 

under real-world conditions; this would be expected to introduce uncertainties that would 

generally tend to lead to overestimates of exposures and risks. 

 Due to the somewhat static nature of estuarine/marine water bodies relative to flowing 

freshwater bodies, potential exposure and risks to aquatic organisms in estuarine/marine water 

bodies may be higher than those to aquatic organisms in freshwater bodies. Suspended solids 

content of estuarine/marine systems, however, might generally be expected to be higher than that 

for freshwater systems leading to greater potential for sorption of ATMD, which could reduce 
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potential exposures to organisms in the water column, but increase exposures to sedimentdwelling organisms. 

Uncertainties Resulting from Gaps in Ecotoxicity Data

There are several uncertainties associated with gaps in the ecotoxicity profile. For freshwater 

benthic organisms, data are available only for the midge. Lack of data for an amphipod might 

results in risk being underestimated if the amphipod is more sensitive than the midge. In the 

absence of data for fish and estuarine/marine invertebrates, Acute-Chronic Ratios (ACRs) were 

used to extrapolate NOAECs. Some uncertainty exists in extrapolating from freshwater species 

to estuarine/marine species, because the chronic mode of action may differ. An Interspecies 

Correlation Estimation (ICE) model also was used to extrapolate an LC50 for the fathead 

minnow and an EC50 for cyanobacteria. Additionally, all available acute and chronic 

ecotoxicity data are based on continuous exposure (e. g., 96-h fish LC50, 21-day invertebrate life 

cycle). However, if MEXEL 432/0 is applied for a maximum of only 30 minutes per day, 

exposure would be intermittent rather than continuous. Although the Agency has not reviewed 

the data, summary toxicity endpoint values presented for freshwater fish and daphnids in a 

mixing zone evaluation for a nuclear plant indicate that intermittent exposure of 20 minutes per 

day results in lower toxicity to aquatic organisms than do the endpoints from continuous 

exposure. If toxicity is less from intermittent exposure, then the LOC exceedances might be 

reduced over those calculated for MEXEL 432/0. Lastly, ecotoxicity data are not available for 

the product, which is only 1.7% ai. Any toxicity due to the inert ingredients would be in addition 

to that of the TGAI and might result in an underestimation of acute and chronic toxicity to 

aquatic organisms. 

Uncertainties Resulting from Gaps in Environmental Fate Data

 The registrant has not submitted guideline aquatic metabolism studies for ATMD. These 

studies would provide information on the formation and decline of potential degradates. Aerobic 

aquatic metabolism data (835.4300) represent the water column in a water body while anaerobic 

aquatic metabolism data (835.4400) represent benthic and suspended sediments. In lieu of 

aquatic metabolism guideline studies, the registrant provided literature studies to address the 

persistence of alkyl amines and degradates in sediment and water. The literature studies7

demonstrated that degradation of alkylamines occurs, but none of these studies provided 

estimates of half-life of alkylamines or their metabolic intermediates in the aquatic environment, 

 

7

 Cerniglia and Perry (1975), Nguyen et al. (2008), and van Ginkel et al. (2008) 
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and therefore their persistence of ATMD in the aquatic environment cannot be estimated at this 

time (MRIDs 49208802, 49208803). As a result, the Agency assumed stability of ATMD in the 

aquatic environment since no aerobic and anaerobic aquatic metabolism studies were submitted 

that would provide information on the potential rate of formation and decline of degradates. 

Data on aerobic and anaerobic aquatic metabolism of ATMD would allow the Agency to develop 

a more refined estimate of potential exposures and risks to ecological organisms. 

Evaluation of Modeling Results Provided by Mexel  

 In a non-guideline study submitted to the Agency (Ackerman, D, F Ghillebaert, and MW 

Glass, 2013: MRID 49040220), Mexel used two modeling approaches to estimate exposures and 

risks to aquatic organisms downstream of two power plants. The first modeling approach used 

the site-specific option of the General Population and Ecological Exposure from Industrial 

Releases module of E-FAST to provide screening level estimates of exposures to aquatic 

organisms. The second approach used the higher tier CE-QUAL-W2 model to provide more 

refined estimates of exposures to aquatic organisms. This higher tier model demonstrated 

reduction in concentrations of ATMD with distance downstream of the facilities modeled and 

considered influences of stream bathymetry characteristics on surface water concentrations. 

Mexel considered the two power plants they selected for modeling to be atypical and to have the 

greatest impact. One power plant, the Hammond Power Plant near Rome, Georgia was selected 

to be representative of the distribution of facilities in Standard Industrial Classification Code 

(SIC) 4911 (i.e., steam electric power plants); Mexel reports that this power plant was in the 95th

percentile of all power plant discharges and that its discharge flow of 2082 million liters per day 

(MLD) was approximately equal to the 7Q10 flow of the Coosa River downstream of the plant 

(i.e., 2927 MLD), representing a realistic case where the dilutive capacity of the receiving water 

would be at a minimum. The second power plant, the Crockett Power Plant near Girvin, TX was 

selected by Mexel to investigate the impacts of using ATMD at a smaller power plant on a 

smaller stream, the Pecos River; Mexel reports that the discharge flow from this power plant, 

5.29 MLD was in the 37th percentile of the distribution of power plants and that the 7Q10 flow of 

the Pecos river downstream of the plant is 5.24 MLD (mean stream flow is 1674 MLD). 

 In estimating loadings used as inputs for modeling, Mexel assumed that the product, 

MEXEL 432/0, would be applied over a 30-minute period to achieve a maintenance 

concentration of ATMD of 42.5 ug/L. Mexel estimated that this concentration would result in 

1.04 kg/day of ATMD being released to surface water from the Hammond Power Plant and 

0.00468 kg/day of ATMD being released to surface water from the Crockett Power Plant. These 

daily loading estimates that Mexel used as inputs to the Industrial Releases module of E-FAST 

were derived by averaging a single loading of 30 minutes duration over a 24-hour period; these 

loadings were further reduced to reflect a 44 percent “immediate demand” that was 
Page 49 of 103

representative of the range of “immediate demands” from 21 to 86% for the formulated end use 

product (EP). This “immediate demand” is applied to account for removal as a result of 

adsorption of ATMD to suspended sediments in the water column. Averaging the amount of 

ATMD applied during a 30-minute period over a 24-hour period and further reducing loadings 

by applying a factor for “immediate demand” tend to underestimate potential acute exposure to 

aquatic organisms, but might be appropriate for estimating potential chronic risks to aquatic 

organisms. 

 According to the proposed product label, “Normal frequency of treatment is once per day 

or as needed to maintain control. The amount of the daily dose is determined by the circuit 

characteristics. The daily dose is 4.0 ppm for 30 minutes with a residual concentration of 2.5 

ppm.” As noted earlier, the maintenance concentration of 2.5 ppm corresponds to 42.5 ug/L 

ATMD. Since the label does not specify an upper limit on the number of applications of product 

per day and specifies maintenance of a residual concentration of 2.5 ppm product, EPA estimates 

that as a worst case up to 88.5 kg/day of ATMD could be released to surface water from the 

Hammond Power Plant as compared to Mexel’s assumption of 1.04 kg/day. 

 In selecting facilities as candidates for modeling using E-FAST, Mexel eliminated from 

further consideration 878 of 1277 power plants in the E-FAST database of facilities in SIC 4911 

(Steam Electric Power Plants). Power plants eliminated included those reported to have no 

discharge and those with 7Q10 flows reported to be 0 MLD. In addition, Mexel also eliminated 

streams that had low flows (7Q10) less than the plant discharge flows, leaving 399 facilities as 

candidates for site-specific modeling. 

 Although Mexel provided information on where the two facilities they modeled lie along 

the distribution of plant flows for the 399 of 1277 facilities selected as potential candidates for 

modeling, it is not clear where these facilities would lie with regard to potential exposure and 

risk for all 1277 facilities within SIC code 4911. Results on days per year of exceedance for the 

two facilities modeled are general (presented in graphs) with no results provided for specific 

COCs. 

 Although the two facilities modeled by Mexel might provide conservative estimates of 

exposure relative to other facilities where ATMD could be used, EPA cannot conclude based on 

modeling results provided by the registrant from 2 of 1277 facilities in the Steam Electric Power 

Plants SIC code that that the use of ATMD at these types of facilities will not pose potential 

concerns for exposure and risk to aquatic organisms for all facilities on flowing water bodies 

where the proposed new use of this chemical may occur. , Additionally, these modeling results 

would not be representative of facilities located on estuarine/marine water bodies. 
Page 50 of 103

Evaluation of WET Results Submitted by Mexel

 Whole effluent toxicity testing from two facilities, Calvert Cliffs Nuclear Power Plant 

(CCNPP) and Donald C. Cook Nuclear Power Plant (DCCNPP) conducting efficacy trials with 

Mexel were submitted by the registrant (MRID 49208816); details of these studies are provided 

in Appendix E. CCNPP is located along an estuarine area of the Potomac River and DCCNPP is 

located along the shore of Lake Michigan. Both facilities have once through cooling systems. 

The design flow is 3460 million gallons per day at CCNPP and 2405 million gallons per day at 

CCNPP. The studies show that under certain dosing regimes and mixing zones there are 

facilities that would be able to use Mexel in once through cooling systems without resulting in 

unreasonable adverse effects to the aquatic environment. For facilities that need to meet limits at 

the end-of-pipe, however, the proposed label rate would result in exceedances for once-through 

systems. 

 Chronic short-term whole effluent toxicity testing was conducted at CCNPP with both an 

estuarine fish and shrimp species. The 7-day NOAECs were 50%, 100% and 100% for Inland 

silverside and 100% and 100% for mysids. While the studies as presented in the drafts appear to 

be scientifically sound studies for the specific facility and its treatment regime, critical primary 

study design information was missing from the package provided which would allow the study 

results to bridge to use in other cooling water systems, and the highest allowed label application 

regime. Specifically, unknown timing between dosing of cooling water system and collection of 

effluent, the lack of dosing the cooling water system with Mexel on all effluent collection days 

which is assumed to mean no ATMD would be present in effluent, and the lack of dosing 

information for some dates (e.g., all of June, July) during the effluent collection period. 

Additionally, no analytical measurements were made on ATMD levels present in the 100% 

effluent. While such analytical information was not necessary for the purpose of the study, to 

bridge to other water cooling systems such information is critical. 

 Acute whole effluent testing with a freshwater fish and cladoceran were conducted at 

DCCNPP. Three types of effluent samples were tested for each species: 

 A 24-h composite effluent sample where grab samples occurred hourly and where Mexel 

was applied for 30 minutes during one of these hours; 

 An effluent grab sample from the 30 minute Mexel dosing period in the previous bullet; 

and 

Lake water dosed with Mexel from a pilot test rig mixed with two gallons of untreated lake water 

to simulate a 3:1 dilution. 

 The 24-h composite 48-h LC50 for D. magna and the 96-h LC50 for the fathead minnow 

were both greater than the concentration found in 100% effluent. The single grab sample had a 

fathead minnow 96-hour LC50 of 27.7% effluent and the D. magna a 48-h LC50 of 35.4% 

effluent. Based on these results a mixing zone with a dilution of 3:1 was postulated as being able 
Page 51 of 103

to meet a Tier I acute ambient water quality criterion of 0.1 ppm Mexel, developed for the 

facility. However, the one 3:1 dilution test from the pilot test rig study still showed acute 

mortality occurring (LC50 = 66% effluent for both species). 

4.7 Section 4 References

Ackerman, D, F Ghillebaert, and MW Glass. 2013. Duomeen C Water Concentration Modeling 

for Cooling Towers and Once-Through Industrial Cooling Water Systems. Non-guideline study. 

MRID 49040220. 

EPA. 2013. Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: 

User Manual (version 3.2). EPA/600/R-12/603. USEPA Office of Research and Development, 

Gulf Ecology Division, Gulf Breeze, FL http://www.epa.gov/ceampubl/fchain/webice/

EPA. 2010. Predicting the Toxicities of Chemicals to Aquatic Animal Species. USEPA Office 

of Water and Office of Pesticide Programs, Washington, DC; Office of Research and 

Development, Gulf Ecology Division; and Office of Research and Development, Mid-Continent 

Ecology Division. October 27, 2010. 

 
Page 52 of 103

5.0 SUMMARY OF POTENTIAL HUMAN AND ECOLOGICAL RISKS

 This document presents the United States Environmental Protection Agency’s human and 

ecological risk assessment for the new use of the active ingredient, N-coco 1,3-diaminopropane 

(also sometimes referred to as N-(coco alkyl)trimethylenendiamine, Duomeen C, and ATMD) in 

MEXEL 432/0 to control biofouling in once-through and recirculating cooling towers. The 

active ingredient in MEXEL 432/0 is generally hereinafter referred to as ATMD 

(alkyltrimethylenediamine). 

 MEXEL 432/0 is to be used for the control of biofouling, including zebra mussels and 

clams in once-through cooling and cooling tower circuits with closed delivery systems for nonpotable industrial freshwater and sea water systems. The product may be applied to maintain 

clean systems or to treat systems that are already fouled. Normal frequency of treatment is once 

per day or as needed to maintain control. The amount of the daily dose is determined by the 

circuit characteristics. The daily dose is 4.0 ppm for 30 minutes with a residual concentration of 

2.5 ppm. 

 According to the product label, the concentration of active ingredient, ATMD, is 1.7 

percent. Based on maintenance of 2.5 ppm product residual, this corresponds to 42.5 ug/L 

ATMD. 

 ATMD would not be expected to be more toxic than alternative chemical substances that 

could be used as cooling tower biofoulants. Since facilities that would be expected to use 

ATMD have NPDES permits, there would be no increased regulatory burden. 

 The exposure scenarios that form the basis of EPA’s risk assessment include releases to 

surface water from: 

 large-size recirculating cooling towers; 

 moderate-size recirculating cooling towers; and 

 once-through cooling systems. 

For recirculating cooling towers, exposures from releases of ATMD to surface water were 

estimated with and without wastewater treatment. For once-through cooling systems, it was 

assumed that no treatment of effluent occurs prior to discharge to surface water. 

 This risk assessment considers risks to both humans and ecological organisms. Risks to 

humans evaluated in this assessment include potential dietary risks from ingestion of drinking 

water and potential risks from occupational exposure during mixing and loading of ATMD. 

Estimates of potential dietary risks to humans from ingestion of drinking water were determined 

to be negligible based on worst case estimates of drinking water concentrations and published 

information on drinking water consumption by humans at a high level of consumption. 
Page 53 of 103

Although potential risks were identified for occupational dermal and inhalation exposure during 

mixing and loading, these risks can be minimized if the label specifies that the proposed product 

be applied using closed loading and delivery systems. (The label currently only specifies “closed 

delivery systems”.) 

 The ecological risk assessment for ATMD considers three key components: 

 EPA’s assessment of risks to ecological organisms from exposure to ATMD; 

 Whole Effluent Toxicity (WET) test data on submitted by the registrant; and 

 Site-Specific modeling submitted by the registrant. 

 When interpreting the results of EPA’s human and ecological risk assessment, it is 

important to note that sorption of ATMD to suspended solids in the water column was not 

quantitatively considered. By extrapolation from laboratory studies on adsorption/desorption of 

ATMD in soils, ATMD would be expected to have a very high potential to sorb to suspended 

sediments in the water column. Since EPA’s E-FAST model was unable to account for the 

phenomenon of sorption of ATMD to suspended sediments in the water column, this would lead 

to overestimates of surface water concentrations predicted downstream of facilities where 

ATMD would be expected to be used. 

 EPA ecological modeling results are based on loadings that would estimate surface water 

concentrations for peak exposures. Two general quantitative approaches were used by EPA to 

assess risks to ecological organisms: a risk quotient (RQ) method and a probabilistic method 

(These are discussed further in Appendix E). The probabilistic approach was used to estimate 

potential risks to freshwater fish and invertebrates. Both average case and high end scenarios 

were evaluated. For the high-end scenario, results of the number of days per year that COCs are 

exceeded is based on the upper 10th percentile of the ratio of stream flows to plant flows (Also 

referred to as Stream Dilution Factors (SDFs) . For the average case scenario, results of the 

number of days per year that COCs are exceeded are based on the 50th percentile of SDFs. For 

the upper 10th percentile SDFs, or high-end scenario, the stream flow to plant flow ratio is 

relatively low since plant flows can contribute considerable volume to the flow of the stream and 

resulting surface water concentrations can be relatively high. For the 50th%ile SDF, the stream 

flow to plant flow ratio is more typical. 

 The risk quotient method was used to estimate potential risks to freshwater benthic 

invertebrates, marine/estuarine freshwater fish and invertebrates, and estuarine/marine benthic 

organisms. In addition, for marine/estuarine fish and invertebrates, dilution factors that would be 

needed to mitigate exceedance of concentrations of concern were estimated. In estimating 

sediment concentrations of ATMD to which freshwater benthic organisms would be exposed, 

estimated surface water concentrations were multiplied by an average experimentally-determined 

adsorption/desorption value. In estimating sediment concentrations to which estuarine/marine 

organisms would be exposed, the effluent concentration of ATMD at the end of pipe from 
Page 54 of 103

information on the product label was multiplied by an average experimentally-determined 

adsorption/desorption value. A qualitative approach was used to estimate potential risks to 

piscivorus birds and mammals. 

