**_,,~EO** 

### Sl..q r:,**v~ ~\9**  

# j 

# 8 =u UNITED STATES ENVIRONMENTAL PROTECTION AGENCY S**~** 

# "ffi WASHINGTON D.C., 20460 )J <!) 0**~**

### ~-**~ ~.**  

## .c.P OFFICE OF CHEMICAL SAFETY .,)':. r.' AND POLLUTION PREVENTION 

### All. PRQ\CC.v



### MEMORANDUM SUBJECT: December 19, 2012

Amended Product Chemistry, Environmental Fate, and Ecological Effects Scopif g Document in Support of Registration Review of Poly(liexamethylene

-biguanide) hydrochloride 

# I PC Code: 111801 DP Barcode: 407780 ;Deci&ion No.: 459677 Registration Nos.: None Petitipn No(s).: NA Regulatory Action: Ecological Environmental Scoping Document for Registration Review Risk Assessment Type: Single chemical Case No.: 3122 TXRNo.:NA CAS No.: 32289

-58-0/27083-27-8 MRID Nos.: See Tables 3 & 4; 40CFR: None Pg. nos. 9, 10, 12-16 f.;/ ( Srini 1 as Gowda, M
. S. Microbiologist

### ~**(,t/~** Donna Randall, M.S., Senior Effects Scientist 

### FROM:

THRU:

TO: Najm Shamim, Ph.D., Chemist

### M!--u:~
r ti icrobials Division (7510P)
. 

### r Steve Weiss, Chief

# ~**!Y~** Risk " I ssessment and Science Support Branch (RASSB) Antimicrobials Division (751 OP) 

### ;r'ike

# endelsohn, Branch Chief t.ance Wormell, Team Leader Rebecca von dem Hagen, Chemical Review Manager Regulatory Management Branch II Antimicrobials Division (7510P)

Page 1 of 25

### Executive Summary Poly(hexamethylene) biguanide hydrochloride**(PHMB·HC~),** case 3122, is a biguanide cationic polymer used as a broad spectrum antimicrobial (effective l agaimst many types of microbial organisms

- aerobic and anaerobic bacteria, yeasts, fung·, and molds). PHMB·HCl exists as a polydisperse mixture which means it consists of a mixture of differing polymer lengths or sizes, referred to as PHMB. PHMB·HCl is registered fo t use as a fungicide, algicide, and sanitizer for use with swimming pools, spas and hot tubs; a ma terials preservative in architectural and industrial coatings, textiles and cellulosic material , glues and adhesives, leather and fresh animals skins and hides; a microbicide/microbiostat in intlustrial processes and water systems including cooling towers; and as a hard surface (food and 

# t l on-food contact surfaces) disinfectant/sanitizer in a variety of residential and public access p mises, commercial, institutional, industrial premises and equipment, medical and agric ltural premises and equipment, and food handling storage establishments and equipmet t. PHMB-HCl was first registered in the United States in 1982 as an 1 ctive ingredient. Currently, there are twelve companies with a total of 25 active product**registr tions**  containing PHMB. Two of the products are registered technical products with**PHMB·~Cl** active ingredient declarations of 20% and 96.3%. The remaining 23 products are registered end

-use products with PHMB·HCl active ingredient declarations ranging from 0.08 to 96. B%
. End-use products are I formulated as flowable soluble concentrates (0.08 to 20% PHMB·HCl), ready

-to
-use solutions (0.1% to 20% PHMB·HCl), a solid soluble concentrate (96.3% PH¥B ·HC1), and wet wipes (contains solution of 0.1% or 0.5% PHMB·HCl). Clarification on the character of the PHMB polymer dispersion of each of the technical products (range and distribu ion of polymer chain lengths and average polymer size) and their variability is needed. A Reregistration Eligibility Decision (RED) was issued by JEPA for PHMB·HCl in September 2004. At the time of the RED, PHMB hazards were chd racterized as part of the assessment but no quantitative risk assessment was performed. Astart of the registration review process, a risk assessment for those PHMB·HCl use pattern resulting in discharge of PHMB to water will be conducted such as industrial processes and ater systems uses such as cooling towers, paper mill process water, and consumer, institutipnal, commercial product uses resulting in down-the-drain disposal or discharge to receiving**ate~s.** While there is some understanding of the likely environmenta l fate of PHMB based on its physical and chemical properties, there is very little**informat on**  that can be applied quantitatively. The likely primary dissipation pathway for PHMB is sorption and reaction with humic acid, suspended solids, and sediment. To conduct the registration review assessment for residential, commercial, institutional consumer products (e.g., pools , spas, hot tubs, detergent) and industrial processes and water systems, and material pres ervative wastes that may be discharged to waste water treatment plants (WtTPs), the Agency anticipates needing an activated sludge sorption/desorption study and an activated sludge respiration inhibition test with the technical grade active ingredient products. A number of ecological effects data are required to allow conduct of a risk assessment to the aquatic environment both freshwater and estuar ine/marine systems

### (freshw**ter** and estuarine /marine fish and invertebrate acute testing, freshwater and estuarine fish early life stage testing and invertebrate life cycle testing, aquatic vascular and nonvascular toxicity data, and chronic whole sediment toxicity testing). Avian acute oral testing is also required. Page 2 of25

### Introduction PHMB·HCl was first registered in the United States in 1982 as an active ingredient for use in manufacturing swimming pool sanitizers and disinfectants for use in commercial, industrial, and residential settings and to formulate sanitizers and disinfectants for use in food handling/storage establishments, premises and equipment, including food contact surfaces in public eating places, dairy processing equipment, and food processing equipment and utensils. Currently, there are 25 prod cts containing PHMB·HCl (two technical products and 23 end

-use products) for use as algaecides, bacteriocides/ bacteriostats, fungicides/fungistats, microbicides/microbiostats, Jlimicide, disinfectants, and sanitizers. PHMB is registered for use as a fungicide, algicide, and**~anitizer** in swimming pools; a materials preservative in architectural and industrial cchatings, textiles and cellulosic material, glues, leather, and fresh animals skins and hides; a mtcrobicide/microbiostat in industrial processes and water systems including cooling tower$; anf as a hard surface (food and non-food contact surfaces) disinfectant/sanitizer in a**var ety**  of residential and public access premises, and commercial, institutional, industrial, medical, and agricultural premises and equipment, and food handling storage establishments and e ' uipment. A detailed list of use patterns and use sites of PHMB are listed below. 

### Use Patterns and Use Sites I 

### Swimming Pools 1 Swimming pools, spa and hot tub water systems.
premises. 

### Food handling storage establishments and equipment Hard,**non po** **ous** surfaces in restaurants/eating establishments such as kitchen countertops, High chairs, refrigerators, and microwave ovens. 

### Commercial, Institu l onal and Industrial Premises and Equipment Hard, non-pOFous surfaces such as garbage cans, walls, floors, and stainless steel surfaces. 

### Medical premises and equipment Hard,**non-po ous**  surfaces in hospitals, nursing homes , animal laboratories and veterinary offces. 

### Residential and Public Access Premises Hard, non-porous surfaces such as tables, countertops, stovetops, sinks, cabinets , refrigerators, microwave ovens, high chairs, tubs , floors, glazed tiles, urinals, diaper pails ar d other bathroom surfaces, garbage cans, walls, floors, stainless steel surfaces kennel runs , pet areas, sealed stones, glazed ceramics, playground equipment, and picnic tables. 

### Industrial processes and water systems Page 3 of25Drilling muds and packer fluids in addition to workover fluids
. Oil field injection water and tunnel pasteurization water. Cooling towers . Materials Preservatives For use in the preservation of electrocoat resins in addition to aqueous industrial chemicals such as reagents, oil

-in

-water emulsions, water
-in

-oil emulsions, cellulose solutions, silicone emulsions and silicone dispersions, aqueous mineral slurries such as calcium carbonate and titanium dio:xlide as well as polymer lattices such as polyvinyl acetate and polyvinyl alcohol. For the preservation of textiles and cellulosic materi ls such as carpet, curtains, mops, dishcloths, wipes, sponges, tissues and non-i od**ntact** paper products. For the preservation of leather, fresh animal hides d skins prior to or during processmg. For the control of microorganisms in aqueous adhesives such as animal glues, latex adhesives and other synthetic and protein based glues
. 

### I A Reregistration Eligibility Decision (RED) was issued by PA for PHMB in September 2004 1 • At the time of the RED, PHMB hazards were characterized as part of the assessment but no quantitative risk assessment was performed. To regulate the in stri& l microbiocide uses and associated risks to the aquatic environment, the Agency required th t

### la**els** for PHMB products require discharges to aquatic environments comply with a National Pollutant Discharge Elimination System (NPDES) permit. The only use pattern identifi1d as likely to result in significant outdoor exposure was the oil recovery use; however,**la ellanguage**  prohibiting use over or near marine/estuarine (e.g., offshore) oil fields was used to**ddress** these hazards. As part of the registration review process, risk assessments for those PHMB use patterns resulting in discharge of PHMB and its major degradates of concern to water w·ll be conducted such as applications to cooling towers; paper mill process water; consumer**inst tutional,**  commercial product uses resulting in down

-the

-drain disposal or discharge to re 1

1 ceiving waters; and oil well process and development uses. Mode of Act i on

# ~ PHMB is a

## me~brane active agent. PHMB interacts with

## e surface of cell membranes. As PHMB binds to the membrane, it drags acidic phospholids to thf location

- reorganizing the membrane, creating an acidic lipid domain

- surface membrane acq vity. l This aggregation of acidic phospholids leads to increased fluidity and permeability of tlie**mbrane** resulting in the release of lipopolysaccharides from the outer membrane, potassiu 

### Iion efflux, and eventual organism's death.

1 http://www.epa.gov/oppsrrd 1/REDs/phmb red.pdf Page 4 of25

### A. Product Chemistry Summary of PHMB PHMB exists as a polydisperse mixture which means it consists of a mixture of polymer chains of different lengths on sizes, and mass (a monodisperse polymer would consist of polymers of the same size and mass). A single monomer unit is the hexamethylene biguanide unit (see the molecular structure in Table 1). Information submitted on the characterization of one of the technical products identifies chain lengths ranging from n 

## = 1 to 40 mers. The average molecular weight for the samples tested range from n 

## = 10 to 13 mers which indicates that the distribution of polyJer chain lengths in registered products varies
. Additionally, the PHMB polymer chain does not have a single identical end group, it may end in an amine (

- NHz) or a cyano (

- CN) group being the terminal (end) group(s) based on the manufacturing process . A summary of the prbduct chemistry data for the monomer of PHMB, designated PHMB·HCl because it includes the hydrochloric acid component (HCl), is provided in Table 2. There has been some confusion over the range and distribution of mer length present in the antimicrobial PHMB use**pn~ducts.** The 2004 RED provides a potential chain length for PHMB polymer dispersion of 1 to 4? mers with an average of 12. In

-house information gives differing characteristics: one study implies mer length of 1 to 12 mers with average of 4
.5 to 5.5 mers, another indicates 1 to 40 mets with average of 12 mers . Literature findings for PHMB pesticidal products indicate polymer chain lengths of 1 to 40 mers (e.g
. , de Paula et al. 2011). The exact length, and number of mers present in the technical grade products (i
. e., 20% versus 96
. 3%, versus historic in

-house datalon 20%) is needed to help in understanding the fate of the dispersion contained in PHMB products
. Without this information it is unknown how reflective or how bridgeable informatibn on the fate or toxicity of the PHMB polymer dispersion in the current 96
. 3% and 20% technical products are to historic fate and effects data conducted with 20% polymer dispersions. Table 1. Chemical ldenti 

### y PHMBHCI Chemical Name**oly(ifninoimidocarbonyliminoimidocarbonyliminohexamethylene)** hydrochloride P oly(iJTiinocarbonimidoyliminocarbonimidoylimino-1 ,6

-hexanediyl) hydrochloride Common Name**Poly( examethy** lenebiguanide) hydrochloride Polyhexamethylene biguanide hydrochloride Polyhexanide Synonyms Polih xanide HCI Polyh,examethylene biguanide HCl Trade Names Vantocil P; Baquacil; Baquacil SB; Cosmoquil CQ; PHMB; VantocillB Molecular Weight 2 19
. 718 g/mol (monomer unit and includes HCl) PC Code 11180 11 CAS No. Open literature search put the two CAS#s together: 27083