 Releases of ATMD from recirculating cooling towers to receiving water bodies and 

associated exposures are predicted to be much lower than those from once-through cooling 

systems. First, releases from recirculating cooling towers are from blowdown water, which 

constitutes a fraction of the total cooling tower intake flow, whereas releases from once-through 

cooling systems consist of the total intake flow. (Blowdown is assumed to be only 0.06 percent 

of recirculating cooling tower intake flow.) Second, effluents from recirculating cooling towers 

may possibly undergo wastewater treatment whereas effluents from once-through cooling 

systems would not. . 

 Tables 9, 10 and 11 present estimates of numbers of days per year of exceedance of 

concentrations of concern (COCs) for freshwater organisms downstream of moderate-size 

recirculating cooling towers based on releases of ATMD with and without wastewater treatment. 

Tables 12, 13, and 14 present estimates of numbers of days per year of exceedance of COCs for 

freshwater organisms downstream of large-size recirculating cooling towers based on releases of 

ATMD with and without wastewater treatment. Tables 15 through 18 present estimates of 

numbers of days per year of exceedance of COCs for freshwater organisms downstream of oncethrough cooling systems at intake flow values of 2, 20, 50, and 100 million gallons per day 

(MGD), respectively. Exceedance of an acute COC and of an endangered/listed COC for one 

day or more indicates that there may be potential acute adverse effects to freshwater organisms. 

Exceedance of chronic COCs for 20 days or more indicates that there may be potential chronic 

adverse effects to freshwater organisms. 

 If the maximum application of MEXEL 432/0 is limited to a single dose applied daily for 

30 minutes, peak daily hourly and chronic peak risk estimates used to assess exposures to aquatic 

organisms would be reduced. Based on guidelines for Whole Effluent Toxicity tests, for acute 

criteria, EPA recommends an averaging period of 1 hour and for chronic criteria an averaging 

period of 4 days. Based on these guidelines, loadings that EPA used in its modeling for 

calculating acute exposures would decrease by a factor of 2 and for chronic exposures by a factor 

of 48. 

 EPA used the risk quotient method to estimate potential risks to freshwater benthic 

organisms. These results are presented in Table 19. Based on sediment concentrations derived 

from the high-end scenario (10th percentile of stream flow to plant flow distribution), the level of 

concern would be exceeded for large size recirculating cooling towers with no treatment and for 

once-through cooling systems. Based on the average case scenario, there would be no 

exceedances of levels of concern for freshwater benthic organisms. 
Page 55 of 103

 EPA used the risk quotient method and end of pipe concentrations of ATMD to 

determine worst case estimates of risks to estuarine/marine fish and invertebrates exposed to 

ATMD in the water column and to estuarine/marine benthic invertebrates in sediments. Table 20 

presents dilution factors that would be needed to reduce risks to below concentrations of concern 

for water-column dwelling estuarine/marine organisms. Based on a worst case estimate of the 

concentration of ATMD in estuarine/marine sediment, the level of concern for estuarine/marine 

benthic organisms would be exceeded. 

 Based on a qualitative evaluation, EPA determined that potential risks to piscivorus birds 

and mammals would be negligible. 

 In a non-guideline study submitted to the Agency (Ackerman, D, F Ghillebaert, and 

M.W. Glass, 2013: MRID 49040220), Mexel used two modeling approaches to estimate 

exposures and risks to aquatic organisms downstream of two power plants. The first modeling 

approach used the site-specific option of the General Population and Ecological Exposure from 

Industrial Releases module of E-FAST (i.e., Industrial Releases module) to provide screening 

level estimates of exposures to aquatic organisms. The second approach used the higher tier CEQUAL-W2 model to provide more refined estimates of exposures to aquatic organisms.. 

 The daily loading estimates that Mexel used as inputs to the Industrial Releases module 

of E-FAST were derived by averaging a single loading of 30 minutes duration over a 24-hour 

period. These loadings were further reduced to reflect a 44 percent “immediate demand” that 

was representative of the range of “immediate demands” from 21 to 86% for the formulated end 

use product (EP). This “immediate demand” is applied to account for removal as a result of 

adsorption of ATMD to suspended sediments in the water column. Averaging the amount of 

ATMD applied during a 30-minute period over a 24-hour period and further reducing loadings 

by applying a factor for “immediate demand” tend to underestimate potential acute exposure to 

aquatic organisms, but might be appropriate for estimating potential chronic risks to aquatic 

organisms. Results on days per year of exceedance for the two facilities modeled are general 

(presented in graphs) with no results provided for specific COCs. 

 Although the two facilities modeled by Mexel might provide conservative estimates of 

exposure relative to other facilities where ATMD could be used, EPA cannot conclude based on 

these modeling results that the use of ATMD at these types of facilities will not pose potential 

concerns for exposure and risk to aquatic organisms for all facilities where the proposed new use 

of this chemical may occur. Additionally, these modeling results are not representative of 

facilities located on estuarine/marine water bodies. 

 Whole effluent toxicity testing from two facilities, Calvert Cliffs Nuclear Power Plant 

(CCNPP) and Donald C. Cook Nuclear Power Plant (DCCNPP) conducting efficacy trials with 

Mexel were submitted by the registrant (MRID 49208816); details of these studies are provided 

in Appendix E. Both facilities have once through cooling systems. The studies show that under 
Page 56 of 103

certain dosing regimes and mixing zones there are facilities that would be able to use Mexel in 

once through cooling systems without resulting in unreasonable adverse effects to the aquatic 

environment. For facilities that need to meet limits at the end-of-pipe, however, the proposed 

label rate would result in exceedances for once-through systems. 

 There are uncertainties associated with gaps in ecotoxicity data including lack of data on 

a second species of benthic invertebrates, estimates from WEB-ICE and acute to chronic ratio 

estimates. Some summary information appeared to indicate that intermittent exposures would 

result in lower toxicity than continuous exposures, but the Agency did not have enough 

information to review. Also, ecotoxicity data were only available for the active ingredient and 

no data were available on the formulated product; data for the TGAI, which comprises 1.7% of 

the product, may underestimate the toxicity of the formulation. 

 Further, there are uncertainties associated with gaps in environmental fate data. The 

Agency assumed stability of ATMD in the aquatic environment since no aerobic and anaerobic 

aquatic metabolism studies were submitted that would provide information on the potential rate 

of formation and decline of degradates. Data on aerobic and anaerobic aquatic metabolism of 

ATMD would allow the Agency to develop a more refined estimate of potential exposures and 

risks to ecological organisms. 

 Finally, although ATMD would be expected to have a very high potential to sorb to 

suspended sediments in the water column, EPA’s models were unable to account for this 

phenomenon. Therefore, estimated surface water concentrations do not quantitatively consider 

this removal process. 

 In summary, there are no potential risks for human health from the use of ATMD as a 

biofoulant in cooling towers if the proposed label is modified to require “closed loading and 

delivery systems”. There are also no risks of concern for piscivorus birds from the cooling tower 

use. 

 There are potential risks of concern to all aquatic organisms both freshwater and 

estuarine organisms from the use of ATMD as a biofoulant. These risks are expected to be 

similar to risks from other antimicrobial pesticides which are used as antifoulants. Risks are 

higher for once through towers than for recirculating towers and higher for large facilities than 

for small or moderate size facilities. Estimated acute and chronic risks to aquatic organisms in 

the water column would be lower and potentially eliminated in some instances if the proposed 

label is modified to limit application to a maximum of one 30-minute application per day and if 

the potential for sorption to suspended sediments is accounted for. 

 
Page 57 of 103

APPENDIX A: ENVIRONMENTAL FATE DATA

Introduction

 ATMD is a mixed alkyl triethylene diamine surfactant (surface acting agent) with alkyl 

chains that contain 8-18 carbons in even increments. The predominant constituents (C12, C14, 

C16, and C18) accounted for 45.3, 16.2, 9.5, and 11.1 % of the total mixture, respectively. Taken 

together, the four predominant constituents account for 82.1 % of the parent mixture. The 

remaining diamine compounds (C8 and C10) account for a total of 9.3 % of the parent mixture 

(MRID 49040203). 

 The registrant submitted product chemistry studies for their product which contain 

information that appears to be useful for risk assessment. The UV Visible absorption spectrum 

study indicates that the maximum sorption is in the range of 202-218 nanometers (nm) of 

wavelength, with only a small amount of absorption in the 290-350 nm range (MRID 49040202). 

As a result of this limited UV sorption, minimal photodegradation by sunlight is expected. The 

weighted average8

 octanol-water partitioning coefficient (log P) of the N-coco-1,3-

diaminopropane product was 0.2 (unitless), but it ranged from -3 (for C8 alkyl chain) to 2-2.5 

(for C18 alkyl chain) [MRID 49040203]. Based on this log P value, this mixed product can 

bioconcentrate but is not expected to have high bioconcentration in aquatic organisms.9,

10 The 

water solubility for the entire product is relatively low because of the alkyl carbon chain, and is 

approximately 10 mg/l (ppm) (MRIDs 49040204, 48486702). 

 ATMD is used in non-potable water systems (once-through and recirculating) and some 

residues will reach the environment from this use. Once ATMD reaches the environment, the 

extent of dissipation by different routes will vary. Chemical degradation of ATMD (hydrolysis 

and photodegradation) is not expected to be significant route of dissipation11. The extent of 

microbial degradation in the aquatic environment is uncertain because the registrant did not 

address the persistence of parent alkylamines (or suitable surrogates) in sediment and water and 

did not provide information on the persistence of the reduced-length chain degradates of alkyl 

amines12) If the effluent from the treated water systems is released directly to surface water and 

not treated, it will reach surface water where it will sorb strongly to bottom and suspended 

sediment (~99 %) in as little as two hours. The Kf (whole soil) sorption values were 14,454-

 

8

 Weighted arithmetic mean of (log P for each compound * percentage in mixture)/91.4 % diamine content. 9

 TG OECD 305 states that a compound having a log P of >3 does not have “high” lipophilicity 10 http://www.epa.gov/scipoly/sap/meetings/2008/october/305_bioconcentration_flowthrough_fish_test.pdf 11 MRIDs 40062413, 41069001, and 93034010 for hydrolysis and 49040202 and 49208801for photodegradation in 

water 

12 MRIDs 49208802, 49208803, 
Page 58 of 103

50,898 ml/g and Koc (sorption values onto organic carbon were 696,677-4,551,033 ml/g with 1/n 

values of 0.48-0.8213. Some bioconcentration in fish will occur, based on bioconcentration 

factors (BCFs) of 82-180X (edible), 525-610X (non-edible), and 378-388X (whole fish). The 50 

% depuration times were 17 days (edible), 8.5-21 days (non-edible), and 9.2-30 days (whole 

fish).14 Bioconcentration in fish will be more likely in streams with limited amounts of 

suspended sediment to sorb any active ingredient that may reach water. However, in streams 

with a significant amount of suspended sediment, the extent of bioconcentration will be limited 

by the sorption to sediment (>99 %) by 2 hours15 and in sludge (~83 %) by 4-6 hours.16 

 In a WWTP, the primary route of dissipation is expected to be sorption to activated 

sludge with some biodegradation. ATMD was strongly sorbed to activated sludge with Kf 

values of 39,753 and Koc values of 105,222 L/kg by 24 hours. The extent of sorption increased 

with time based on 71-92 % sorption by 4-6 hours (mean of 83 %) and 94-98 % sorption by 12-

24 hours (mean of 96 %) (MRID 49040205). ATMD was not readily biodegradable in an 

OECD 301D Closed Bottle test (MRID 49040207). At 2 mg/l of ATMD, the registrant reported 

that 69 % of the theoretical oxygen demand (ThOD) was reached by 28 days, and therefore 

ATMD should be considered to be readily biodegradable. However, this result does not meet the 

pass criterion established for this guideline. The OECD 301D test guideline criterion for ready 

biodegradability in a Closed Bottle test is 60 % of ThOD in a 14-day period, and this 14-day 

period starts when 10 % of ThOD disappears and must end by before day 28 of the test.17 In the 

study, 10 % ThOD disappearance occurred at approximately 8 days, and the maximum percent 

ThOD disappearance in any 14-day window was 42 % (from 8-18 days). In the ASRI study 

there were inadequate sampling concentrations between 10 and 30 mg/l of test substance where 

nearly 80 % inhibition occurred with no concentration intervals in-between. The calculated IC50

was 22 mg/l with a 95 % confidence interval of 10-30 mg/l.18 A biodegradation simulation test, 

such as OCSPP 835.3240, 835.3280, or 835.3220, would be more appropriate as a measure of 

biodegradability during activated sludge treatment than the ready biodegradability test (OCSPP 

835.3110). 

 

13 MRID 49040206 

14 MRID 49040210 

15 MRID 49040206 

16 MRID 49040205 

17 P. 3, OECD 301, http://www.oecd.org/chemicalsafety/risk-assessment/1948209.pdf 18 MRID 49040218 
Page 59 of 103

Product Chemistry  

 The registrant submitted product chemistry studies for N-coco-1,3-diaminopropane 

which considered in this risk assessment to contain usable information.19 These studies included 

the UV visible absorption spectrum (OCSPP 830.7050)20, octanol-water partition coefficient 

(Log P or Log Kow, OCSPP 830.7550)21, and water solubility (OCSPP 830.7840)22. 

 The UV Visible absorption spectrum study indicates that the maximum sorption is in the 

range of 202-218 nm of wavelength, but a small amount of absorption does occur from 290-350 

nm (MRID 49040202). However, the small amount of absorption above 290 nm was not 

deemed to be significant to create potential photodegradation in water (OCSPP 835.2240)23 as a 

route of dissipation in the environment.24 

 The Log P or Log Kow study (OCSPP 830.7550) study results are used to indicate the 

potential or lack of potential for bioconcentration in fish (OCSPP 850.1730)25 and activated 

sludge sorption isotherm (OCSPP 835.1110).26 The weighted average log P value of the Ncoco-1,3-diaminopropane product in MRID 49040203 was 0.2 (unitless). However, the log P 

ranged from -3 (for C8 alkyl chain) to 2-2.5 (for C18 alkyl chain). Based on this log P value, this 

mixed product can bioconcentrate but is not expected to have high bioconcentration in aquatic 

organisms.27,

28 The registrant submitted separate studies for bioconcentration in fish and 

activated sludge sorption isotherm which are summarized below.29 

 The water solubility study (OCSPP 830.7840) results are variable for N-coco-1,3-

diaminopropane. Because N-coco-1,3-diaminopropane contains C8-C18 alkyl chains, the 

chemical and physical properties will vary with the chain length. According to the registrant, 

83.4 % of the formulation has high solubility (>10 mg/l), 14.9 % has low solubility (<10 mg/l), 

and 1.7 % is insoluble. In addition, the formulated product has dispersants and adjuvants which 

 

19 MRIDs 49040202, 49040203, 49040204 

20 OCSPP 830.7050, UV/Visible Absorption, http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT2009-0151-0024 21 OCSPP 830.7550, Partition Coefficient (n-Octanol/Water), Shake Flask Method, 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0151-0031 22OCSPP 830.7840, Water Solubility: Column Elution Method; Shake Flask Method, 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0151-0034 23 OCSPP 835.2240, Photodegradation in water, EPA-HQ-OPPT-2009-0152-0012[1].pdf , 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0012 24 Jennings, August 19, 2013. D411969 

25 OCSPP 850.1730, Fish BCF, 

http://www.epa.gov/ocspp/pubs/frs/publications/OPPTS_Harmonized/850_Ecological_Effects_Test_Guidelines/Dra

fts/850-1730.pdf 26 OCSPP 835.1110, Activated sludge sorption isotherm, http://www.regulations.gov/#!documentDetail;D=EPAHQ-OPPT-2009-0152-0003 . 27 TG OECD 305 states that a compound having a log P of >3 does not have “high” lipophilicity 28 http://www.epa.gov/scipoly/sap/meetings/2008/october/305_bioconcentration_flowthrough_fish_test.pdf 29 Bioconcentration in fish (MRID 49040206) and Activated sludge sorption isotherm (MRID 49040205) 
Page 60 of 103

increase the water solubility and product efficacy. As a result, the solubility of the end-use 

product Mexel 432/O is “high” (>10 mg/l) [MRID 49040204]. However, the solubility in 

another guideline study is given as “<10.5 mg/l” (MRID 48486702).30 

Fate in a Cooling Tower 

 The method of action of the Mexel 432/0 product is different from most conventional 

treatments. The product is not focused on delivering a lethal dose or trying to remove fouling 

that has built up over time due to ineffective on-going control. Used on a cleaned system, the 

Mexel 432/0 is intended to prevent fouling by creating a microscopic layer of a filming amine 

that largely controls fouling from progressing. This film prevents biofilms from gaining a 

foothold that can lead to corrosion, deposits, and poor heat transfer. This also helps prevent the 

build-up of layers of fouling that are hard to penetrate and allow some microbes become resistant 

to conventional treatments. When these problems are prevented, the amount of chemicals 

introduced to the environment for routine treatment and remedial chemical treatment and other 

special maintenance (e.g. acid tube cleaning) is substantially reduced (MRID 49040221). 

Environmental Fate

Hydrolysis  

 The alkyl trimethylenediamines compound, 1-(alkyl* amino)-3-aminopropane diacetate 

(applied as Duomeen-C Diacetate, 51.9% a.i. in isopropanol), has been shown to be 

hydrolytically stable under abiotic and buffered conditions over the pH 5-9 range and under 

abiotic and unbuffered conditions in deionized water over a 30-day incubation period (MRIDs 

40062413, 41069001, and 93034010). 

Photodegradation in Water

 Photodegradation in water is not expected to be a significant route of dissipation for Ncoco-1,3-diaminopropane. The UV Visible absorption spectrum study indicates that the 

maximum sorption is in the range of 202-218 nm of wavelength, but a small amount of 

absorption does occur from 290-350 nm (MRID 49040202). The photodegradation in water 

study requires light that is filtered to remove wavelengths below 290 nm, and the study will not 

provide any useful information on the dissipation of N-coco-1,3-diaminopropane in the 

environment. 

 

30 Sinning, May 16, 2011 
Page 61 of 103

Aerobic Aquatic Metabolism  

 The registrant has submitted numerous articles on the degradation of surfactants, and 

these articles (1) did not address the persistence of parent alkylamines (or suitable surrogate) in 

sediment and water and (2) did not provide information on the persistence of the reduced-length 

chain degradates of alkyl amines. 

Anaerobic Aquatic Metabolism

 The registrant has submitted numerous literature studies on the metabolism of various 

surfactants (Curcio and Ghillebaert, 2013). Some of these studies related to specific 

microorganisms that can use diamine molecules as a sole carbon source. The significance of 

these studies for the degradation of Duomeen C is unclear because, in general, the degradation of 

alkylamines is dependent upon a consortium of microorganisms (Nguyen et al. 2008) and a 

particular bacterium may or may not be ubiquitous in wastewater treatment. These studies 

included Cerniglia and Perry (1975), Nguyen et al. (2008), and van Ginkel et al. (2008). 

Cerniglia and Perry (1975) studied the degradation of monoamine and diamine molecules by the 

aerobic bacterium Mycobacterium convolutum. It is not clear if this study is useful because the 

degradation of propylamines may not be representative of Duomeen C, which contains a 

diethylene amine functional group. This study does not specifically address any long-chain 

carbons such as the ones in the Duomeen C molecule. Nguyen et al (2008) studied the effect of 

anaerobic conditions and the presence of a denitrifying bacterium Pseudomonas stutzeri on the 

degradation of long-chain alkyl amines, including cocoamine (C8-C18 aliphatic saturated chain), 

oleylamine (C18 amine chain containing double bond), and tallowamine (C18 amine chain 

containing double bond). For all of these compounds, degradation occurred by deamination 

followed by beta-oxidation of the C8-C18 alkyl chains. Van Ginkel et al. (2008) studied the effect 

of the bacterium Pseudomonas sp. BERT on the degradation of amines containing C3-C18 alkyl 

chains. In all cases, degradation occurred by deamination followed by beta-oxidation of the 

alkyl chains, with successive formation of alkanal groups (alkane chain with aldehyde functional 

group) and fatty acids (carboxylic acids) that degrade to CO2, water, and bacterial biomass. 

However, none of the literature citations provided any estimates of half-life of these metabolic 

intermediates. 

Leaching­Adsorption­Desorption

 ATMD was tightly sorbed onto five soils with Kf (whole soil) sorption values of 14,454-

50,898 ml/g (mean of 34,016 L/kg) and sorption values onto organic carbon (Koc) of 696,677-

4,551,033 L/kg (mean of 1,926,433 L/kg). Nearly all (>99 %) of Duomeen C was sorbed in the 

study (MRID 49040206). Sorption was related to cation exchange capacity (CEC) with r2 of 
Page 62 of 103

0.55 which indicates that sorption is a function of clay content (r2

=0.16), organic carbon content 

(r2=0.21), and pH (r2=0.33)31. 

 Because sorption to soil was not primarily a function of organic carbon content, the 

Agency used the mean Kf value of 34,016 L/kg to calculate Koc sorption in sediment that may 

receive ATMD residues from cooling towers. This approach was based on the “Guidance for 

Selecting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides” 

from the Environmental Fate and Effects Division of OPP.32 The input parameters for the 

EXAMS model, which represents surface water, were followed for ATMD because sorption was 

not primarily related to soil organic carbon content. The mean Kf of 34,016 L/kg was divided 

by each sediment organic carbon content listed in Table 20 below (0.002, 0.01, 0.02, 0.04, and 

0.05 % as decimal) and each derived Koc was used in the General Population and Ecological 

Exposure from Industrial Releases module of E-FAST. 

Bioconcentration in Fish

 The bioconcentration in fish study includes experiments on bioconcentration of parent ncoco-1,3-diaminopropane in bluegill sunfish (Lepomis macrochirus). For the edible, non-edible, 

and whole fish, the steady-state bioconcentration factors were 180X, 525X, and 378X for the 

0.85 ug/l rate and 82X, 610X, and 388X for the 7.2 ug/l rate, respectively. For the 0.85 ug/l 

treatment, the 50 % depuration time ranged from 21-30 days for the non-edible and whole fish 

tissue. However, it was not possible to determine the depuration time for the edible tissue 

because the concentrations were close to the LOQ. For the 7.2 ug/l treatment, the 50 % 

depuration times were 17, 8.5, and 9.2 days for the edible, non-edible, and whole fish, 

respectively. 

Sorption to Activated Sludge

 Duomeen C was tightly sorbed to activated sludge. By 4-6 hours, 71-92 % sorption of 

Duomeen C was observed (mean of 83 %). By 12-24 hours, 94-98 % sorption (mean of 96 %) 

was observed. The calculated Kf and Koc values for a 24-hour sorption test were 39,753 and Koc 

of 105,222 ml/g, respectively (MRID 49040205). 

The above sorption interval times and % sorption values in MRID 49040205 were based on the 

preliminary portion of the study to determine the appropriate equilibrium time used in the final 

portion of the sorption to activated sludge study. According to the FAO33, the Hydraulic 

Retention Time in the aeration tanks usually ranges from 3-8 hours but can be higher with high 

 

31 Linear regression run on hydrogen ion concentrations and not logarithmic pH value 

32 http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm 33 http://www.fao.org/docrep/t0551e/t0551e05.htm
Page 63 of 103

BOD wastewaters. According to Boethling34, a “reasonable” retention time for full-scale 

systems is 6-8 hours. As a result, the sorption the sorption data from 4-6 hours are appropriate 

for environmental modeling. 

Activated Sludge Respiration Inhibition (ASRI)

 According to the ASRI study (MRID 49040218), the IC50 value for ATMD was 22 mg/l 

with a 95 % confidence interval of 10-30 mg/l. The percent respiration inhibition ranged from -

1.5 % at 10 mg/l to 77.8 % at 30 mg/l with no concentration intervals between. As a result, it 

cannot be concluded with reasonable confidence that the activated sludge IC50 is greater than 20 

mg/L, which is the OPP threshold used to determine the type of WWTP biodegradation testing to 

perform to indicate the percent removal via biodegradation by activated sludge 

microorganisms.35 

Biodegradability in Wastewater Treatment  

ATMD is not expected to degrade rapidly in wastewater because it was not determined to be 

readily biodegradable in an OECD 301D Closed Bottle test (MRID 49040207) . At 2 mg/l of 

ATMD, the registrant reported that 69 % of the theoretical oxygen demand (ThOD) was reached 

by 28 days, and therefore ATMD should be considered to be readily biodegradable. However, 

this result does not meet the pass criterion established for this guideline. The OECD 301D test 

guideline criterion for ready biodegradability in a Closed Bottle test is 60 % of ThOD in a 14-

day period, and this 14-day period starts when 10 % of ThOD disappears and must end by before 

day 28 of the test.36 In the study, 10 % ThOD disappearance occurred at approximately 8 days, 

and the maximum percent ThOD disappearance in any 14-day window was 42 % (from 8-22 

days). 

 

34 November 22, 2013 e-mail from Bob Boethling of EPA to Pat Jennings of EPA 

35 November 22, 2013 e-mail from Bob Boethling of EPA to Pat Jennings of EPA 

36 P. 3, OECD 301, http://www.oecd.org/chemicalsafety/risk-assessment/1948209.pdf 
Page 64 of 103

Table 21. Chemical, Physical, and Environmental Fate Properties of Duomeen C from EPI-Suite 4.11 and 

N-coco-1,3-diaminopropane homolog 

Guideline Guidelin

e (OCSPP number unless specified) 

Unit C8 C10 C12 C14 C16 C18 

Percentage of each homolog in Duomeen C 

830.1550 % 4 5.3 45.3 16.2 9.5 

Molecular formula None None C11H26N2 C13H30N2 C15H34N2 C17H38N2 C19H42N2 CSmiles code None None 

CCCCCCCCNCCCN 

CCCCCCCCCCNCCCN 

CCCCCCCCCCCCNCCCN 

CCCCCCCCCCCCCCNCCCN 

CCCCCCCCCCCCCCCCNCCCN 

CCCCCCCCN

Molecular weight None g/mol 186.34 214.40 242.45 270.51 298.56 Relative density 830.7300 g/cm3 0.84 

0.96 

Melting point 830.7200 oC Not available (product is a mixture of crystals, solids, and viscous liquid at room temperature) Boiling point 830.7220 oC 302 Water solubility 830.7840 mg/l 

High solubility (>10 mg/l) of diamine surfactant complex based on presence of adjuvants and dispersa

<10.5 mg/l (maximum concentration of diamine surfactant complex in water) 

Vapor Pressure (mm Hg) 

830.7950 mm Hg 6 (formulated product including liquid phase) 

Henry’s Law None 

atm m3

mol-1

Not calculated because of uncertain vapor pressure and water solubility. 
Page 65 of 103

N-coco-1,3-diaminopropane homolog 

Guideline Guidelin

e (OCSPP number unless specified) 

Unit C8 C10 C12 C14 C16 C18 

Log P (log Kow) 830.7550 Unitl ess -3 -1.9 -0.8 0.4 1.6 Hydrolysis 835.2120 Days Stable at pH 5, 7, and 9 Photodegradation in water 835.2240 Days Assumed to be essentially stable to photodegradation because of limited sorption of UV light by active ingKoc values to be used for EFAST model 

835.1230 L/kg 

For modeling, use Koc derived from mean Kf of 34,016 L/Kg based on policy guidance for the E

model stating that if sorption is not related to organic carbon, use the mean Kf.37

EXAMS model simulates aquatic environment. The Koc values below were calculated by divisio

Kf by the Sediment OC values listed below. 

Sediment OC values for EFAST Modeling (decimal) Derived Koc Values based on Mean Kf (

0.002 1.7 x 107

0.01 3.4 x 1060.02 1.7 x 1060.04 8.5 x 1050.05 6 x 105

Leachingadsorptiondesorption to soil 

835.1230 ml/g 

Kf of 14,454-50,898 L/kg, Koc of 696,677-4,551,033 L/kg 

1/n ranged from 0.48 to 0.82 (<1) 

Straight arithmetic mean of 34,016 L/kg for Kf and 1,926,433 L/kg for Koc 

>99 % sorption for all 5 soils starting at the 2-hour equilibrium time (24 hours used in final t

Sorption related to cation exchange capacity (CEC) with r2 of 0.55 which indicates that sorptio

function of clay content (r2=0.16), organic carbon content (r2=0.21), and pH (r2=0.33)38

Texture pH Clay 

(%) 

 OC 

(%) 

CEC 

(meq/100g) 

Kf (L/kg) 

(from 

study) 

Koc (L/kg) 

(from 

study) 

1/n 

st

37 http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm38 Linear regression in Excel with (x) values of run on Hydrogen ion concentration and not pH 
Page 66 of 103

N-coco-1,3-diaminopropane homolog 

Guideline Guidelin

e (OCSPP number unless specified) 

Unit C8 C10 C12 C14 C16 C18 

Silt loam 7.1 25 4.2 24.1 50,898 1,211,857 

Sandy loam 6.1 17 2 17.2 38,362 1,968,100 

Clay loam 5.3 29 4.3 22 29,957 696,677 

Loamy sand 5.6 11 1.2 11.7 14,454 1,204,500 

Clay 7.7 44 1.8 25.4 36,408 4,551,033 

Aerobic aquatic metabolism 

835.4300 Days Persistence of parent alkylamines (or suitable surrogate) in sediment and water and information 

persistence of the reduced-length chain degradates of alkyl amines not provided. 

Anaerobic aquatic metabolism 

835.4400 Days 

Degradation occurred by deamination followed by beta-oxidation of the alkyl chains, with succ

formation of alkanal groups (alkane chain with aldehyde functional group) and fatty acids (carb

acids) that degrade to CO2, water, and bacterial biomass. However, none of the literature cita

provided any estimates of half-life of the metabolic intermediates. 

Activated sludge sorption 

835.1110 %, L/kg 71-92 % sorption by 4-6 hours (mean of 83 % sorption) 94-98 % sorption by 12-24 hours (mean of 96 % sorption) Kf of 39,753, Koc of 105,222 L/kg 

Ready biodegradability 

835.3110 

OECD 

301D 

% Readily biodegradable (69 % biodegraded by 28 days in Closed Bottle test)

Activated sludge respiration inhibition 

850.3300 mg/l EC50 value was 21.9 mg/L.

Bioconcentration in fish39 850.1730 Unitl ess 

Edible, non-edible, and whole fish 

BCF of 180X, 525X, and 378X for the 0.85 ug/l rate 

BCF of 82X, 610X, and 388X for 7.2 ug/l rate 

50 % depuration occurred at 21and 30 days for non-edible and whole fish at 0.85 ug/l 

50 % depuration occurred at 17, 8, and 9 for edible, non-edible and whole fish at 7.2 ug/l 

39 BCF predictions should increase as the water solubility decreases and log Kow increases. 
Page 67 of 103

APPENDIX A REFERENCES

Bisinger, Jr., E.C. Hydrolysis Study: Environmental Fate Data Requirements. Unpublished 

study performed and submitted by Akzo Chemie America, Chicago Il. MRID 40062413 

Bisinger, Jr., E. C. April 14, 1989. Hydrolysis of Duomeen-C Acetate: Environmental Fate Data 

Requirements. Unpublished study performed and submitted by Akzo Chemicals, Chicago, IL. 

MRID 41069001 

Cerniglia, C.E., and Perry, J.J., 1975. Metabolism of n-propylamine, isopropylamine, and 1,3-

propane diamine by Mycobacterium convolutum. J. Bacteriol., 124(1): 285-289. 

Curcio, L.N. and F. Ghillebaert. September 4, 2013. Response to data requirements 

deficiencies: OCSPP 835.4400-Anaerobic aquatic metabolism. Unpublished study sponsored 

and submitted by Mexel USA, LLC, Arlington, VA. MRID 49208803. 

Curcio, L.; Ghillebaert, F. (2013) Response to Data Requirements Deficiencies: Aerobic Aquatic 

Metabolism. Project Number: MEXEL/432/0. Unpublished study prepared by Ecotox and The 

Solutous Group. 131p. MRID 49208802 

Curcio, L.; Ghillebaert, F. (2013) Environmental, Ecological and Health Effects (Tier 1) for 

Duomeen C, the TGAI in the EP Mexel 432/0. Unpublished study prepared by Mexel USA, 

LLC. 702p. MRID 49040219 

Curcio, L.; Ghillebaert, F. (2013) Requested Supplemental Data for Waiver Passing Technical 

Screen: Photodegradation in Water. Project Number: MEXEL/432/0. Unpublished study 

prepared by Ecotox and The Solutous Group. 34p. MRID 49208801 

Ellison, F. (1993) Duomeen C: Physical and Chemical Characteristics of Duomeen C: Physical 

State, Boiling Point, Specific Gravity, Solubility, Vapor Pressure, pH, Stability, Oxidizing or 

Reducing, Explodability and Viscosity: Final Report: Lab Project Number: 00459-002. 

Unpublished study prepared by Case Consulting Labs, Inc. 19 p. MRID 43029202 

Farnback, M. July 16, 2012. Determination of the Partition Coefficient (1-octanol/water) for 

Duomeen C. OCSPP Guideline 830.7550. Unpublished study performed by Casco Adhesives 

AB, Sweden, and submitted by Mexel Industries, France. MRID 49040203 

Kendall, T.Z and W.B. Nixon. March 13, 2013. Analytical Method Verification of Duomeen C 

in Freshwater Wildlife International Ltd. Project No. 709C-101. Unpublished study performed 

by Wildlife International, Easton, MD, and submitted by Mexel Industries, Arlington, VA. 

MRID 49040201 

Murrell, J.R. and W. B. Nixon. April 5, 2012. Determination of the Ultraviolet-Visible 

Absorption Spectrum of Duomeen C. Wildlife International Project No. 709C-103. 

Unpublished study conducted by Wildlife International, Easton, MD, and submitted by Mexel 

Industries, Arlington, VA. MRID 49040202 

Nguyen, P.O., van Ginkel, C.G. and Plugge, C.M., 2008. Anaerobic degradation of long-chain 

alkylamines by a denitrifying Pseudomonas stutzeri. FEMS Microbial. Ecol. , 66(1) :136-142 
Page 68 of 103

Rausch, L. (1990) Akzo Chemicals, Inc. Phase 3 Summary of MRID 41069001. Hydrolysis of 

Duomeen-C Diacetate. Prepared by AKZO CHEMICALS INC. 10 p. MRID 93034010 

Schaefer, E.; Ponizovsky, A. (2012) Duomeen C: Activated Sludge Sorption Isotherm. Project 

Number: 709E/103/OCR. Unpublished study prepared by Wildlife International, Ltd. 65p. 