-27

- 8 and 32289-58-0, but no information is provided on the second one. ' Molecular Formula (Cs H / 7 Ns)n
. xHCI 2

2 

### I

. Note: The molecular weight of**P~** can vary as the value of ' n' (the number of mers) can be a little as I and as many as 12. The average for Baquacil is reported as 4
.5 to 6.5. Thus the molecular weight (MW) reported in this document is with n= 1, one mole fhydrochloric acid (HCl) is included in the MW
. This is the moiety registered with the Agency
. Page 5 of25

### PHMBHCI M o lec ular S tructure: 

# [ 

# l NH NH I 

## II II NH - c - NH - c - NH - ( CH 2) 6 

# I

• X HCl
l Table 2. Product Chemistry Data Summary of PHMB·HCI I Guideline Physical and PHMB·HCl PHMB·HCl No. Chemical Properties 96.3% Solid 20% weight to volume (w/v) (Technical) Aqueous Solution (Technical) 830.1 55 0 Product identity and Refer to Table 1. Re fer to 7'able 1. composition 830.1800 Enforcement Mass spectroscopy (MS) Infra-Red Spectra. analytical methods UltraViolet Spectrophotometry**N~Spectra.** Infra-Red Spectra Capillary GC Nuclear Magnetic Resonance (NMR) High Performance Liquid Spectra Chlomatography (HPLC) Gas chromatography (GC) 8 3 0.63 02 Color Off white to pale yellow solid Colorless to yellowish 830
. 6303 Physical State Lumpy solid Liquid 830.6304 Odor None No 1discernible odor 830
. 6313 Stability to sunlight, Stable at 3 months Staple under normal condition
. normal and elevated Stable at 54 ± 2 degrees Celsius (0 C) for Sta p le for 14 days at 54 ± 2°C. temperature , two weeks
.

# ~:r' ange . metals/metal ions Onset of decomposition: 205 to 210 

### oc minum, copper, iron, and zinc- no

.ct. 830 .7000 pH 4.36 for a 1% solution at 21.7 °C**5~** solution(= 1% active agent): 5.7 830. 7050 UVNi sible PHMB absorption spectra maximum PH**~** absorption spectra maximum Absorption was not found in visible wavelength.**wa ~**  not fo und in visible wavelength. 830.7100 Viscosity Not a Liquid _ 3 1 ,2.10 Pascal·second (Pa·s) 830
.7200 Melting point 7 8
.9

- 136
. 3°C


### ------ Decomposition begins at 205

- 21 0 °C. Melting point around 100 ° C 830.7220 Boiling point B oiling point is not applic able since this l02 °C product is a solid and not a liqu id. 830
.7300 Density 1.26 gl cm3 at 25°C Relative density 1
.044 at 20°C 830 .7 370 Dissociation Constant pKa=4.19 at 25 °C 1.2 ± 0
.5 X 10

- 1 at 25 °C 830 .7550 Partition coefficient Log Pow = -2
. 62 Log Pow= -2 .62 (n-octanoVwater) 830.7840 Solubility in water 39
.0 to 43.4% w /v 23.5°C


### --- --- 830.7860 Solubility in organic Methanol : 41% w/w ±1% at 25 ±1 

### o c
------ solvents Ethanol : 0.5% w/w ± 0.08 % at 25± I 

### o c 

# I Acetone: 2.7 ppm at 22°C Dichloromethane: 0
.2 ppm at 22°C Ethyl Acetate:= 0.1 _pp

_ m at 22°C 

### Page 6 of25Guideline Physical and PHMB·HCI PHMB·HCI No. Chemical Properties 96.3% Solid 20% weight to volum e (w/v) (Technical) Aqueous Solution (Technical) 

# ' Toluene : 0.2 ppm at 22°C n-hexane : 0.1 ppm at 22°C Acetonitrile: 0.8 ppm at 22°C 830.7950 V apor pressure 1.5 X 10· 9 mmHg at 25°C


### -- ---- Henrys Law Constant 1.05£-015 atm-m3/mo le (Calculated)

---- - - at 25 

## o c N/A =not applicable; TGAI = tecj mcal grade active mgredient; w/w = weight m weight 

### B. Environmental ate Summary PHMB ·HCl was orig nally registered for conventional uses and regis trants had submitted some fate studies that were not identified in the 2004 RED. These studies are included in this document. However, these studies were not conducted according to the Agency's environmental fate test guidelines as they

### ere generated prior to 1984 and the Agency ' s test guidelines were generated after that date. In flddition an open literature search was conducted and data results from some relevant studies are also included in this summary. PHMB is hydrolytically and photolytically stable under abiotic conditions and is stable under both aerobic and anaef obic conditions
. When applied to soil PHMB is not expected to migrate into soil to any appreciable distance. This lack of mobility is most likely due to its positive charges. It is desorqed on the soil surface and hence is not mobile in soils. Because it is not mobile in various soils,**HMB** discharged into aquatic systems would be expected to be associated with sediments arid not the water column. In a WWTP, PHMB would be expected to associate primarily with the t iosolids. PHMB is not expected to bioaccumulate in biota. As the technical**gra~** products contain a mixture of polymers (e

. g ., monomers, dimers , trimers, tetramers, and = 5 to 40) , and the distribution of the polymer length or size, as well as end groups being dif f

erent (z.e., -NH2 and/or -CN), the fate chemistry is expected to potentially differ between the 20%**PH B**  (historic test substance), 20% and 96.3 % PHMB technicals. Essentially all of the fate stutlies have been conducted with Vantocil IB or Vantocil P which are 20% products containing lo er molecular weight polymer chains of PHMB (characterization information of test substancJ is average of n=4.5 to 5
.5 mers)
. The 96
. 3% PHMB is characterized as having a di tribution containing higher molecular weight chain polymers with an average of 12 mers. The rollowing discussion on the fate of PHMB is based on studies conducted using a 20% technical grade product with the lower molecular weight (average n=4.5 to 5.5 mers) polymer disper ion. Information bridging the fate characteristics of these distributions with chain length has not been provided, so there is uncertainty in the fate characteristics of the longer b hain polymers in environmental media
.