MRID 49040205 

Schaefer, E.C. and Twilley, B.C., 2011 . Duomeen C: An activated sludge, respiration inhibition 

test. Project ID 709E-1 01 , performed on behalf of Mexel Industries, SAS. MRID 49040218 

Schaefer, E.C. and Ponizovsky, A.A., 2012b. Duomeen C: Adsorption/Desorption 

Characteristics In Five Representative Soils. Project ID 709E-102, Wildlife International, Ltd., 

Performed on behalf of Mexel Industries, SAS. 124 pp. MRID 49040206 

Sinning, D. December 2, 2010. Physical and Chemical Characteristics of Mexel 432/0: Color, 

Physical State, Odor, Oxidation/Reduction: Chemical Incompatibility, Flammability, pH, 

Viscosity, and Relative Density. Project Number: 4800/01. Unpublished study prepared by Case 

Consulting Laboratories, Inc. 9 p. MRID 42022502 

Sinning, D. . May 16, 2011. Physical and Chemical Characteristics of Duomeen C: Color, 

Physical State, Odor, Stability, pH, UV/Vis, Boiling Point, Density, Dissociation Constant, 

Octanol/Water Partition Coefficient and Solubility: Final Report. Project Number: 4870/02. 

Unpublished study prepared by Case Consulting Laboratories, Inc. 32 p. MRID 48486702 

Thomas, S.T., Kendall, T.Z., and Gallagher, S.P., 2013. Duomeen C: A flow-through 

bioconcentration test with the bluegill (Lepomis macrochirus). Project ID 709A-110, Wildlife 

International, Ltd., Performed on behalf of Mexel Industries, SAS. 115 pp. MRID 49040210 

US EPA, 2012b. Estimation Programs Interface SuiteTM for Microsoft® Windows, v 4.11. 

United States Environmental Protection Agency, Washington, DC, USA 

http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm 

van Ginkel, C. G., Louwerse, A., and van der Togt, B., 2008b. Substrate specificity of a long 

chain alkylamine-degrading Pseudomonas sp isolated from activated sludge. Biodegradation 19( 

1): 129-136 

van Ginkel, C.G. May 23, 2012. Biodegradability of n-coco-1,3-diamino-diamineopropane 

(CAS 61791-63-7) in the closed bottle test (OECD TG 301 D). Unpublished study by Akzo 

Nobel Arnhem, study number: T12018C. MRID 49040207 

Velea, Luminita. February 26, 2013. Water Solubility for Mexel 432/P, EPA Reg. No. 84034-1. 

Unpublished study performed by Technology Sciences Group, Washington, DC, and submitted 

by Mexel Industries, Arlington, VA. MRID 49040204 
Page 69 of 103

APPENDIX B: HUMAN HEALTH TOXICITY DATA

Subchronic Toxicity

 An acceptable 90-day oral toxicity study (MRID 49092801) was submitted and 

reviewed. In this study, N -(coco alkyl) trimethylenediamine (94% a.i., Batch No.: S000904) 

was administered to 10 Wistar RjHan:WI rats/sex/dose via oral gavage as a suspension at dose 

levels of 0 (C), 0.1, 0.4, 1.5, or 6 mg/kg/day for 7 days/week for a period of 90 days at a 

volume of 4 ml/kg. There were two recovery groups consisting of 5 animals per sex: one was 

observed for 28 days and one for 90 days following the last compound administration. 

Test item related clinical signs were observed in 1.5 and 6.0 mg/kg/day groups and recovery 

groups. Signs included slight to severe salivation, half-eyelid closure, vocalization, temporary 

stertorous respiration, oral and nasal discharge, dyspnea, weight loss and piloerection. 

Three mortalities in the main groups, (two female from 6.0 and one male from 1.5 mg/kg/day 

groups) and 2 mortalities in high dose females of the 90-day recovery group were observed. 

Dosing error might have been the cause in three of the animals. No cause of death could be 

established in the remaining two females treated at 6 mg/kg/day. 

During the treatment period (days 1 to 90 in the main study and recovery high dose group male 

animals), there was a statistically significant decrease in overall body weight gain [33%] and 

food consumption [16%] compared to the corresponding controls. No change was seen in the 

females. 

No test item related effect occurred in hematology and urine parameters and clinical 

biochemistry parameters in male and females of any group except decreases in total protein in 

the 1.5 and 6.0 mg/kg/day females when compared to the control. 

No effect on organ weight in male and female animals of treated group and recovery group was 

observed which could be considered as a treatment related effect except a decrease in absolute 

liver weights in 6.0 mg/kg/day males, increase in relative kidney weights in 28-day recovery 

males, increase in relative adrenal weights in 6.0 mg/kg/day male and females, and increase in 

relative epididymides weight in 6.0 mg/kg/day males. No histopathology changes were noted 

that could account for the these changes. 

At the terminal sacrifice of the main study and recovery animals, macroscopic findings observed 

were considered to be spontaneous and not treatment related 

Histopathologically, test item-related changes were seen in the small intestine (ileum and 

jejunum), mesenteric lymph node, spleen, bone marrow (sternum) and trachea at 1.5 mg/kg/day 

and above. After the 28-day recovery period, treatment- related changes in the jejunum, ileum 

and mesenteric lymph node were still present in animals of this dose group. Changes noted in the 
Page 70 of 103

spleen had partially regressed and bone marrow (sternum) and tracheal changes had fully 

regressed. After 90 days of recovery, test article-related changes in the jejunum, ileum and 

mesenteric lymph node had partially regressed. No test article-related changes were noted in the 

spleen, bone marrow (sternum) and trachea. 

The NOAEL is 0.4 mg/kg/day. The LOAEL is 1.5 mg/kg/day based on a decrease in body 

weight gain and food consumption in males and histopathology changes in the 

gastrointestinal tract in males and females. 

Developmental Toxicity

A developmental toxicity study was not conducted for N-(coco alkyl)trimethylenediamine [also 

referred to as N-coco 1,3-diaminopropane]. Instead, the registrant cited a study summary that 

was presented in the 2008 European Union Risk Assessment Report for tallow alkyl amines. 

This study was conducted on octadecenylamine, whose structure is shown below: 

The summary of this study is presented below: 

“In the main study, groups of 28 pregnant females were treated orally (gavage) with dosages of 

10, 40 or 80 mg/kg bw/day or with the vehicle (Mazola corn oil) during gestation days 6 to 15. 

During the study animals were examined daily. Any clinical signs of toxicity including physical 

or behavioral abnormalities were recorded. Individual body weights and food consumption were 

recorded on gestation days 0, 6, 9, 12, 16, and 20. Two animals in each group were selected to be 

sacrificed and necropsied after treatment on gestation day 15 to determine the appearance and 

severity of gastrointestinal tract irritation. On gestation day 20 caesarean section was performed 

on all surviving animals. The numbers of viable fetuses, early and late resorptions as well as the 

number of corpora lutea were recorded. Fetuses were examined for external, visceral and skeletal 

abnormalities.” 

“All animals survived to scheduled sacrifice. Outward clinical signs of toxicity were observed at 

the 40 and 80 mg/kg bw/d dose levels. The observations most likely indicated a generalized 

irritative effect of the test substance as characterized by rales, salivation, unkempt appearance 

and changes in the amount, color and consistency of the feces. However, no other signs of 

treatment-related gastrointestinal irritation or other internal changes were observed at the 

gestation day 15 and 20 necropsies. More pronounced signs of toxicity were apparent only in the 

80 mg/kg bw/d dose group and included emaciation, rough coat and dark red material around the 

eyes, nose and/or mouth. Similar clinical signs were infrequently noted during the post-dose 
Page 71 of 103

observations. Dose-dependent body weight loss (during gestation days 6-9) or reduced weight 

gain (during gestation days 12-16), along with a corresponding reduction in food consumption 

occurred during the treatment period in the 40 and 80 mg/kg bw/d dose groups. Net body weight 

gain (adjusted for gravid uterine weight) was also lower at these levels. Following cessation of 

treatment (days 16-20), increase in weight gain and food consumption were noted at both dose 

levels. No such effects were observed in the dose group treated with 10 mg/kg bw/d. Caesarean 

section data obtained from the treated groups did not reveal any meaningful differences 

(concerning number of corpora lutea, implantation sites, viable fetuses, fetal sex and fetal 

weight) when compared with the controls. Fetal evaluations of type and frequency of 

malformations and variations did not reveal any indications for a treatment related teratogenic 

effect. In summary, oral administration of octadecenylamine to pregnant rats produced dosedependent maternal toxicity in the 40 and 80 mg/kg bw/d dose groups. No indications of an 

embryotoxic, fetotoxic or teratogenic effect were observed at any tested level.” 

\ 

“A NOAEL/maternal toxicity of 10 mg/kg bw/d and a NOAEL/developmental 

toxicity of > 80 mg/kg bw/d can be derived from the study.” 

Reproduction and fertility effects

No data on reproduction and fertility effects was submitted for the active ingredient N-(coco 

alkyl)trimethylenediamine [also referred to as N-coco 1,3-diaminopropane]. Instead, the 

registrant cited a summary of a study conducted on tallow alkyl amines. This study was 

conducted according to OECD test guideline 421 (developmental/reproductive screening assay). 

The summary of this study is presented below. 

Groups of 10 rats (Crl:CD (SD) BR) per sex were treated with dosages of 0, 12.5, 50, and 150 

mg/kg bw/day by gavage (administration volume 10 ml/kg bw/day) using sesame oil as a 

vehicle. Males were treated daily from 14 days prior to mating until the end of the mating period 

for a maximum of 28 days. Females were treated daily for 14 days before start of the mating 

period, throughout the same, during pregnancy and until day 3 of lactation. The animals were 

mated one male with one female. 

At daily doses of 150 mg/kg bw 6/10 males and 5/10 females died between day 9 and day 25 of 

treatment (during the premating and mating period). At daily doses of 50 mg/kg bw 1/10 males 

and 1/10 females died on day 13 respectively on day 24 of treatment. No animals died at 12.5 

mg/kg bw/day, and in the control group 1 female died by accident. 
Page 72 of 103

Clinical observations at 150 mg/kg bw/day revealed salivation after treatment, hunched posture 

and in some cases soft stools and piloerection. The only clinical sign present at 50 mg/kg bw/day 

was salivation. No changes were seen at 12.5 mg/kg bw/day. 

Body weight loss of about 22 g at the 150 mg/kg bw dose group and statistically significant (p > 

0.01) lower body weight gain at the 50 mg/kg bw dose group during the premating period 

together with a lower mean food consumption was observed in the males. Also in the females 

body weight loss of about 17 g at the 150 mg/kg bw dose group and statistically significant lower 

body weight gain at the 50 mg/kg bw dose group together with a lower mean food consumption 

during the premating period was observed. 

At sacrifice of the parental animals organ weights of ovaries, testes and epididymides were 

determined from all experimental groups. Histopathology was carried out on testes, 

epididymides and ovaries of the controls and of the animals of the 150 mg/kg bw dose group. A 

statistically significant (p> 0.01) lower absolute and relative weight of epididymides and a 

statistically significant (p> 0.01) higher value of relative testis weight was observed at 150 

mg/kg bw/day. No significant differences were noted in ovary weights among the various 

experimental groups. Histopathology of testes and epididymides of high dose group animals did 

not show any compound-related changes. In particular, no changes were seen in the testicular 

staging performed in the PAS-hematoxylin stained sections of final sacrificed animals of control 

and of the high dose groups. In the ovaries, moderate increased frequency of atrophic corpora 

lutea was seen in the animals of the high dose group which died or were sacrificed, compared to 

the controls, this finding was considered a secondary effect to the decrease in body weight 

growth induced by treatment in this group. At the dosages of 150 mg/kg bw/day only 3 females 

out of 7 mated females had positive vaginal smears and of these only one was pregnant, but with 

only implantation sites and no live pups. At this dosage level also the mean pre-coital interval 

was longer (13.4 days) than that of the control group (2.3 days). With regard to the mating index 

in the control, the 12.5 and the 50 mg/kg bw dose level groups 9/9 (100%), 9/10 (90%) and 9/9 

(100%) mated females were sperm positive. With regard to the fertility index 9/9 (100%), 8/10 

(80%) and 7/9 (78%) of the mated females became pregnant in the control, the 12.5 and the 50 

mg/kg bw dose level groups. Mean pre-coital time and parturition were unaffected in the low and 

mid dose treated groups. 

With regard to the conception rate in the control, the 12.5 and the 50 mg/kg bw dose level groups 

9/9 (100%), 8/9 (89%) and 7/9 (78%) of the sperm positive females became pregnant and 

delivered live pups. Numbers of corpora lutea had not been determined during this study. Thus, 

any pre-implantation loss was not evaluated. Staining for the presence of implantation sites was 

only performed with the uteri of apparently non-pregnant females. The mean number of visible 

implantation sites per dam in the control, the 12.5 and the 50 mg/kg bw dose level groups were 

17.6, 13.9 and 15.0. There were no stillborns or litters with only implantations in the control, 
Page 73 of 103

low, and mid dose groups. The mean number of total pups born per litter was 16.9, 12.3 and 14.3 

in the control, the 12.5 and the 50 mg/kg bw/day dose groups. Thus, the mean litter index for 

post-implantation loss was calculated to 3.4, 9.9 and 4.5% in the control, the low and the mid 

dose groups. 

No effects were noted on the pup sex ratio. No abnormalities were observed in any pup either at 

birth or at autopsy on day 4 of lactation neither in the 12.5 nor in the 50 mg/kg bw/day treated 

groups. Lower mean values of live born per litter and of pups per litter alive at day 4 were found 

for both the low and the intermediate dose groups in comparison to those of the control group, 

however, the decreases were not dose dependent and the differences were statistically significant 

for the 12.5 mg/kg bw dose group only. Thus, these findings were considered unlikely to be 

related to the compound. A slightly lower pup body weight was observed in the 50 mg/kg 

bw/day treated group in comparison with the control group at birth and at day 4 of lactation but 

not for the pups of the 12.5 mg/kg bw/day treated group. 

Based on findings of general toxicity (death, clinical signs, reduced body weight gain) at 

daily dosages of 50 mg/kg bw/d a NOEL/systemic toxicity of 12.5 mg/kg bw/d can be 

derived from the study. Based on the findings of a lower fertility index and a lower 

conception rate at daily dosages of 50 mg/kg bw/d a NOEL/fertility of 12.5 mg/kg bw/d can 

be derived from the results of this screening study. 

In addition to the above cited study, a combined repeated dose toxicity study with 

reproduction/developmental toxicity screening (performed according to OECD guideline 422) 

was conducted with coco alkylamine (CAS # 61788-46-3) and was submitted and reviewed by 

the Office of Pesticide Programs (MRID 47646101). Coco alkyl amine was assessed as part of a 

risk assessment conducted in 2009 by the Health Effects Division of OPP for inert uses of a 

group of primary alkyl amines in pesticide formulations. Note that coco alkylamine is a 

chemical listed in the 2008 European Union risk assessment, but is not listed in the OPP RED for 

alkyl trimethylenediamines. 

Structure: 
Page 74 of 103

Study summary 

In a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening 

Test (MRID 47646101), Amines, coco alkyl (CAS # 61788-46-3; Batch # 830668; 100.4% a.i.) was 

administered to 10 Crl:CD(SD) rats/sex/dose by gavage at dose levels of 0, 5, 20, 40 or 80 mg/kg bw/day. 

The vehicle and diluent were reverse osmosis deionized water and glacial acetic acid, respectively. 

Dosing began 14 days before the cohabitation period and continued through the day before sacrifice. 

Surviving male rats received at least 46 doses. For female rats, dosing continued through lactation day 

(LD) 4 for rats that delivered a litter or GD 24 for rats that did not deliver a litter. Females received a total 

of 38-42 doses. Five animals/sex/group were tested in the FOB followed by motor activity testing on the 

day of scheduled sacrifice. 

Two high-dose males were sacrificed moribund, one each on study day 18 and 42. Clinical signs in these 

animals included rales, salivation, urine staining, weight loss/emaciation, ungroomed 

coat, dyspnea, and gasping; at necropsy gavage error was confirmed for one animal, but a cause of death 

was not determined for the other animal. Treatment-related clinical signs of toxicity in the 40- and 80-

mg/kg/day males included rales in 8 and 10 animals, respectively, and excessive salivation in 5 and 8 

animals, respectively. Among female rats, clinical signs of toxicity included excessive salivation in 1 and 

2 animals, respectively during premating, in 1 and 4 animals, respectively, during gestation, and in 0 and 

1 animal, respectively, during lactation. 

Body weight, body weight gain, and food consumption by the 5- and 20-mg/kg/day groups was similar to 

the control group levels throughout the study. Body weight gain was slightly or significantly less than that 

of controls for the 40-mg/kg/day males beginning on the third week of the study and for the 80-mg/kg/day 

males from the beginning of the study. Mean weekly body weight gains for the 40- and 80-mg/kg/day 

males were 5-87% and 35-71%, respectively, of the control group level resulting in an overall weight 

gain for the study 65% and 20%, respectively, of the control level. The high-dose group showed a mean 

weight loss for the day 36-43 and 43- 46 intervals. Final body weight of the 40- and 80-mg/kg/day males 

was 92 and 81% of the control value. Food consumption by the 40-mg/kg/day males was significantly 

less than that of the control group during days 36-43 (p 0.05; 87% of control). Food consumption by the 

80- mg/kg/day males was significantly less than that of the controls during days 29-36, 36-43, and overall 

(p 0.05 or 0.01; 69-85% of controls). 

For females during premating, body weight, weight gain, and food consumption were similar between the 

treated and control groups. Body weight and weight gain were not affected during gestation. Food 

consumption by the high-dose females during gestation was significantly less than that of controls for 

GDs 0-12 and overall (p 0.05 or 0.01; 83-85% of control level). During lactation, body weight of the 

high-dose group was significantly less than that of controls on days 3 and 4 (p 0.05; 90% of control level). 

Body weight changes during lactation were highly variable for all treated and control groups. Food 

consumption by the high-dose group during lactation days 1-4 was 79% of the control level but did not 

attain statistical significance. 
Page 75 of 103

During the FOB, no treatment-related changes in home cage, handling, or open field behavior were 

observed. Sensory reactions, grip strengths, air righting response, and landing foot splay were similar 

between the treated and control groups for males and females. High-dose males had markedly reduced 

number of movements and time spent in movement (overall 50% and 42%, respectively, of control 

levels). In general, both parameters were reduced after the first 20 minutes and for the remainder of the 

session. Statistical significance was not attained due to large variability in the data. No differences 

between treated and control females were seen for motor activity. 

No biologically important differences were observed in the male or female rats at doses up to 80 

mg/kg/day in the hematology or clinical chemistry parameters. At necropsy, terminal body weight and 

absolute and relative (to brain) liver, kidney, and heart weights were significantly (pO.O5 or 0.01) 

reduced in the 80-mg/kg/day males. High-dose males also had significantly reduced organ weightrelative-to-body weight of the testes, brain, and adrenals, although the absolute weight of these organs 

was similar to the control group value. No clear effects on organ weight were seen in female rats. No 

treatment-related gross lesions were observed in male or female rats at terminal sacrifice. 

Microscopically, a dose-related increase in the incidence and severity of erosions, 

hyperplasia/hyperkeratosis, and necrosis was observed in the stomach of males and females administered 

20 mg/kg/day and higher. Thymic atrophy was found in 80-mg/kg/day males and females and in the 20- 

and 40-mg/kg/day females. Dose-related increases in the incidence and severity of macrophage 

infiltration occurred in the ileum of males at the two highest doses, in the jejunum of males at >20 

mg/kg/day and in females at 40 and 80 mg/kg/day, in the liver of high- dose males and females, and in the 

mesenteric lymph node of males at >20 mg/kg/day and in females at 40 and 80 mg/kg/day. In the lymph 

node and liver of affected animals, the macrophages coalesced to form microgranulomas. 

Estrous cycling was similar between the treated and control groups. The mean number of cycles for all 

groups was 2.4-2.8 during the premating interval. Reproduction and fertility were not affected by 

treatment. The mean duration of gestation and the mean number of implantation sites and corpora lutea 

were similar between the treated and control groups. 

Litter size and mean number of pups at first litter check and the sex ratio were not affected by treatment. 

Pup survival was similar between the treated and control groups. No treatment- related clinical signs of 

toxicity were observed in the pups during lactation. Offspring body weight for the 40 and 80 mg/kg/day 

groups was significantly less than that of the controls on lactation days 1 and 4. Body weight gain was 

markedly decreased at 80 mg/kg/day for lactation days 1-4 (1.8 g vs 3.0 g for controls). No treatmentrelated findings were noted on macroscopic examination of the pups. 
Page 76 of 103

The parental /systemic LOAEL for amines, coco alkyl in rats is 20 mg/kg/day based on 

microscopic lesions in the stomach, jejunum, thymus, and lymph node in males and 

females. The parental/ systemic NOAEL is 5 mg/kg/day. 

The reproductive/developmental LOAEL for Amines, coco alkyl in rats is 40 mg/kg/day, 

based on decreased body weight and body weight gain in male and female offspring. The 

reproductive/developmental NOAEL is 20 mg/kg/day. 

This study is classified Acceptable/Guideline and satisfies the guideline requirement for a Combined 

Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test 

(OECD 422) in the rat (OPPTS 870.3650). 

Chronic Toxicity

The registrant submitted no data on the chronic toxicity of the active ingredient under 

consideration (N-(coco alkyl)trimethylenediamine [also referred to as N-coco 1,3-

diaminopropane]). Instead, the registrant cited three chronic toxicity studies performed with 

octadecylamine (stearamine). The studies cited by the registrant are summaries within the 2008 

European Union Risk Assessment document. The structure of the chemical and summaries of 

these studies (all that was provided) are shown below. 

Structure: 

 
Page 77 of 103

STUDY SUMMARIES

One chronic study involved the administration of stearic acid, a metabolite of hydrogenated 

tallow alkylamines at a single dose of approximately 200 mg/kg/day for 206 days in the diet. 

Another group was fed with diet containing octadecylamine that was dissolved in corn oil (CAS 

124-30-1), while a control group was not carried along. Food consumption and the weekly 

change of body weights were recorded. Gross and microscopic examinations were made on 

major tissues (20 organs/tissues). 

Two out of five female rats died spontaneously (no details were provided). Average weight gain 

was 12 g in males and 58 g in females, and the animals were reported to be anorexic. Tissues 

from rats fed with stearic acid showed severe pulmonary infection consisting of 

tracheobronchitis, lobular pneumonia, lipoid histiocytic response, and abscess formation. No 

histomorphologic abnormalities were observed in the other organs. The authors concluded 

anorexia and increased mortalities as being substance-related toxic effects of stearic acid. This 

study used one dose and is therefore limited in its hazard characterization. 

In a second study, four groups of 24 rats (12/sex) were fed diets containing 20, 100, 200, and 500 

ppm stearamine for two years (mean dose was about 1.05, 5.79, 10.68, and 27.15 mg/kg/day for 

350 g males and 1.20, 5.80, 10.08, and 28.20 mg/kg/day for 250 g females). Feed consumption, 

growth rate, death rate, and blood cell counts for the experimental animals were comparable to 

those of the control animals. Tissues examined by histopathology examination included brain, 

viscera, gonads, skeletal muscle, bone marrow, heart, lungs, liver, spleen, kidneys, gastroenteric 

tract (3 levels), pancreas and lymph nodes. The organs examined microscopically included the 

heart, lungs, liver, spleen, kidneys, gastrointestinal tract (3 levels), pancreas, lymph nodes, bone 

marrow, brain, pituitary, adrenals, and ovary or testis. The feed consumption, growth rate, death 

rate, and blood cell counts for the experimental animals were comparable to those of the control 

animals. One rat receiving 500 ppm showed histiocytic hyperplasia of the mesenteric lymph 

node. At necropsy, no significant differences were found between the experimental and control 

groups in the incidence and types of lesions observed. Having the histiocytic accumulations at 

3000 ppm (seen in the 209 day-study in rats) and lesions of the same nature in the dog in mind, 

the single case of histiocytic hyperplasia in the mesenteric lymph node of the single rat treated 

with 500 ppm (25 mg/kg bw/d) for 2 years (in this study) could also be interpreted as a 

treatment-related. Therefore a NOAEL of 200 ppm (10 mg/kg bw/d) is proposed for the 2-

year rat studies. 

In a third study, three groups of three dogs (2 females and 1 male or 2 males and 1 female) each 

were fed 0.6, 3.0, and 15.0 mg/kg bw/d octadecylamine ("stearamine") in corn-oil solution that 

was administered by capsule once daily (5 d/wk) A control group of dogs was given untreated 

feed. Dogs were housed in individual cages and fed once daily. Hematological examinations 
Page 78 of 103

consisted of total red blood cell count, hemoglobin concentration, total and differential white cell 

counts and were performed on all dogs at the start of the experiment and at 1, 2, 3, 6, 8, 11, and 

12 months thereafter. The organs examined microscopically included the heart, lungs, liver, 

spleen, kidneys, gastroenteric tract (3 levels), pancreas, lymph nodes, bone marrow, brain, 

pituitary, adrenals, and ovary or testis. The high dose group gained less weight than the control 

and lower-dose animals. The weight gain for the two lower-dose groups was similar to that of the 

controls. Blood cell counts were comparable in experimental and control animals. Only one dog 

died before study termination (after week 22); this dog was from the group receiving 15.0 mg/kg 

bw/d octadecylamine and suffered from anorexia, bloody diarrhea and what appeared to be 

gastroenteric irritation. At necropsy, two animals from the high-dose group had lesions 

suggestive of the mesenteric lymph nodes, which were filled with pale histiocytes. Also, pale 

staining of the tips of the villi of the small intestine mucosa was observed in these dogs. 

However, no definite lesions were identified in the intestinal tracts of these animals or in any of 

the other experimental animals. [No other information available.] Considering the mortality 

associated with anorexia and hemorrhagic diarrhea in one dog, growth depression in two other 

dogs, and the lymph node histiocytosis observed at 15 mg/kg bw/d as a treatment-related toxic 

effect, the NOAEL in dogs fed with octadecylamine (CAS 124-30-1) for 1 year was 3 mg/kg 

bw/d. 

Carcinogenicity

The registrant did not submit any carcinogenicity data for the active ingredient N-(cocoalkyl)trimethylenediamine, but instead cited a study in the 2008 European Union risk assessment 

conducted on octadecylamine. The summary of that study is shown below, as printed in the 2008 

European Union risk assessment. 

“A 2-year toxicity study of octadecylamine ("stearamine") was conducted using SpragueDawley rats. Four groups of 24 rats (12/sex) were fed diets containing 20, 100, 200 and 500 ppm 

stearamine (reviewed by Pang, 1995, original data University of Miami, 1957, Deichmann et al., 

1958). A control group of animals was fed the base diet alone. The feed consumption, growth 

rate, death rate, and blood cell counts for the experimental animals were comparable to those of 

the control animals. The survival rate for this study was 17-33% including the control group. At 

necropsy, no significant differences were found between the experimental and control groups in 

the incidence and types of lesions observed. No significant increase occurred in the incidence of 

lesions. [No other information available.]” 

While this summary provides little information on carcinogenicity, there are additional pieces of 

information that would support the lack of carcinogenic potential for these chemicals. The first 

piece of information is the mutagenicity database for the alkyl amine compounds assessed in the 
Page 79 of 103

2008 European Union risk assessment, where the data show these chemicals to be negative for 

mutagenicity in a variety of assays. The second piece of information available is a structureactivity analysis conducted by OPP’s Health Effects Division as part of the 2009 risk assessment 

for linear alkyl amines as inerts in pesticide formulations. Using the DEREK software program 

for prediction of structural alerts that may indicate concern for carcinogenicity, there were no 

identified structural alerts of concern for the chemicals screened. The third piece of information 

available are mutagenicity data cited in the alkyl trimethylenediame RED that also showed 

negative results for mutagenicity. 

The fourth piece of information is an analysis conducted for the N-alkyl amines and the alkyl 

diamines (collectively known as aliphatic amines) using the Oncologic SAR program. This 

analysis was conducted by the Office of Pollution Prevention and Toxics, one of the major 

program offices within the Office of Chemical Safety and Pollution Prevention. Their analysis 

states in part, ” unlike aromatic amines, aliphatic amines are generally not considered to have 

significant carcinogenic activity unless the alkyl group is small and contains reactive groups 

(e.g., terminal Cl/Br/I) or pro-reactive groups (e.g., unhindered terminal double bond). Although 

hydroxylamines of aliphatic amines can be reactive, they are usually too short-lived to have 

effects beyond local action.” 

 
Page 80 of 103

APPENDIX C: ECOTOXICITY DATA

 Acute and chronic toxicity data from registrant-submitted studies conducted in 

accordance with the 850 OCSSP Harmonized Test Guidelines are used to evaluate the potential 

acute and chronic effects of ATMD to nontarget organisms. The available ecotoxicity endpoints 

from studies submitted by registrants are tabulated below. OPP uses the most sensitive of these 

endpoints (see Table 6) for assessing risk to each terrestrial and aquatic receptor group. 

Additionally, Web-ICE40 (EPA 2013) has been used to predict the acute toxicity to the fathead 

minnow and to cyanobacteria. Predicting the fathead LC50 allows for developing an AcuteChronic Ratio41 (ACR; EPA 2010) for freshwater fish and subsequently predicting a chronic 

NOAEC for the rainbow trout, the most acutely sensitive freshwater fish (Table 23). As 

presented in Table 25 and Table 26, ACRs also were calculated and used to extrapolate NOAECs 

for estuarine/marine invertebrates and estuarine/marine fish for which ecotoxicity studies were 

not submitted. 

Toxicity to Terrestrial Organisms

Birds

 Two acceptable and three supplemental acute-oral (LD50) studies categorize the AMTDs 

as being practically nontoxic to very highly toxic to birds (Table 22). The guideline (850.2100) 

is satisfied. 

 

40 To address data gaps in species sensitivity, the Interspecies Correlation Estimations (ICE) application was 

developed by EPA and collaborators to extrapolate acute toxicity to taxa with little or no acute toxicity data for a 

chemical (EPA 2013). ICE models estimate the acute toxicity (LC50/LD50) of a chemical to a species, genus, or 

family with no test data (the predicted taxon) from the known toxicity of the chemical to a species with test data (the 

surrogate species). ICE models are least square regressions of the relationship between surrogate and predicted 

taxon based on a database of acute toxicity values: median effect or lethal water concentrations for aquatic species 

(EC/LC50; μg/L) and median lethal oral doses for wildlife species (LD50; mg/kg bodyweight). 

41 An Acute-Chronic ratio (ACR) can be used to predict chronic toxicity in aquatic organisms when the acute 

toxicity is known but chronic data are absent or limited/indefinite (USEPA 2010). OPP derives ACRs for pesticides 

based on the ratio of the acute toxicity of a chemical (expressed as an LC50 or EC50 value from a valid acute study) 

to its chronic toxicity (expressed as a NOAEC value from a valid chronic study). Ideally, the acute and chronic 

toxicity data used to derive the ACR should be from the same test species. This ACR is then applied to a species 

within a similar group (e.g., estuarine/marine fish). 
Page 81 of 103

Table 22: Avian Acute-Oral Toxicity 

Test Species Test Material 

(% ai) Toxicity Toxicity Category

EPA Study 

ID

Northern bobwhite 

(Colinus virginianus) 

100 LD50 = 0.24 mg ai/kg 

bw Very highly toxic 470013023 Acceptable

Not reported LD50 = 492 mg ai/kg 

bw Moderately toxic 97534 Acceptable 

23.5 LD50 = 500 mg ai/kg 

bw Moderately toxic 106859 Supplemental

22 LD50 = 681 mg ai/kg 

bw Slightly toxic 134550 Supplemental

Mallard 

(Anas platyrhynchos) 22 LD50 = 3200 mg ai/kg 

bw Practically nontoxic 110384 Supplemental 

 Eight available dietary (LC50) studies categorize the AMTDs as being practically 

nontoxic to slightly toxic birds when administered in the diet (Table 23). No additional data are 

needed for this guideline (850.2200). 

Table 23: Avian Dietary Toxicity 

Test Species Test Material 

(% ai) Toxicity Toxicity Category

EPA Study 

ID

Northern bobwhite 

(Colinus virginianus) 

100 LC50 = 6400 ppm Practically 

nontoxic 

470013024 

Acceptable

32 LC50 = 6400 ppm Practically 

nontoxic 

40062405 

Acceptable 

0.03 LC50 >10,000 ppm Practically 

nontoxic 

123864 

Acceptable 

Not reported LC50 = 5000 ppm Practically 

nontoxic 

97535 

Supplemental

Mallard 

(Anas platyrhynchos) 50 LC50= 5000 ppm Slightly nontoxic 133266

Acceptable 

0.03 LC50 = 100,000 ppm Practically 

nontoxic 

123863 

Acceptable 

32 LC50= 6400 ppm Practically 

nontoxic 

470013025 

Supplemental 

Not reported LC50 = 5000 ppm Practically 

nontoxic 

97516 

Supplemental
Page 82 of 103

Nontarget Insects  

 Toxicity data for beneficial insects (850.3020, 850.3030) are not required for this use 

pattern. 

Toxicity to Aquatic Organisms

Freshwater Fish  

 The available acute toxicity studies categorize the AMTDs as being slightly to highly 

toxic to freshwater fish (Table 24). The guideline (850.1075) for acute toxicity testing is 

satisfied. 