Page 7 of25

### Abiotic Fate It has a low vapor pressure (- 10-9 mm Hg) and the Henry law constant is very low so it does not have a tendency to volatilize from surface water. PHMB i readily soluble in water (39.0 to 43.4% w/v 23.5°C) but shows little solubility in hydrocarb bns. Critical micelle concentration (CMC), i.e. point where micelles form, in water has

### een reported in literature for an unknown PHMB product to range from 1 x 10- 3 to 5 X 10-2 mole per liter (de Paula et al., 2011). Hydrolysis PHMB is hydrolytically stable under abiotic conditions and nd j goes < 10% degradation at pHs 5, 7, and 9 (MRID 43622301). Recently the Food and Drug Administration (FDA) publish d a hydrolysis study (Lucas, 2012) on PHMB which is registered with FDA for germicidal uses. 1 No hydrolysis of PHMB in water occurred. Even after 60 days in a phosphate buffered saline solution 90% of PHMB was still present (only 10% degraded). Under acidic conditions (HCl c ncentration at 1 Molar (M) 3 or 0.01 M conditions) PHMB did hydrolyze immediately, but in a 1 M 3 olution of sodium hydroxide (NaOH), it only took 30 days to degrade. Even when it 1 ydr9 lyzes it doe dot follow a first order kinetics a s PHMB by its very nature is not a simple hom geneous polymer but is a polymer with repeating hexamethylene links the number of which aries.
.

Adsorption/Desorption PHMB was found to rapidly absorb to soils (MRID nos. 00 1 77931 and 93191024). In a batch equilibrium study for soil 

# e 4C]PHMB was rapidly adsorbed 'f ith equilibrium reached within the first 16 hour shaking period. However, no Kacts or 

### Koc were reported. Similarly in an aged soil column leaching study (MRID# 

# 9 ) 910 !24) radio -labeled [ 14C]PHMB was incubated with calcareous clay loam, coarse sand, b d course sandy loam soils for four weeks under aerobic conditions. No radioactivity was

### det~**1** ted in the leachate when 35 em long soil columns were leached with 68 em rain over a two mo period. About 90-95 % of the PHMB was found to stay within the top five inches of soils ove a period of two months. Even if biodegradation products are formed , they along with the p ent PHMB appear to bind very strongly to the soils and are not extractable.

3 The FDA paper reported the concentration in terms of Normality (N) and not Mol arity (M) for the reagents; in the case ofHCl and NaOH normality and molarity are one and the same. Page 8 of25In addition to looking at hydrolysis, the FDA study (Lucas, 2012) performed a screening level study on PHMB leaching using: a clay soil, a MD soil, a potting soil, a sandy soil and old concrete pieces. The presence of PHMB leaching from clay soil, potting soil, and concrete was not detected
. Only in sandy soil was the presence of PHMB detected. Bioaccumulation Since the log Kow for PHMB is very low (

-2
. 26), PHMB is not likely to bioaccumulate in aquatic organisms. Biotic Fate Aerobic Soil Metabolism In an aerobic soil me 1 abolism study (MRID nos. 00077932 and 93191023), conducted using three United States soils. PHMB degraded by only 20% at the end of one year at pHs 6.0, 7.0, and 7.5. Thirty to forty percent (30-40%) of PHMB was extracted from the soil. Thus PHMB does not biodegrade j erobically in various soils but rather stays around on the top soil. Anaerobic Soil Metabolism An anaerobic soil

### tabolism study was conducted with one soil at a soil pH of 7 (MRID nos. 00077932 and 93191022). At the end of one year only 10.6% ofPHMB was estimated to have degraded. Thus PHMB does not show any tendency to biodegrade under anaerobic soil conditions. In all the metabolis studies discussed above the product tested was Baqua cil (20% PHMB), mixed with carbon-14 ( 14C) radiolabeled PHMB. All of the metabolism studies discussed above were condu ted under non- guideline test conditions. But these studies do provide data points from which the conclusions drawn are: Biode radabili in l ctivated Stud e andActivated Stud e Inhibition Both a semicontinuous and a continuous activated sludge treatment study (Acc#234289) using radiolabeled PH:NJB were conducted in the late 1970's. The protocols for these studies differ in key aspects from cuhent guidelines, and are therefore considered supplemental. However, these studies do iJdicate that PHMB is resistant to microbial attack in activated sludge. For down-the-drain or discharge to waste treatment plants the Agency will assume PHMB is stable based on this data. If :there is more current activated sludge test data that would change this value, such data can be ubmitted for review. An activated sludge espiration rate test was also conducted in the late 1970's (Acc#234289). As with the activated sludge studies, the protocols for this study differ from current practices for an**acti ated**  sludge respiration inhibition (ASRI) study and therefore provide supplemental information. However, the information from the study is sufficient for use in the assessment and no nef testing is required at this time. The study demonstrated that at concentrations of 40 mg/L and higher the sludge process is affected such that respiration is affected and pH becomes more basic (7 .5

- 8.0). This latter effect can lead to inhibition of Page 9 of25nitrification and accumulation of suspended solids. Depending on the concentration of suspended solids a significant portion of the PHMB can potentiall be discharged to surface waters. No effect was observed on anaerobic sludge digestion froJ 56 to 250 mg/L. More recent literature studies by O'Malley et al. (2006, 2007) h ave shown that PHMB does biodegrade in the presence of certain microbes. However, th degradation is slow and even after 60 days, the degradation amounted only to 29%
. Water Quality PHMB is not identified as a cause of impairment for any water b odies listed as impaired under section 303(d) of the Clean Water Act, based on

### informatio**pro ided**  at the Agency's National Pesticides Cause oflmpairment of Waters website (searc ed AprillO, 2011) 4

. In addition, no Total Maximum Daily Loads (TMDL) have been dev loped for PHMB, based on information provided at the Agency's National Pesticide TMDL**b** site (searched AprillO , 2011 ) 5

. More information on impaired water bodies and TMDLs 

### dm be found at http://www
.epa.gov/owow/tmdl/
. The Agency invites submission 6f w a ter quality data for this pesticide. To the extent possible, data should conform to the qualitkr standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Wdter B ody and Other Wa te r Quality Data in OPP's Registration Review RiskAssessment and Management Process (see : http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1 -4sop .pdf ), in order to ensure they can be used quantitatively or qualitatively in pesticide risk assbsments. Drinking Water Assessment No drinking water exposure assessment has been performe for PHMB antimicrobial uses in previous assessments. The Agency does not anticipate the eed to perform a drinking water exposure assessment for PHMB uses as part of the registrati9n review assessment. While PHMB uses may result in discharges to surface waters, PHMB is expec ed to be removed from water either attaching to sediment and humic acid in the environme h t or removed during water treatment and therefore presence of this substance in drinking watefi s not considered likely.

4

. http://iaspub.epa.go v/tmdl waters I0/attains nati on cy .cause detail 3 0 3 d ?p cause g ro up id=885 5 http ://ia spub. epa.gov/tmdl waters I0/attains nati o n.tmdl pollutant detail ?p pollutant gro up id=885&p po llutant g

roup name=PESTICIDE S Page 10 of 25

### C. Ecological Effects Summary A summary of submitted ecological effects data for various PHMB polymer dispersions is provided in Table 3. There is no major degradate of concern . PHMB polymer dispersions tested to date demonstrate low toxicity to birds and mammals and high toxicity to freshwater invertebrates and very high toxicity to fish. All submitted ecological toxicity studies were conducted with a 20% a.i. solution of PHMB, which is the technical formulation, and values were adjusted to 100% a.i. to classify the studies according to relative toxicity. Limited additional data was found using EPA's ECOTOX database
. In the registration review a quantitative ecological risk assessment will be conducted for use patterns which result in discharges ofPHMB to aquatic systems (e.g. cooling towers, paper mills, consumer products, oil well development uses). UsJ patterns such as cooling towers and consumer products will result in continuous, chronic exposfre of aquatic organisms and such exposures can occur in both freshwater and estuarine/ma ] ine waters. As different technica grade PHMB products contain a mixture of polymers of differing chain length and distribution ! toxicity is expected to potentially differ between the 20% PHMB (historic test substance) containing lower molecular weight polymer dispersions of PHMB as compared to higher molecular weight polymer dispersions of PHMB (20% and 96.3% PHMB technicals). Essentially all ofthe effects studies have been conducted with Vantocil IB, Vantocil P, and Baquacil which are 2Q% products containing lower molecular weight polymer chains of PHMB (characterization information oftest substance is average of n=4.5 to 5.5 mers). The 96.3% PHMB is characterizJd as having a distribution containing higher molecular weight chain polymers with an average of 12 mers. Information bridging the toxicity of these distributions with chain length has not been provided, so there is uncertainty in the effects characteristics of the longer chain polymers. Table 3. Summary of Submitted Ecological Effects Toxicity Data for PHMB Study Type/**Tes~** MRID/ GLN (equivalent 850 Substance Species Endpoints Study Status/ GLN)/ Toxicity Study conditions (% PHMB) Classification! ']ferrestrial Animal Acute and Chronic Toxicity BaquJ cil Mallard duck LD 50 : > 502 mg a.i./kg-bw MRID 00027491/ Acute-Avian Oral/ Tec,cal (Anas (> 2510 mg t.s./kg

-bw) Acceptable/ 71-1 (850.2100)/ platyrhnchos), (20 

## i) 20 weeks old, N=10 (no mortality) At most slightly toxic Northern bobwhite LC 50 : > 1124 ppm a.i. MRIDs 00041382 and

(C. virginianus), (> 5620 ppm t.s .) 93191002/**Baqu~cil** 14 days old, 23 Acceptable/ Acute

- Avian Dietary/ Techn cal grams, N= 10 (no treatment related mortality) At most slightly toxic 71-2 (850
.2200)/ (20 ) Mallard duck LCso> 1124 ppm a.i. MRID 00027492/ (A. platyrhnchos), (>5620 ppm t.s) Acceptable/

14 days old, 226 At most slightly toxic

grams, N=50 (no mortality) Acute-Mammalian Technical Laboratory rat MRID 00030220/ Oral/ V antooil P LD50 : 2747 mg a.i
./kg-bw 870.1100 (20
.2 % ) (Rattus norvegicus) Slightly toxic

Page 11 of25I 

# I Study Type/ Test MRID/ GLN (equivalent 850 Substance Species Endpoints Study Status/ GLN)/ Toxicity Study conditions (% PHMB) Classification! Chronic

- Mammalian Parental/Systemia NOAEL I Reproduction and LOAEL Fertility Effects/ Technical Laboratory rat 60012000 mg a . t./kg

-diet MRID 436174011 870.3800 Vantocil P**~** 69.6 I 238.9**g/kg bw;**  NA/ (20.2%) (Rattus norvegicus)**~** 71.3 I 270
.5 rrg/kg-bw) Acceptable Reproductive and OffsP,ring NOAEL: >2000 m a.i
.Mg-diet Freshwater Aquatic Animal Acute and Chronic T o xicity Acute

- Freshwater Fish/ Technical Rainbow trout 

# 96

- lrr LC,: 0.025 f ppm a.i. 72

- 1 (850.1075)/ Vantocil P (Oncorhynchus MRID 43949001/ (20%) + Acceptable flow

-through 14C

-PHMB my kiss) (measure ) Very highly toxic (26%) 2
.21 grams, 53 mm 

### r Acute

- Freshwater Fish/ Baquacil Rainbow trout 96

-hr LC 50 : 0 .11 lppm a.i. MRID 111368 Test# 72

- 1 (850.1075)/ Technical (Oncorhynchus 2746/ (20%) my kiss)**(measure )**  Supplemental/ static 0.46 grams Very highly toxic Acute

- Freshwater Fish/ Technical Rainbo w trout 96-hr LCso: 0
. 88 l mg a.i.IL MRID 00074296/ 72

- 1 (850
. 1075)/ Vantocil P (0. mykiss), (4 .4 mg t.s.IL) SupplementalJ./ flow-through (20%) 3.9 g, 64mm (nominal/ mea**ured ~**  Highly toxic Acute