Table 24: Freshwater Fish Acute Toxicity 

Test Species Test Material 

(% ai) 

Toxicity Endpoint 

(mg ai/L) 

Toxicity 

Category 

EPA Study 

ID 

Rainbow Trout 

(Oncorhynchus mykiss) 32 96-hr LC50 = 0.12 Highly toxic 41786606 Acceptable

0.03 96-hr LC50 = 1300 Slightly toxic 123862 

Acceptable

Not reported 96-hr LC50 = 1.58 Moderately 

toxic 

97518 

Supplemental

Bluegill 

(Lepomis macrochirus) 50 96-hr LC50 = 0.3 Highly toxic 133265 

Acceptable

32 96-hr LC50 = 0.96 Highly toxic 

41786601 

Acceptable 

32 96-hr LC50 = 0.3 Highly toxic 41786601 

Supplemental 

0.03 96-hr LC50 = 1390 Practically 

nontoxic 

123862 

Acceptable

 Chronic data are available for the fathead minnow. Based on the ACR for the fathead 

minnow (acute toxicity predicted from Web-ICE, EPA 2013) and the acute toxicity value for the 

rainbow trout, the most acutely sensitive freshwater fish species, an NOAEC value of 0.004 mg 

ai/L was determined for the rainbow trout. No additional chronic data are needed (fish early-life 

stage, 850.1400). 
Page 83 of 103

Table 25: Freshwater Fish Chronic Toxicity 

Test Species Test Material 

(% ai) 

NOAEC 

(mg ai/L) 

LOAEC 

(mg ai/L) 

EPA Study 

ID 

Fathead minnow 

(Pimephales 

promelas)

94.1 0.011 0.023 49040209 

Acceptable

Rainbow Trout 

(Oncorhynchus mykiss)

NA 0.004a nd 49208804 

Acceptable

a

 The rainbow trout was the most acutely sensitive fish species tested but no chronic data are available for this 

species; therefore, a chronic NOAEC was estimated for the trout. The chronic value was extrapolated using an 

acute-chronic ratio (ACR; EPA 2010) of 29 as determined by using the fathead minnow LC50 (328 μg ai/L as 

predicted from Web-ICE; EPA 2013, see Appendix C), fathead minnow NOAEC (11 μg ai/L), and the rainbow trout 

LC50 (120 μg ai/L) 

Freshwater Invertebrates 

 The four available acute toxicity studies for the waterflea categorize the AMTDs as being 

highly to very highly toxic to freshwater invertebrates (Table 26). One chronic study found no 

adverse effects on daphnid reproduction or growth but mortality occurred at 0.016 mg ai/L. The 

guidelines for acute (850.1010) and chronic (850.1300) toxicity testing are satisfied. 

Table 26: Freshwater Invertebrates Acute and Chronic Toxicity 

Test Species Test Material 

(% ai) 

Toxicity Endpoint 

(mg ai/L) 

Toxicity 

Category 

EPA Study 

ID 

Waterflea 

(Daphnia 

magna) 

32 48-hr EC50 = 0.051 Very highly toxic 

41786602 

 Acceptable 

32 48-h EC50 = 0.16 Highly toxic 41786602 

Acceptable

32 48-h EC50 = 0.104 Highly toxic 40062409 

Acceptable 

Not reported 48-h EC50 = 0.12 Highly toxic 97521 

Supplemental 

94.1 Chronic NOAEC = 0.016 

Chronic LOAEC = 0.054 NA 490402-08Acceptable 
Page 84 of 103

Estuarine/Marine Fish and Invertebrates 

 The available estuarine/marine acute toxicity studies categorize AMTD as being highly to 

very highly toxic to fish and practically nontoxic to very highly toxic to invertebrates (Table 27). 

The guidelines for acute testing with a fish (850.1075), a bivalve (850.1025 or 850.1055), and 

one additional invertebrate (850.1035) are satisfied. Chronic data were not submitted, but ACRs 

were used to extrapolate chronic NOAECs for fish and crustaceans. The predicted NOAECs 

indicate that chronic effects may occur at ATMD concentrations in the parts per billion (Table 

27). Additional chronic data (850.1300) are not needed. 

Table 27: Estuarine/Marine Invertebrates Acute and Chronic Toxicity 

Test Species Test Material 

(% ai) 

Toxicity Endpoint 

(mg ai/L) 

Toxicity 

Category 

EPA Study 

ID 

Atlantic silverside 

(Menidia menidia) 32 96-hr EC50 = 0.155 Highly toxic 

41786604 

Acceptable 

32 48-h EC50 = 0.577 Highly toxic 41786604 

Acceptable

NA Chronic NOAEC = 0.005a NA NA 

Mysid shrimp 

(Mysidopsis bahia) 32 96-h EC50 = 0.019 Very highly toxic 41786605 

Acceptable 

NA Chronic NOAEC = 0.019b NA NA 

Quahog clam 

(Mercenaria mercenaria) 32 48-h EC50 = 0.019 Very highly toxic 41786603 

Acceptable 

White shrimp 

(Penaeus setiferus) 32 96-h EC50 = 2.39 Moderately toxic 40062411 

Supplemental 

Eastern oyster 

(Crassostrea virginica) 32 96-h EC50 = 720 Practically nontoxic 40062412 

Acceptable 

Pink shrimp 

(Penaeus duorarum) 0.03 96-h EC50 = 1000 Practically nontoxic 123866 

Acceptable 

Fiddler crab 

(Uca pugilator) 0.03 96-h EC50 = 1000 Practically nontoxic 123866 

Acceptable 
Page 85 of 103

Test Species Test Material 

(% ai) 

Toxicity Endpoint 

(mg ai/L) 

Toxicity 

Category 

EPA Study 

ID 

Blue crab 

(Callinectes 

trimethylenedi) 

Not reported 96-h EC50 = 387 Practically nontoxic 97520 

Supplemental 

a

 The NOAEC is extrapolated from the ACR (29) for freshwater fish (see footnote a) and LC50 of 155 μg ai/L for 

the Atlantic silverside; the extrapolation assumes a common chronic mode of action for freshwater and 

estuarine/marine fish 

b

 The NOAEC is extrapolated from the ACR (3) for freshwater invertebrates (LC50 = 51 μg ai/L, NOAEC = 16 μg 

ai/L) and the acute toxicity for the estuarine/marine crustacean (mysid shrimp LC50 = 61 μg ai/L); the extrapolation 

assumes a common chronic mode of action for freshwater and estuarine/marine invertebrates

Aquatic Plants 

 Aquatic plant toxicity data are presented in Table 28. Studies available for the TGAI 

include a toxicity test with duckweed, a vascular species (850.4400), and algal toxicity tests 

(850.4500) with green algae (2 spp.), a freshwater diatom, and a marine diatom. Web-ICE was 

used to predict the toxicity of cyanobacteria (850.4550). No additional testing is needed. 

Table 28: Aquatic Plant Toxicity 

Test Species Test Material 

(% ai) 

Toxicity Endpoint 

(mg ai/L) 

EPA Study 

ID 

Duckweed 

(Lemna gibba) 94.1 7-d EC50 = 0.123 NOAEC = 0.020 

49040213 

Acceptable

Green algae 

(Pseudokirchneriella subcapitata) 94.1 96-h EC50 = 0.0052 

NOAEC = 0.0024

49040216 

Acceptable 

Green algae 

 (Scenedesmus subspicatus) 94.1 96-h EC50 = 0.011 

NOAEC = 0.0069 

49040217 

Acceptable 

Freshwater diatom 

(Navicula pelliculosa) 94.1 96-h EC50 = 0.017 

NOAEC = 0.009 

49040215 

Acceptable 

Marine Diatom 

(Skeletonema costatum) 94.1 96-h EC50 = 0.011 

NOAEC = 0.008 

49040214 

Acceptable 

Cyanobacteria 

(Anabaena flos-aquae) -- 96-h EC50 = 0.007a 49208807 

Supplemental 

a

 predicted from the Web-ICE Algae Module (EPA 2013) using Pseudokirchneriella subcapitata as a surrogate 

species 

Subchronic sediment toxicity 

 Two subchronic studies are available (Table 29). One study tested the freshwater midge 

(850.1735) and another study tested the estuarine/marine amphipod (850.1740). A data gap 

exists for a subchronic test for the freshwater amphipod (850.1735). Lack of toxicity for the 
Page 86 of 103

second freshwater species adds uncertainty to the risk assessment for freshwater benthic 

invertebrates. 

Table 29: Subchronic Sediment Toxicity 

Test Species Test Material 

(% ai) 

Toxicity Endpoint 

(mg ai/kg sediment) 

EPA Study 

ID 

Freshwater Midge 

(Chironomus tentans) 94.1 10-d EC50 = 188 NOAEC = 16 

49040211 

Acceptable

Marine Amphipod 

(Leptocheirus plumulosus) 94.1 10-d EC50 = 303 

NOAEC = 174 

49040212 

Acceptable 

Ecotoxicity References 

EPA. 2013. Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: 

User Manual (version 3.2). EPA/600/R-12/603. USEPA Office of Research and Development, 

Gulf Ecology Division, Gulf Breeze, FL http://www.epa.gov/ceampubl/fchain/webice/

EPA. 2010. Predicting the Toxicities of Chemicals to Aquatic Animal Species. USEPA Office 

of Water and Office of Pesticide Programs, Washington, DC; Office of Research and 

Development, Gulf Ecology Division; and Office of Research and Development, Mid-Continent 

Ecology Division. October 27, 2010. 

MRID 41786602 Surprenant, D. 1988. Acute Toxicity of Microbiocide 56 to Daphnids (Daphnia 

magna): Lab Project Number: 88-3-2669: 384.1187.6100.110. Unpublished study prepared by Springborn 

Life Sciences, Inc. 20p. 

MRID 41786603 . Surprenant, D. 1988. Acute Toxicity of Microbiocide 56 to Embryo-Larvae of the 

Quahog Clam (Mercenaria mercenaria) Under Static Renewal Conditions: Lab Project Number: 88-5-

2712. Unpublished study prepared by Springborn Life Sciences, Inc. 20p. 

MRID 41786604 Surprenant, D. 1988. Acute Toxicity of Microbiocide 56 to Silversides (Menidia 

menidia) Under Static Renewal Conditions: Lab Project Number: 88-4-2687: 384.1187.6100.501. 

Unpublished study prepared by Springborn Life Sciences, Inc. 19p. 

MRID 41786605.Surprenant, D. 1988. Acute Toxicity of Microbiocide 56 to Mysid Shrimp 

(Mysidopsis bahia): Lab Project Number: 88-4-2739: 384.1187.6100.510. Unpublished study 

prepared by Springborn Life Sciences, Inc. 20p. 

MRID 41786606 Surprenant, D. 1990. Acute Toxicity of Microbiocide 56 to Rainbow Trout 

(Salmo gairdneri) Under Static Conditions: Lab Project Number: 88-11-2861: 384.0788.6101.103. 

Unpublished study prepared by Springborn Life Sciences, Inc. 19p. 

MRID 40062404. Bisinger, E. (1984) Avian Oral LD50 in Bobwhite Quail: Wildlife and Aquatic 

Organism Data Requirements: Armohib B-101: Report No. T-4000: [Supplemental Data Submitted in 

Response to EPA’s Comments]. Unpublished study prepared by Akzo Chemie America and Product 

Safety Labs. 14p. 
Page 87 of 103

MRID 40062405. Bisinger, E. (1984) Avian Dietary LC50 in Bobwhite Quail: Wildlife and Aquatic 

Organism Data Requirements: Armohib B-101: Report No. T-3995: [Supplemental Data Submitted in 

Response to EPA’s Comments]. Unpublished study prepared by Akzo Chemie America and Product 

Safety Labs. 13p. 

MRID 40062609. Bisinger, E. (1984) Acute LC50: Daphnia magna: Wildlife and Aquatic Organism 

Data Requirements: Armohib B-101: Report No. H-8241: [Supplemental Data Submitted in Response to 

EPA’s Comments]. Unpublished study prepared by Akzo Chemie America and MBA Laboratories. 14p. 

MRID 40062411. Bisinger, E. (1984) Acute LC50 in Estuarine and Marine Organisms/96-hour LC50 in 

White Shrimp: Wildlife and Aquatic Organism Data Requirements: Armohib B-101: Report No. H-8241: 

[Supplemental Data Submitted in Response to EPA’s Comments]. Unpublished study prepared by Akzo 

Chemie America and MBA Laboratories. 14p. 

MRID 40062412. Bisinger, E. (1984) Acute LC50 in Estuarine and Marine Organisms/96-hour LC50 in 

Oyster: Wildlife and Aquatic Organism Data Requirements: Armohib B-101: Report No. H-8241: 

[Supplemental Data Submitted in Response to EPA’s Comments]. Unpublished study prepared by Akzo 

Chemie America and MBA Laboratories. 14p. 

MRID 49040208 Minderhout, T. et al. 2012. DUOMEEN C: A Flow-through Life-cycle Toxicity Test 

with the Cladoceran (Daphnia magna). Wildlife International, Ltd. Project No.: 709A-108A. Mexel 

Industries, SAS: C/O Mexel USA, LLC. 

MRID 49040209 Minderhout, T., K. et al. 2012. DUOMEEN C: An Early Life-Stage Toxicity Test with 

the Fathead Minnow (Pimephales promelas). Wildlife International, Ltd. Project No.: 709A-109A. 

Mexel Industries, SAS: C/O Mexel USA, LLC. 

MRID 49040211 Thomas, S. et al. 2013. DUOMEEN C: A 10-day Survival and Growth Toxicity Test 

with the Midge (Chironomus tentans) Using Spiked Sediment. Wildlife International, Ltd. Project No: 

709A-106. Study sponsored by Mexel Industries, SAS C/O Mexel USA, LLC. 

MRID 49040212 Thomas, S. et al. 2013. DUOMEEN C: A 10-day Survival Test with the Marine 

Amphipod (Leptocheirus plumulosus) Using Spiked Sediment. Wildlife International, Ltd. Project No: 

709A-107A. Study sponsored by Mexel Industries, SAS C/O Mexel USA, LLC. 

MRID 49040213 Jacobs, A. et al. 2012. DUOMEEN C: A 7-Day Static-Renewal Toxicity Test with 

Duckweed (Lemna gibba G3). Wildlife International, Ltd. Project No: 709A-101. Study sponsored by 

Mexel Industries, SAS C/O Mexel USA, LLC. 

MRID 49040214 Jacobs, A. et al. 2012. DUOMEEN C: A 96-hour Toxicity Test with the Marine 

Diatom (Skeletonema costatum). Wildlife International, Ltd. Project No: 709A-104. Study sponsored by 

Mexel Industries, SAS C/O Mexel USA, LLC. 

MRID 490402-15 Jacobs A. et al. 2012. DUOMEEN C: A 96-hour Toxicity Test with the Freshwater 

Diatom (Navicula pelliculosa). Wildlife International, Ltd. Project No: 709A-105. Study sponsored by 

Mexel Industries, SAS C/O Mexel USA, LLC. 
Page 88 of 103

MRID 49040216 Jacobs, A. et al. 2012. DUOMEEN C: A 96-hour Toxicity Test with the Freshwater 

Alga (Pseudokirchneriella subcapitata). Wildlife International, Ltd. Project No: 709A-102. Study 

sponsored by Mexel Industries, SAS C/O Mexel USA, LLC. 

MRID 49040217 Jacobs, A. et al. 2012. DUOMEEN C: A 96-hour Toxicity Test with the Freshwater 

Alga (Scenedesmus subspicatus). Wildlife International, Ltd. Project No: 709A-103. Study sponsored by 

Mexel Industries, SAS C/O Mexel USA, LLC. 

97516. Casterton, P.L. (1979) Avian Dietary LC50 (Mallard Duck): Laboratory Report No. K-5096. 

(Unpublished study received Jun 16, 1980 under 38231-2; prepared by Microbiological and Biochemical 

Assay Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242696-A) 

97518. Reed, D. (1979) Laboratory Test Report: Static LC50: Rainbow Trout: Laboratory Report No. K5096. (Unpublished study received Jun 16, 1980 under 38231-2; prepared by Microbiological and 

Biochemical Assay Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242698-A) 

97519. Casterton, P.L. (1979) Fish Acute LC50 (Redear Sunfish): Laboratory Report No. K-5096. 

(Unpublished study received Jun 16, 1980 under 38231-2; prepared by Microbiological and Biochemical 

Assay Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242699-B) 

97520. Casterton, P.L. (1979) Laboratory Test Report: (Static LC50: Blue Crab): Laboratory Report No. 

K-5096. (Unpublished study received Jun 16, 1980 under 38231-2; prepared by Microbiological and 

Biochemical Assay Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242699-A) 

97521. Kresse, H.J. (1980) Daphnia magna: Acute LC50: Laboratory Report No. K-5096. (Unpublished 

study received Jun 16, 1980 under 38231-2; prepared by Microbiological and Biochemical Assay 

Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242698-B) 

97534. Casterton, P.L. (1979) Avian Acute Oral LD50: Bobwhite Quail: Laboratory Report No. K-5096. 

(Unpublished study received Jun 16, 1980 under 38231-2; prepared by Microbiological and Biochemical 

Assay Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242695-A) 

97535. Casterton, P.L. (1979) Avian Dietary LC50 (Bobwhite Quail): Laboratory Report No. K-5096. 

(Unpublished study received Jun 16, 1980 under 38231-2; prepared by Microbiological and Biochemical 

Assay Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242695-B) 

106859. Fletcher, D. (1973) Report to Nalco Chemical Company: Acute Oral Toxicity Study with 32D16 

in Bobwhite Quail: IBT No. 651-02892. Unpublished study received Apr 9, 1973 under 1706-126; 

prepared by Industrial Bio-Test Laboratories, Inc., submitted by Nalco Chemical Co., Oak Brook, IL; 

CDL: 051060-D) 

110384. Fletcher, D. (1973) Report to Nalco Chemical Company: Acute Oral Toxicity Study with 32D16 

in Mallard Ducks: IBT No. 651-02893. Unpublished study received Apr 9, 1973 under 1706-126; 

prepared by Industrial Bio-Test Laboratories, Inc., submitted by Nalco Chemical Co., Oak Brook, IL; 

CDL: 051060-C) 
Page 89 of 103

123862. Bentley, R. (1975) Acute Toxicity of Co-op Turbex to Lepomis macrochirus and Salmo 

gairdneri. (Unpublished study received Mar 5, 1975 under 1990-372; prepared by Bionomics, EG&G 

Environmental Consultants; submitted by Farmland Industries, Inc., Kansas City, MO; CDL: 110678-A) 

123863. WARF Institute, Inc. (1975) Report: WARF Institute No. 4112599. (Unpublished study received 

Mar 5, 1975 under 1990-372; submitted by Farmland Industries, Inc., Kansas City, MO; CDL: 110680-A) 

123864. WARF Institute, Inc. (1975) Report: WARF Institute No. 4112599. (Unpublished study received 

Mar 5, 1975 under 1990-372; submitted by Farmland Industries, Inc., Kansas City, MO; CDL: 110680-B) 

123866. Heitmuller, T. (1975) Acute Toxicity of Surflo-B15 to Larvae of the Eastern Oyster 

(Crassostrea virginica), Pink Shrimp (Penaeus duorarum), and Fiddler Crab (Uca pugilator). 