- Freshwater Fish/ Formulation Rainbow trout 96

-hr LC 50 : 2.44 mg a.i
./L MRID 00077928/ 72

- 1 (850.1075)/ Vantocil IB (0. m ykiss), (12.2 mgt. ./L)**Supplemental~/** flow-through (20%) 16.4 g, 10.5 em (nomina J Moderately toxic Acute

- Freshwater Fish! Formulation Bluegill sunfish 96

-hr LC 50 : 0.11

## g a.i
.IL MRID 42722101 with 72

- 1 (850
. 10 75 )/ Vantocil IB (L. macrochirus), (0. 57 mg t.s.IL) addendum 437597 011 flow-through (20%) 1.18 g, 38 mm (nominal/measur d stock) Unacceptable/ Acute

- Freshwater Fish! 96

-hr LC 50 : 0.13 fllg a.i./L MRID 00077929 72

- 1 (850
. 1075)/ Formulation Bluegill sunfish (0 .67 mg t.s ./L) (Ace# 234289 )/ Vantocil IB (L. macrochirus), (nominal Unacceptable (low Static (20%) 0.39 g, 64mm Probit slope : IJ .714 DO) Acute-Freshwater Fish/ Technical B luegill sunfish 96-hrLC50 : 0.18 lrtg a.i. /L MRID 00074295/ 72

- 1 (850.1 075)/ Vantocil P (L. macrochi rus) , (0.91 mg t.s ./L) Supplemental1/ Static (20%) 0
.44 grams, 34 mm (nominal 1 1 Highly toxic Acute

- Freshwater Fish! Baquacil Bluegill sunfish MRID 111368 Test # 72 -1 (850
. 1075)/ 96

-hr LC 50 : 0
. 34 mg a.i./L 2745/ Technical (L. macrochirus), (measured) Supplemental/ static (20%) 0
.53 g Very hi ghl y toxic Acute

- Freshwater Fish/ Baquacil Bluegill sunfish 96

-hr LC 50 : 0.44 fg a.i
./L MRID 00111368 Test 72

- 1 (850.1075)/ Technical (L. macrochirus), (2.2 mg t.s.IL) # 2469/ (20%) 0.76 g (nominal)-chemic I samples Supplemental/ static awaiting analysis Very highly toxic Acute

- Freshwater 48

-hr EC 50 : 0.036 mg a.i./L MRID 000779 29 Invertebrate / Formulation Waterflea (0. 18 mg t.s.IL) (Ace# 234289)/ 72

-2 (850.1010) Vantocil IB (Daphnia magna)**(nominal ~**  20% a.i. <24 hours old 

# I Supple mental/ Static Slope: 3.456 Very highly toxic
Page 12 of 25Study Type/ Test MRID/ GLN (equivalent 850 Substance Species Endpoints Study Status/ GLN)/ Toxicity Study conditions (% PHMB) Classification1 Acute

- Freshwater MRID 4168 7 0-02 and Invertebrate / Waterflea 48

-hr EC 50 : 0
.09 mg a.i./L 42149902/ 72

-2 (850
. 1010) (Daphnia magna) (0.45 mg t.s .IL) Supplemental / < 24 hours old (nominal) Very highly toxic Static l· . . I ToxiCity cat e gory IS based on value expressed as the active mgred1ent. 2 This study was conducted to**pri arily**  observe time to death. There were two parts this experiment. One part consisted of a single**exposu e**  level where 100% of exposed organisms died by 96 hours, which is not useable for the risk estimation models that wit be used in the risk assessment. The second component is classified as supplemental because sublethal e ects were not monitored, no treatment levels had partial kills, the particulate matter and organic carbon co ncen ation of the dilution water is not known, and the concentrations in exposure tanks were not analyzed. Joriginally the study was**classifie~** as Acceptable, but a subsequent review reduced the classification to Supplemental. While the concen ations were measured and documented to be stable in stock solutions feeding the flow

-through system, no measure ents were made in the test chambers. Additionally, the particulate matter and organic carbon concentration in thf water was not reported and is unknown. For this compound this is a critical parameter which can affect bioava lability and test results. 1originally the study was classifieo as Acceptable, but a subsequent review reduced the classification to Supplemental because of lo w diss 1 Ived oxygen and no analytical confirmation of PHMB concentrations
. Table 4. Summary of**Pu~lic** Ecological Effects Toxicity Data for PHMB Study Type/ Test GLN (equivalent 850 Substance Species Endpoints Citation GLN)/ Study conditions (% PHMB) Acute

- Polychaete worm Estuarine/Marine Not 48

-hr
. LC 50 : 10
.9 (Platynereis Hutchinson et al., 1995 Invertebrate reporter dumerilii) (95% CI 8.43

- 14.5) Non

- guide!ine



## . . . . Tox1c1ty to Terrestnal AliJ/mals

In order to estab ish re toxicity of PHMB to birds and conduct an ecological risk assessment for the registered antimicrobial use patterns of PHMB, the following tests are required using technical grade material: two avian acute oral (LD 50) studies one with an upland game species and another with a waterfowl species (preferably the bobwhite quail and mallard duck, reSpectively) and one subacute avian dietary study (preferably with the bobwhite quail). There are two technical grade products for PHMB, one with a declared 20% active ingredienl t content and one with a 96.3% active ingredient content. Submitted avian toxicity studies and their results are presented in Table 3. Acute oral testing with one aviaf species and subacute dietary testing with two avian species using the 20% PHMB tecllf ical grade material has been conducted
. Tests with the 96
. 3% PHMB technical grade material do not exist. The studies conducted using the 20 % technical grade mate ! ial were conducted as limit tests for the test substance rather than as Page 13 of 25the active ingredient, and therefore do not provide acceptable limit tests for the active ingredient (i.e., 502 mg a.i.lkg

-bw versus 2000 mg a.i.lkg

-bw for avian acute oral toxicity testing and 1124 mg a.i.lkg-diet versus 5000 mg a.i./kg

-die for avian subacute dietary testing). Therefore, avian acute oral toxicity testing of the 20% TGAI with an upland game bird is still needed to evaluate risks and hazards from ! industrial processes and water system antimicrobial use patterns and testing of the 96.3% TGAI with either an upland game bird or waterfowl species is still needed. Testing of

### e 96.3% TGAI with an upland game bird, either as a limit test (i
. e., 2000 mg a.i.lkg

-bw) or definitive test would provide PHMB information usable for both the 20% and 96.3% TGAI. PHMB technical grade material (20% active ingredient) is l lassified as practically nontoxic to birds on a dietary basis (LC 50 >5 620 mg t . s.lkg-diet**an ~**  for waterfowl on an acute oral basis (LD 50 

### > 2510 mg t.s.lkg

-bw)
. However, PHMB itself cannot be classified as practically non-toxic because the active ingred ent

### as not been tested up to the limit exposure concentration (LCso > 5620 mg t.s .lkg-di t) or dose (LD 50 > 2000 mg a.i.lkg-bw). Mammals Laboratory acute and reproductive mammalian toxicity dat discussed in the Human Health Assessment is used to assess hazards and risks to mammalian wildlife, the specific values that will be used to assess acute and reproductive effect s to mammalian wildlife are summarized in Table 3. The acute oral LD 50 for PHMB i to rats was determined to be 2757 mg a.i.lkg

-bw (MRID 00030220) and the reproduction NOAEL was determined to be 600 mg a.i.lkg

-diet based on parental systemic effects,

### ~ affect on reproduction was observed at the highest dietary concentration tested (2000 nig a.i.lkg

-diet) (MRID 43617401). Wild mammal testing is required on a case-by- dse basis, depending on the results of these lower tier mammalian studies, intended use h attem, pertinent environmental fate characteristics and exposure- the need fer such testing has not been identified at this time
. Based on the acute oral rat data PHMB is classified as sligh ly toxic to mammalian wildlife. Toxicity to Freshwater Aquatic Animals Acute Effects In order to conduct a hazard and risk assessment for PHMB i to freshwater fis h, the minimum data required is two acute toxicity tests: one warnt water and one cold water species. The preferable cold water species is rainbow trout and the preferable warm water species is the bluegill sunfish. Several acute toxicity

### ~e**sts** for a warmwater fish , the bluegill sunfish (Lepomis macrochirus), and a coldwater fish, the rainbow trout using a I 20% PHMB technical grade material of PHMB and a 20% PHMB formulation were submitted and reviewed by the Agency and are summarized in Table 3. Most of these were not acceptable for a variety of reasons, but one of the major issues that all of these studies had in common was the lack of analytical confirmation of the PHMB exposure concentration of PHMB throughout the duration of the study. PHMB can sorb to a Page 14 of 25variety of materials reducing the exposure concentration such that any results based on nominal concentrations or on stock concentrations alone rather than in test chamber analytical results may overestimate the exposure concentration, resulting in an underestimation of the toxicity of PHMB
. Additionally, analytical results from several studies conducted under static conditions demonstrated that PHMB exposure concentrations were not stable under static conditions. There is one acceptable acute freshwater fish study with rainbow trout which was conducted under flow through conditions and the concentration of PHMB was measured in test chambers. The 96-h LC 50 of 0
.0254 ppm a.i. (MRID 43949001) from this study results in PHMB being classified as very highly toxic to freshwater fish. None of the blue gill studies provided acceptable test results. There were bluegill studies that have been previously identified as acceptable but these were either conducted as static studies and analytical results from these or other studies have demonstrated that PHMB concentrations are not stable under such conditions. The data requirement for acute freshwater fish testing with PHMB with a warm water species is not fulfilletl. The minimal testing L quired establishing the acute toxicity of PHMB to freshwater invertebrates is a freshwater aquatic invertebrate toxicity test, preferably using first instar Daphnia magna or e rly instar amphipods, stoneflies, mayflies, or midges. There are two freshwater D. magna studies available but both studies provide only supplemental information
. Studies were previously identified as acceptable but these studies were conducted under static conditions which have been demonstrated under similar study conditions to be unstable, therefore results from these studies are expected to underestimate toxicit/y
. The data requiremen for acute freshwater fish testing with PHMB with a warm water species is not fulfillep. Chronic Effects No chronic data is a ailable for PHMB with freshwater fish. Because uses of PHMB will result in repeated or · n some cases continuous discharge of the antimicrobial to aquatic environment a fish early life stage test with PHMB is required. There should be an acute toxicity test using the same test substance available for the same species. The more sensitive species of the two tested, rainbow trout should be used in the early life stage test. The lower**~ier** early life stage test rather than a higher tier fish full life cycle test is anticipated at this

### ti**e** because there is no indication at this time that effects on reproduction (e.g

. , fer,ilization, fecundity) would be more sensitive than estimates of chronic effects from the early life stage test. No chronic data is a ailable for PHMB with freshwater invertebrates. Because uses of PHMB will result in repeated discharge or continuous exposure of PHMB to the aquatic environment a life cycle test with PHMB is required.

Page 15 of 25Toxicity to Estuarine and Marine Animals Acute Effects 1 No toxicity data for estuarine/marine animals has been subnritted. For uses where the antimicrobial is expected to reach estuarine or marine envir f nments, one estuarine/marine acute fish toxicity study, one acute crustacran toxicity study, and one mollusk study are required. While labeling precludes use**~** this product in oil recovery systems in or, over or near marine and/or estuarine oil**field ~**  there are a number of other industrial water and process systems in addition to oil recovfry systems that do not preclude the discharge of effluents or spent fluids to waste ater treatment plants which discharge to marine or estuarine waters. For example, there are cooling towers and paper mills that discharge to estuarine and marine waters.**Additionall ,**  there are a number of
. domestic waste water treatment plants that discharge to estur rine or marine waters, such that use in household and consumer products can result in df scharge of this chemical to estuarine and marine waters. Therefore estuarine/marine organism fish and invertebrate data is needed. A public literature**se~ch cond~~ted**  for the. 2004 RED**fo~n~** a study using**~e** marine polychaete, Platynerezs dumerzlu. InformatiOn on the specific PHMB matenal tested and I whether results are reported in terms of the test material or**HMB** are not provided. This information therefore provides at most antidotal informatiorl. Chronic Effects No chronic toxicity data for estuarine/marine animals has b en submitted. For uses where the antimicrobial is expected to reach estuarine or m akine environments, and chronic or repeated exposure conditions exist chronic data 