(Unpublished study received Jun 1, 1975 under 17664-11; prepared by Bionomics—EG&G, Inc., 

submitted by Baroid Div., N.L. Industries, Inc., Houston, TX; CDL: 165021-A) 

133265. Thompson, C.; McAllister, W. (1983) Acute Toxicity of EH&S 266 to Bluegill Sunfish: Static 

Bioassay Report 30595. (Unpublished study received Oct 25, 1983 under 10349-14; prepared by 

Analytical Biochemistry Laboratories, Inc., submitted by Visco, Div. of Nalco Chemical Co., Sugar Land, 

TX; CDL: 251787-A) 

133266. Beavers, J.; Jaber, M.; Joiner, G.; et al. (1983) A Dietary LC50 in the Mallard with EH&S 267: 

Project No. 187-103. Final Report. (Unpublished study received Oct 25, 1983 under 10349-14; prepared 

by Wildlife International, Ltd., submitted by Visco, Div. of Nalco Chemical Co., Sugar Land, TX; CDL: 

251788-A) 

134550. Fletcher, D. (1972) Report to Esso Research and Engineering Company: Acute Oral Toxicity 

Study with MRD 72-10 in Bobwhite Quail: IBT No. J1739. (Unpublished study received Jul 25, 1972 

under 8928-4; prepared by Industrial Bio-Test Laboratories, Inc., submitted by Exxon Chemical 

Americas, Houston, TX; CDL: 005650-D) 

470013023. Shapiro, R. (1984) Avian Single Dose LD50 – Bob White Quail: [Armohib B-101]: Report 

No. T-4000. Unpublished study prepared by Product Safety Labs. 14p. 

470013024. Shapiro, R. (1984) Avian Dietary LC50 Study with Bob White Quail: Armohib B-101: 

Report No. T-3995. Unpublished study prepared by Product Safety Labs. 6p. 

470013025. Shapiro, R. (1984) Avian Dietary LC50 Study with Mallard Ducks: Armohib B-101: Report 

No. T-3998. Unpublished study prepared by Product Safety Labs. 11p. 

 
Page 90 of 103

Whole Effluent Toxicity Testing

Calvert Cliffs Nuclear Power Plant (CCNPP) Whole Effluent Toxicity Testing

 Mexel was applied to CCNPP, Lusby, Maryland, cooling water during a trial by the 

facility to examine the effectiveness of the product. During this Mexel trial the Maryland 

Department of Environment required whole effluent toxicity testing with two estuarine species, 

Inland silverside (Menidia beryllina) and mysid (Americamysis bahia) (Richardson, 2011 in 

MRID 49208816). Results of the short-term chronic whole effluent toxicity tests of CCNPP 

cooling water effluent were submitted by the registrant to help characterize the toxicity and risk 

in cooling water systems of Mexel (MRID 49208816). 

 CCNPP has two generator units which share the same cooling water intake structure and 

outfall. CCNPP has a once through cooling system with a design flow of 1.2 million gallons per 

minute per generator unit (total of 2.4 million gallons per minute or 3460 million gallons per 

day) (U.S.NRC 1999). Bay water enters an intake channel, and transits through the plant in 

approximately 4 minutes (U.S.NRC 1999). Outfall 01 is offshore in 3 meters (10 feet) of water 

and the cooling water effluent is discharged at high velocity (2.7 meters per sec) which results in 

rapid mixing; the specific effluent sampling location within Outfall 01 area was not described. 

 The short-term chronic toxicity of Calvert Cliffs Nuclear Power Plant (CCNPP), Lusby, 

Maryland, cooling water treated with Mexel 432 and discharged at Outfall 01 in May, July, and 

September 2011 to Inland silverside (Menidia beryllina) was studied under effluent static 

renewal conditions. Three studies, one in May, July and September were conducted using 

juvenile Inland silverside, 9-10 days old. Four studies, one in May, June, July, and September 

were conducted using 7-8 day old mysids. In each study organisms were exposed to 100, 50, 25, 

12.5, and 6.25% effluent and a laboratory dilution water control for seven days. For Inland 

silverside and mysids the test systems were maintained at 25 + 1o

C and 26 + 1oC, respectively, 

and a salinity of 20 + 0.5 ppt. The Mexel dosing regime of the cooling water system was not 

reported for June or July. The cooling water dosing regimes provided for May and September 

differed. In May cooling water at the facility was not dosed with Mexel on the day effluent was 

collected for use in preparing test solutions for use in the last three test days, whereas in 

September cooling water at the facility was not dosed with Mexel on the day effluent was 

collected for use in preparing test solutions for the first two test days. On days Mexel was used, 

it was applied for 30 minutes at nominal concentrations of 3.3 ppm Mexel (0.056 ppm ATMD) 

to obtain 2.5 ppm Mexel (0.042 ppm ATMD) residual in the cooling water. 

 Results of the studies are summarized in Table 30. For Inland silverside the 7-day 

NOAEC values for survival, for May, July, and September effluent were all 100% effluent and 

were 50%, 100%, and 100%, respectively, for growth (measured as mean body weight (dry)). 
Page 91 of 103

There was no mortality in 100% May, July and September effluent. Other than growth, no 

observations on other sublethal morphology or behavior were observed. The most sensitive end 

point was 

 Two of the mysid studies had higher than guideline standards for an acceptable study, 

and these results are classified as unacceptable for use in characterizing whole effluent toxicity. 

The remaining tests are classified as supplemental information. The reports provided for 

documentation are draft, not finalized documents. While the studies as presented in the drafts 

appear to be scientifically sound studies for the specific facility and its treatment regime, critical 

primary study design information was missing from the package provided which would allow the 

study results to bridge to use in other cooling water systems, and the highest allowed label 

application regime. Specifically, unknown timing between dosing of cooling water system and 

collection of effluent, the lack of dosing the cooling water system with Mexel on all effluent 

collection days which is assumed to mean no ATMD would be present in effluent, and the lack 

of dosing information for some dates (e.g., all of June, July) during the effluent collection period. 

Additionally, no analytical measurements were made on ATMD levels present in the 100% 

effluent. While such analytical information was not necessary for the purpose of the study, to 

bridge to other water cooling systems such information is critical. How a user would determine 

residual Mexel at a site is not on the label. 

Table 30: Summary of Whole Effluent Toxicity Test Results for CCNPP in 2011 during 

Mexel Treatment Trial 

Endpoint Inland Silverside Results Mysid ResultsD

MayA JulyB SeptemberC JuneB SeptemberC

48-hr LC50 >100% >100% >100% >100% >100% 

96-hr LC50 >100% >100% >100% >100% >100% 

7-day NOAEC 50% 100% 100% >100% >100% 

Most sensitive 

endpoint body weightE survival, body 

weightE

survival, body 

weightE

survival, body 

weightE

, 

fecundity 

survival, body 

weightE, 

fecundity A Cooling water at the facility was not dosed with Mexel on the day effluent was collected for use in preparing test 

solutions for the last three test days. 

B Cooling water dosing with Mexel is unknown. 

C

 Cooling water at the facility was not dosed with Mexel on the first day effluent was collected for use in preparing 

test solutions for the first two test days. 

D May and July results were classified as unacceptable because control mortality was greater than guideline 

standards for an acceptable, scientifically sound study. E For each replicate the reviewer used mean dry weight (dw) per surviving fish to evaluate growth effects whereas 

study authors used total dw divided by initial number of exposed organisms to evaluate “mean biomass”. 
Page 92 of 103

Donald C. Cook Nuclear Power Plant (DCCNPP) Whole Effluent Toxicity Testing

 Mexel was applied to DCCNPP, Bridgman, Michigan, cooling water during a trial and 

on-site research by the facility to examine the effectiveness of the product. During this Mexel 

trial whole effluent acute toxicity testing with two freshwater species, Fathead minnow 

(Pimephales promelas) and the waterflea (Daphnia magna) were conducted. Results of the acute 

whole effluent toxicity tests of DCCNPP cooling water effluent were submitted by the registrant 

to help characterize the toxicity and risk in cooling water systems of Mexel (MRID 49208816). 

A Tier I ambient water quality final acute value for DCCNPP was set by the State of Michigan as 

0.1 ppm Mexel. No chronic criteria value was identified in the documentation for this facility. 

 DCCNPP has a once through cooling system with a design flow of 1.645 million gallons 

per minute (MGM) for the condenser cooling water flow, 0.16 MGM for the essential service 

water, and 0.009 MGM for the nonessential service water system, for a total intake of 

approximately 1.67 MGM (2405 million gallons per day). The total cooling water transit time 

from intake to discharge is about ten minutes. DCCNPP has high velocity discharge diffusers 

with a 3:1 dilution credit for a mixing zone in Lake Michigan. 

 Three types of effluent samples were tested for each species: 

 A 24-h composite effluent sample where grab samples were collected once every hour 

using an automatic composite sampler and where the last sample was collected during the 

30 minute Mexel treatment; 

 An effluent grab sample from the 30 minute Mexel dosing period in the previous bullet; 

and 

 Lake water dosed with Mexel from a pilot test rig mixed with two gallons of untreated 

lake water to simulate a 3:1 dilution. 

 Dosing of Mexel during the 30 minute dosing of DCCNPP cooling water and lake water 

in the pilot test rig was at 4 ppm (0.068 ppm ATMD) which was reported to result in a 2.5 ppm 

Mexel (0.0425 ppm ATMD) residual (GLEC 2006, 2007). Sample collection for the 24-hour 

composite started the morning of November 29, 2006. Sample collection continued for 24-hours 

with the last sample collected the next day, November 30, 2006, during the 30-minute Mexel 

treatment period. Sample collection for the grab sample during the 30-minute Mexel treatment 

occurred on November 30, 2006. The cooling water from the test rig was collected August 28, 

2007. 

 The D. magna tests were conducted as static exposure tests using <24 hour old 

organisms. The fathead minnow tests were conducted as static renewal exposure tests, with 

renewal at 48 hours; however the effluent was from the same effluent sample and not a new 

effluent sample (GLEC 2006, 2007). In each study organisms were exposed to 100, 50, 25, 12.5, 
Page 93 of 103

and 6.25% effluent and a Lake Michigan dilution water control. For fathead minnows and D. 

magna the test systems were maintained at 25 + 1oC (GLEC 2006, 2007). 

 Results of the studies are summarized in Table 31. For both D. magna and the fathead 

minnow the 24-h composite effluent acute toxicity was >100% effluent and there was no 

mortality in 100% effluent. Effluent collected during the 30 minute Mexel dosing period had 

acute toxicity. It was estimated from these results that for the facility, a 3:1 dilution which is the 

edge of the credited mixing zone dilution would be sufficient to meet the Tier I final acute value 

SPDES limit. A Tier I final acute criterion of 0.1 ppm Mexel was set for the edge of the credited 

mixing zone. The cooling water treated with Mexel from the pilot rig and diluted 3:1 was 

acutely toxic to both D. magna and fathead minnow. 

Table 31: Summary of Whole Effluent Toxicity Test Results for DCCNPP in 2006 and 

2007 during Mexel Treatment Trial 

Cooling Water 

Effluent 

Sample Type 

D. magna 48-h EC50 Results Fathead minnow 96-h LC50 Results 

% 

Effluent 

Nominal 

Residual 

Mexel 

Nominal 

ATMD 

% 

Effluent 

Nominal 

Residual 

Mexel 

Nominal 

ATMD 

24-h Composite 

(11/29,30/2006) >100 >2.5 ppmA 0.0425 ppmA >100 >2.5 ppmA 0.0425 ppmA

Grab Sample 

(11/30/2006) 35.4 0.88 ppmA 0.015 ppmA 27.7 0.69 ppmA 0.012 ppmA

Pilot Rig 3:1 

(08/28/2007) 65.9 0.41 ppmB

 0.007 ppmB 66 0.41 ppmB 0.007 ppmB

A Assuming 2.5 ppm Mexel (0.0425 ppm ATMD) residual in 100% effluent. The actual ATMD in 100% effluent 

was not measured. 

B Assumes the 3:1 dilution contains 0.625 ppm Mexel residual (0.0106 ppm ATMD) which is equivalent to 2.5 ppm 

Mexel (0.0425 ppm ATMD) residual target diluted 3:1. The actual ATMD in the 3:1 dilution was not measured. 

 The tests are classified as supplemental information. While the studies appear to be 

scientifically sound for the specific facility and its treatment regime, critical information that 

would allow bridging to other cooling water systems, and the highest allowed label application 

regime. No analytical measurements were made on ATMD levels present in the 100% effluent 

and how residual is determined is not defined. While such analytical information was not 

necessary for the purpose of the study, to bridge to other water cooling systems such information 

is critical. How a user would determine residual Mexel at a site is not on the label. 

Whole Effluent Toxicity Study References  

Richardson, M. 2011. Correspondence from M. Richardson, Chief, Industrial and General 

Permits Division, Maryland Department of Environment to B. Nuse, Senior 
Page 94 of 103

Environmental Specialist, Calvert Cliffs Nuclear, Power Plant, LLC re: Use of Mexel anti 

-fouling treatment in discharge for State Discharge Permit No.: 08-DP-0187, NPDES 

Permit No.: MD0002399 (copy in MRID 49208816). 

United States Nuclear Regulatory Commission (U.S.NRC). 1999. Generic Environmental 

Impact Statement for License Renewal of Nuclear Plants: Regarding Calvert Cliffs 

Nuclear Power Plant – Final Report (NUREG-1437, Supplement 1). Division of 

Regulatory Improvement Programs, Office of Nuclear Reactor Regulation, Washington, 

D.C. October. http://www.nrc.gov/reading-rm/doccollections/nuregs/staff/sr1437/supplement1/#_1_2 

Great Lakes Environmental Center (GLEC). 2006. Acute toxicity test reports for samples 

collected from American Electric Power, Cook Nuclear Power Plant on November 29/30, 

2006 in U.S.NRC Appendix V, Special Reports 2008. 

http://pbadupws.nrc.gov/docs/ML0913/ML091340525.pdf

Great Lakes Environmental Center (GLEC). 2007. Acute toxicity test reports for samples 

collected from American Electric Power, Cook Nuclear Power Plant on August 28, 2007 

in U.S.NRC Appendix V, Special Reports 2008. 

http://pbadupws.nrc.gov/docs/ML0913/ML091340525.pdf

 
Page 95 of 103

APPENDIX D: RISK ESTIMATION METHODS

 Risk estimation integrates the results of the exposure and ecotoxicity data to evaluate the 

likelihood of adverse ecological effects. There are generally two approaches used in assessing 

risks from industrial process and water systems, a risk quotient (RQ) method and a probabilistic 

method. 

Risk Quotient (RQ) Method

 In the RQ method, estimates of exposure are divided by ecotoxicity endpoint values. 

These RQs are then compared to presumptive levels of concern (LOCs) to identify potential risk 

to nontarget organisms and the need to consider regulatory action. These LOCs are standards 

used by the EPA to indicate potential risk to non-target organisms and the need to consider 

regulatory action; the development of these LOCs is discussed in detail in the Agency’s 

Overview Document42. Types of RQs (e.g., acute versus chronic), RQ equations, and 

corresponding LOCs and risk presumptions are tabulated in Table 32.

Table 32 Risk Presumption Categories 

Risk Presumption for Terrestrial Animals RQ LOC 

Acute: Presumption of high acute risk for nontarget animals EECA/LC50 or EECB/LD50 > 0.5 

Acute Restricted Use: Presumption of acute risk for nontarget animals, 

but potentially may be mitigated through restricted use EECA/LC50 or EECB

/LD50 > 0.1 

Acute Endangered Species: Endangered species may be affected acutely EECA/LC50 or EECB/LD50 > 0.05 

Chronic Risk: Presumption of chronic risk to nontarget animals, 

endangered species may be affected chronically EECA/NOAEC > 1.0 

Risk Presumption for Aquatic Animals RQ LOC

Acute: Presumption of high acute risk for nontarget animals EECC

/LC50 or EECC/EC50 or 

EECC

/IC50

> 0.5 

Acute Restricted Use: Presumption of acute risk for nontarget animals, EECC/LC50 or EECC/EC50 or > 0.1

Acute Endangered Species: Endangered species may be affected acutely EECC

/LC50 or EECC/EC50 or C > 0.05 

Chronic Risk: Presumption of chronic risk to nontarget animals, 

endangered species may be affected chronically 

Water: EECC

/NOAEC > 1.0 

Sediment: EECD/NOAEC >1.0 

Risk Presumption for Aquatic Plants RQ LOC 

Non-Endangered Species: Presumption of high risk to all nontarget 

aquatic plants EECC

/IC50 > 1.0 

Endangered Species: Endangered plants may be affected EECC/NOAEC or EECC/IC05E > 1.0 

Risk Presumption for Terrestrial Plants RQ LOC 

Non-Endangered Species: Presumption of high risk to all nontarget 

plants EECC

/IC25 > 1.0 

Endangered Species: Presumption of high risk to all nontarget aquatic 

plants EECC

/NOAEC or EECC/IC05E > 1.0 

 

42 http://www.epa.gov/espp/consultation/ecorisk-overview.pdf 
Page 96 of 103

A Dietary exposure in parts per million (ppm) of the pesticide in/on dietary items. 

B Dietary exposure dose in mg/kg-bw/day. 

C Concentration in water in parts per million (ppm). 

D Concentration in mg/kg-sediment. 

E An IC05 can be used in lieu of an NOAEC, if one cannot be determined or if it is above the IC25. 

Probabilistic Method

 For use patterns that result in antimicrobials entering surface water by way of industrial 

wastewater treatment plants or direct discharge from the industrial site without treatment, the 

Agency relies upon estimating loadings of antimicrobials to industrial wastewater treatment 

plants and using the General Population Exposures from Industrial Releases module of E-FAST 

to estimate number of days of exceedance of concentrations of concern (COCs) for aquatic 

organisms. COCs for acute effects on non-listed aquatic vertebrates and invertebrates were 

determined by dividing LC50 (or EC50) values from acute toxicity tests on aquatic vertebrates and 

invertebrates, respectively, by 2. COCs for chronic effects for non-listed aquatic vertebrate and 

invertebrate species were based on chronic NOAEC values from tests on aquatic vertebrates and 

invertebrates, respectively. Acute COCs for listed endangered and threatened aquatic vertebrates 

and invertebrates were determined by dividing acute LC50 (or EC50) values from acute toxicity 

tests on aquatic vertebrates and invertebrates, respectively, by 20. COCs for nonlisted aquatic 

vascular plants and algae are based on IC50 values. COCs for endangered algae and aquatic 

vascular plants are based on NOAEC values. 

 Based on probabilistic modeling results, if the acute COC (one-half of theLC50 or EC50) 

determined for any key aquatic receptor group is exceeded for one day or more based on results 

from the high-end scenario (i.e., the 10th percentile of the ratio of 7Q10 (i.e., lowest 7 

consecutive-day stream flow over a 10-year period) stream flows to plant flows), then potential 

acute risks to such receptor groups are indicated. In addition, if the endangered COC (onetwentieth of the LC50 or EC50 ) determined for any key aquatic receptor group is exceeded for 

one day or more based on results from the high-end scenario, then potential acute risks to 

endangered aquatic organisms in such receptor groups are indicated. Furthermore, if the chronic 

COC (NOAEC or NOAEL) for any key aquatic receptor group is exceeded for 20 days or more 

based on results from the high-end scenario, then potential chronic risks for such receptor groups 

are indicated. 

 
Page 97 of 103

APPENDIX E: ECOLOGICAL EXPOSURE MODELING METHODOLOGY

Methodology for Estimating Water Column Exposure to Aquatic Organisms

from Release of ATMD from  Recirculating Cooling Towers

 The General Population and Ecological Exposure from Industrial Releases module of EFAST (Exposure and Fate Assessment Screening Tool) was used to estimate potential risks from 

exposure of aquatic organisms to ATMD downstream of recirculating cooling towers. Key input 

parameters required to run this module of E-FAST include: 

 Environmental release of ATMD to surface water (kg/site/day); 

 Concentrations of concern (COC) for aquatic organisms (ug/L); 

 Standard Industrial Classification (SIC) code(s) selected to represent recirculating 

cooling tower facilities; 

 Wastewater treatment removal of ATMD (percent); 

 Annual number of days of release to surface water (days per year); and 

 Selection of high-end or average case scenario. 

 A discussion of the basis of high-end and average case scenario results is included at the 

end of this Appendix. The approach used to estimate aquatic exposures to ATMD from release 

of blowdown water from recirculating cooling towers can be described in four steps: 

 Step 1: Estimate environmental release to surface water from recirculating cooling 

tower blowdown water from recirculating cooling tower blowdown water 

(kg/site/day); 

 Step 2: Determine percent removal during wastewater treatment; 

 Step 3: Derive concentrations of concern (COC) for aquatic organisms from LC50

and NOAEC values; and 

 Step 4: Estimate aquatic exposures from releases of recirculating cooling tower 

blowdown water to surface water using the general population exposures from 

industrial releases module of E-FAST. 

STEP 1: Estimate Environmental Release to Surface Water from Recirculating Cooling Tower

Blowdown Water (B) in kilograms per site per day

 A generic scenario developed by OPPT/CEB (Office of Pollution Prevention and 

Toxics/Chemical Engineering Branch) for recirculating cooling towers (USEPA, undated) was 

used to estimate daily releases to surface water of ATMD in blowdown water in kilograms per 

site per day. 
Page 98 of 103

 The following equation is used to estimate releases of antimicrobial pesticide to surface 

water from blowdown: 

B = (0.6%) (XR) (R) (5760 x 10-06 min-kg/day-gal) 

where: 

B = release of antimicrobial pesticide via blowdown water to surface water (kg/site/day); 

 XR = concentration of antimicrobial pesticide in recirculating water (ppm); and 

 R = recirculation rate of cooling water (gallons per minute). 

 The conversion factor, 5760 x 10-06 min-kg/day-gal is derived from: 

(1440 min/day) (4 kg/gal) (10-06 ppm) in which the blowdown water is assumed to have a 

specific gravity of 1.0, thus 1 liter weighs 1 kilogram, and the conversion of 3.78 liters per gallon 

is expressed in kilograms per gallon and rounded up to the nearest significant figure. The value, 

0.6% is the percentage of cooling tower water that is assumed to be released to surface water via 

blowdown. 

 The following input values were used in this calculation: 

 XR: concentration of ATMD in recirculating cooling tower water – 0.5 to 40 ppm 

ATMD acid equivalents (derived from information on the label for “Antimicrobial 

ATMD 15%” (EPA Reg. No. 464-619) based on the range of product application 

rates (0.5 to 41 fluid ounces per 1000 gallons of water) adjusted for product density 

(8.5 pounds per gallon) and expressed as ATMD acid equivalents (12.8%) 

 R:recirculation rate of cooling water– 2000 gallons per minute for a moderate-size 

cooling tower (default value based on standard scenario developed by OPPT/CEB)) 

and 100,000 gallons per minute for a large-size cooling tower (default value based on 

standard scenario developed by OPPT/CEB). 

 The table that follows presents values of environmental releases of ATMD modeled for 

large-size and moderate-size cooling towers according to product application rate, product 

density, and ATMD concentration in acid equivalents. 

STEP 2: Determine Percent Removal During Wastewater Treatment

 Data from an activated sludge sorption isotherm test (OCSPP Guideline 835.1110) that 

were submitted to the Agency for review indicate that based on 4 to 6 hours of treatment in an 

activated sludge basin from 71-92 percent of ATMD is removed via its sorption to activated 

sludge (Schaefer, E and A Ponizovsky. 2012 (MRID 490402051); see references in Appendix A 

for full citation). For the purpose of this exposure and risk assessment, estimates were provided 

based on 4 hours of treatment with 71 percent removal via sorption to activated sludge and based 

on 6 hours of treatment with 92 percent removal via sorption to activated sludge. 
Page 99 of 103

 There is no information on the product label to indicate that blowdown water must be 

treated prior to discharge to surface water. Consequently, exposures and risks to aquatic 

organisms were also estimated assuming that blowdown water could be discharged directly to 

surface water without treatment. In this case, it was assumed that there would be no removal of 

ATMD from blowdown water prior to its discharge to surface water. 

STEP 3: Estimate Concentrations of Concern (COC) for Aquatic Organisms

 The results of the DtD module are expressed as number of days of exceedance of COCs 

for aquatic organisms. The Agency uses the most sensitive ecotoxicology endpoints for 

surrogate species to assess risk to each aquatic receptor group, such as freshwater fish, 

freshwater invertebrate, sediment-dwelling invertebrate, and aquatic plants. COCs for acute 

effects were determined by dividing LC50 values from acute toxicity tests on aquatic vertebrates 

and invertebrates by 2. COCs for chronic effects for non-listed species were based on No 

Observed Adverse Effects Concentration (NOAEC) values from tests on aquatic vertebrates and 

invertebrates. COCs for listed endangered and threatened aquatic organisms were determined by 

dividing LC50 values from acute toxicity tests on aquatic vertebrates and invertebrates by 20. 

Acute COCs for aquatic vascular plants and algae are based on EC50 values. COCs for 

endangered algae and aquatic vascular plants are based on NOAEC values. 

STEP 4: Estimate General Population and Ecological Exposure from Industrial Releases

 E-FAST, version 2.0, was used to determine the magnitude and frequency of exposure of 

aquatic organisms from releases of ATMD via blowdown water from recirculating cooling 

towers. For detailed information on the features, data, and methods on which the models in EFAST, version 2.0, are based, refer to the latest version of the Documentation Manual for EFAST, version 2.0 (USEPA 2007). This discussion is limited to summarizing the steps required 

to estimate exposure of aquatic organisms to blowdown water from industrial use of ATMD in 

recirculating cooling towers using the General Population and Ecological Exposure from 

Industrial Releases module of E-FAST with the PDM (probabilistic dilution model) option. The 

user is guided through a series of menus or pages that provide prompts indicating where the user 

should input data. Key input parameters needed to run this module and option include: 

 Environmental release to surface water in kg/site/day (estimated from Step 1); 

 Percent removal of ATMD during wastewater treatment (from Step 2); and 

 Concentrations of Concern (COC) for aquatic organisms (estimated from Step 3). 

 One of the first screens that appears when running the General Population and Ecological 

Exposure from Industrial Releases module of E-FAST is the physical/chemical and fate inputs 

screen; Upon accessing this screen, the user must enter the following information: 

 Chemical identification (e.g., CAS number); 
Page 100 of 103

 Chemical name or abbreviation; 

 Bioconcentration factor (measured or estimated) (used to estimate human exposure from 

ingestion of fish); 

 Percent wastewater treatment removal (measured or estimated); 

 Percent adsorption to wastewater treatment sludge (measured or estimated); and 

 Percent drinking water treatment removal (in the absence of data, assume no removal). 

 The user must also select the appropriate models for estimating exposure to aquatic 

organisms. (In this instance, the appropriate model to use is the general population and 

ecological exposure from industrial releases to surface water model with the option to also run 

the probabilistic dilution model.) Next, the user accesses the “Release Information Page”. This 

page consists of three sub-pages including: 

 general release information; 

 select a facility; and 

 select an SIC code. 

 The “select a facility” subpage, which accesses a database of site-specific information for 

manufacturing facilities, is not applicable for estimating exposures from processing and 

industrial use. To estimate exposures to aquatic organisms from surface water releases from 

processing or industrial use, the user must provide input values for the “general release 

information” subpage and the “select an SIC code” subpage. On the general releases 

information subpage, the user must input the following: 

 type (media) of release (i.e., surface water, landfill, and/or ambient air); in this case, 

the user would select “surface water”. 

 amount of release in kg/site/day, based on the results from CEB’s generic scenario 

(from Step 1 of this appendix) ; 

 days per year of release, based on results from CEB’s generic scenario; the default 

value for the recirculating cooling towers scenario is 360. 

 Upon being present with a choice of selecting “SIC code analysis” or “facility 

analysis”, select SIC code analysis. A menu of SIC code descriptions will appear on 

the screen and the user will be prompted to select one; in this instance, the appropriate 

SIC code description would be “Steam Electric Power Plants”. 

 Input the number of cooling tower sites; since there is no production volume 

information available for ATMD used in recirculating cooling towers that can be used 

to derive this input, no value is entered. 

 In the box, “enter release activity”, the user has the option to enter a description of the 

release; in this case, an apt description might be “indirect release of cooling tower 

blowdown”. 

 Place a check in the box, “include PDM run”. 

 Enter three values for concentrations of concern. 
Page 101 of 103

 Select results for high end or average exposure. 

 Finally, check the box, “Release activities completed? Continue to Exposure Factors 

page.” Upon checking this box, the Exposure Factors page will appear. 

 The information in the exposure factors page is not used to estimate exposures to aquatic 

organisms, but is used to quantify human exposures from ingestion of drinking water and fish. 

This page includes default values for body weight, exposure duration, averaging time, and acute 

and chronic drinking water and fish ingestion rates. These values are automatically selected 

unless the user changes them. 

Methodology for Estimating Exposure to Aquatic Organisms from Release of

ATMD from  Once­through cooling systems

 With the exception of Step 1 described in the approach used to estimate environmental 

releases of active ingredient to surface water from recirculating cooling tower s, the methodology 

used for estimating exposure to aquatic organisms from release of ATMD from once-through 

cooling systems is the same as that used for estimating exposure to aquatic organisms from 

recirculating cooling towers. Whereas the release of active ingredient to surface water from 

recirculating cooling towers is limited to cooling tower blowdown water, the release of active 

ingredient to surface water from once-through cooling systems is based on the intake flow. 

Consequently, Step 1 of the approach for estimating environmental releases to surface water 

from recirculating cooling tower blowdown water (B) in kilograms per site per day would be 

modified as follows: 

 Convert once-through cooling tower throughput in million gallons per day (MGD) to 

 liters per day 

 Convert maintenance concentration of ai in ppm to ug/L 

 Use throughput in liters per day and concentration of ai in ug/L to derive kilograms of ai 

 per site per day 

For example, to convert 2 MGD of throughput with 2.5 ppm of product at 1.7% active ingredient 

to kilograms per site per day of active ingredient released to surface water: 

 Convert 2 MGD to liters per day. 

2,000,000 gal/day x 3.785 liters/gallon = 7,570,000 liters/day 

 Convert ppm ai to ug/L. 

2.5 mg/L product x 0.017 active ingredient/product x 1000 ug/mg = 42.5 ug/liter 
Page 102 of 103

 Use liters of throughput per day and concentration of ai in ug/liter to determine 

kg/site/day 

42.5 ug/L x 7,570,000 liters/day x 1 kg / 109

 ug = 0.3217 kg/site/day 

Description of High­End Versus Average Case Scenario

 The General Population and Ecological Exposure from Industrial Releases module of EFAST uses environmental releases estimated in Step 1 of this Appendix, stream dilution factors 

(i.e., the ratio of stream flow to industrial wastewater treatment plant flows), and wastewater 

treatment removal efficiency to provide both high-end and median time-averaged surface water 

concentrations of a chemical substance immediately downstream of a discharge point. Stream 

flows are not single point estimates since streams have a highly variable seasonal flow pattern. 

PDM uses probability distributions as inputs and calculates the resulting probability distribution 

of the stream concentration. 

 To determine stream dilution factors for industrial uses of chemical substances such as 

ATMD used in recirculating cooling towers, a representative SIC code must be selected. The 

model will develop a distribution of stream dilution factors based on the ratio of stream flows to 

plant flows for facilities that belong to a specified SIC code. The distribution of stream flow 

values used is those immediately downstream of the facilities that belong to a specified SIC 

code. For this risk assessment, stream dilution factors (SDFs) for recirculating and once-through 

cooling systems were based on the ratio of receiving stream flows to facility effluent flows for 

those facilities included in the steam electric power plants SIC code (SIC 4911). For the highend scenario, results of the number of days per year that COCs are exceeded are based on the 

upper 10th percentile of SDFs. For the average case scenario, results of the number of days per 

year that COCs are exceeded are based on the 50th percentile of SDFs. For the upper 10th

percentile SDFs, or high-end scenario, the stream flow to plant flow ratio is relatively low since 

plant flows can contribute considerable volume to the flow of the stream and resulting surface 

water concentrations can be relatively high. For the 50th%ile SDF, the stream flow to plant flow 

ratio is more typical. 

Methodology for Estimating Sediment Exposure to Benthic Aquatic Organisms

from Release of ATMD from Once­Through and Recirculating Cooling Towers

 Two approaches were used to estimate sediment concentrations to which benthic aquatic 

organisms would be exposed. Inputs used to estimate freshwater sediment concentrations 

included: 
Page 103 of 103

 Estimated surface water concentrations based on results from the Industrial Releases 

module of E-FAST; 

 Average .Kf value from a study on sorption of formulated Duomeen C to five soils 

(Schaefer, EC. and AA Ponizovsky. 2012b. MRID 490040206; (See reference cited 

in Appendix A for complete citation)) 

Inputs used to estimate estuarine/marine sediment concentrations included: 

 Effluent concentration of ATMD at the end-of-pipe (42.5 ug/L) 

 Average Kf value from MRID 490040206 as referenced above. 

The following equation is used to estimate sediment concentrations: 

 Cs = Kf x Cw x 1 mg/1000 ug 

Where 

Cs is the concentration of ATMD in the sediment (mg/kg sediment), 

Kf is the average leaching adsorption/desorption value (L/kg) (See Table 21), and 

Cw is the concentration is surface water or end-of-pipe concentration of ATMD (i.e., 42.5 ug/L). 

APPENDIX E – REFERENCES

Ackerman, D, F Ghillebaert, and MW Glass. 2013. Duomeen C Water Concentration Modeling 

for Cooling Water Towers and Once-Through Industrial Cooling Water Systems. MRID 

49040220.