# £ r 1r a fish and aquatic invertebrate species are required. The Agency proposes usi g 

### anJ acute-to-chronic ratio (ACR) approach to estimate these values rather than ask for the data at this time. This approach would be contingent upon receiving freshwater fis and aquatic invertebrate chronic data to allow calculation of ACR values for a fish

### d**in ertebrate** **,** and contingent upon receiving acute estuarine/marine fish and invertebrate data to which these ACR values would be applied. Toxicity to Aquatic Plants

No algal toxicity data have been submitted for PHMB. For the ecological risk assessment, including an endangered species assessment for all uses , the Agency anticipates needing the algal toxicity data for PHMB with four species: a green alga, a freshwater diatom, a saltwater diatom, and a cyanobacterium. Vascular, Nonrooted No toxicity testing with an aquatic vascular Lemna sp . has been submitted for PHMB. One test with PHMB is required
. Page 16 of 25Adverse Ecological Incidents There are no reported incidents in the Agency's Ecological Incident Information System (EllS) regarding PHMB. The absence of documented incidents does not necessarily mean that such incidents did not occur. 

### E. Ecological Effects Risk Assessment An ecological risk assessment was not conducted previously on PHMB's use patterns described in this document. PHMB 's uses that have potential for environmental exposure are discharges from industrial pfcesses and water systems, specifically: use in pulp and papermill process water systems, cool" g towers, oil well development and process waters, residential, commercial, and institutiona consumer products (e.g

. , pools, spas, laundry detergent, cleaning products) and industrial uses with down

-the

-drain discharges. The Agency needs to conduct environmental fate and

### ~~c~!~ical risk assessments for uses that potentially pass through waste water treatment plants (w '; l lPs) and may be discharged into terrestrial and aquatic environments. Discharge directly to the environment may also occur from swimming pool water being discharged directly to the ground or to storm drains. The Agency has not previously assessed the potential for environmental exposures from the discharge of treated swimming pool water. In most cases, pesticides used in pools for the purpose of disinfection are dissipated in the process of providing the peshcidal effect (e.g., chlorine

-based treatments). However, for more persistent chemicals, such aJ PHMB, the Agency has determined that such an assessment should be included in the registration review assessment. Additionally given the persistence of PHMB, the Agency plans on evaluafng releases to the environment from architectural paints and coatings applied to facades and other exterior surfaces due to leaching and washoff from rain, building wash water or

### irrig~tion overspray contacting these surfaces. For this ecological risk assessment, including an endangered species assessment for all uses, the Agency anticipates needing the ecotoxicity data outlined on pages 14 to 16 of this document. The Agency has not

# onducted a quantitative ecological risk assessment for PHMB previously that supports a complete endangered species effects determination. The ecological risk assessment planned during registration review will allow the Agency to determine whether PHMB uses have "no effect or "may affect" federally listed threatened or endangered species (listed species) or their desi ned critical habitats. When an assessment concludes that a pesticide's use "may affect"ja listed species or its designated critical habitat, the Agency will consult with the U.S. Fish aljld Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriate.

Page 17 of25

### F. Environmental Fate and Ecotoxicity Data Gaps and Anticipated WorkDown-the-drain environmental fate studies are supplemental studies and do not provide adequate information that can be used to ascertain a dose-response curve of the relationship between concentration of PHMB and respiration inhibition effects to activated sludge microorganisms. Although a quantitative assessment of risks to**act vated**  sludge microorganisms is not currently within the scope of ecological risk assessments for 4 ntimicrobial pesticides , consideration of potential adverse effects to wastewater treatment**ant** microorganisms is included. Therefore an Activated Sludge Respiration Inhibition (ASRI) test is required. While the aerobic and anaerobic metabolism studies are supplemental, the ; · nformation from these studies is sufficient to identify PHMB as stable so no additional stu ies are required at this time. If there are more current studies that have been conducted the Age y recommends this information be submitted. The Agency anticipates needing the foll wing environmental fate study for each TGAI (i.e., 20% and 96.3%): • Activated Sludge Sorption/Desorption

- TGAI (OCSP 835.1110); and • Activated Sludge Respiration Inhibition (ASRI) test
- TGAI (O:EjCD 209, OCSP 850.3300). To be able to determine both acute and chronic risks to**aqu tic**  organisms from discharges to both freshwater and estuarine/marine waters addition'll inf0rmation on toxicity of PHMB to aquatic plants and estuarine/marine organisms are needed
. The Agency anticipates needing the following ecological effect studies for each TGAI**(20~** and 96.3%). For aquatic organisms, if the 20% and 96.3% TGAI tests with acute freshwater rish, freshwater invertebrate, green algae, and whole sediment Hyallela azteca toxicity tests dem? nstrate that toxicity is bridgeable between the lower molecular weight and higher molecular weight polymer dispersions, the remaining effects tests are needed only for one of tHe TGAis. Additionally, if one of the dispersions is more toxic, the remaining tests can be con ucted with the more toxic form only. However in the latter case, the toxicity of the TGAI not ested will be assumed to be that of the more toxic TGAI for purposes of the risk assessment.
• Avian Acute Oral Toxicity, Upland Game Species

- TGAI (G I LN 850.2100 or OECD 233); • Freshwater Invertebrate Acute Toxicity

- TGAI (OCSPP 85 .1010); • Mollusk Shell Deposition Toxicity study or Mollusk Embryo Larvae Toxicity studyTGAI (OCSPP 850.1025 or OCSPP 850.1055 , respectively) • Freshwater Fish Acute Toxicity, Warm Water Species

- TGAI (OCSPP 850
. 1075); • Estuarine/Marine Fish Acute Toxicity study

- TGAI (OCSPP 850.1075); • Freshwater Invertebrate Life Cycle study-TGAI (OCSPP 850.1300) ; • Freshwater Fish E arly Life Stage study using the most acutely sens itive fish

- TGAI (OCSPP 850.1 400); • Estuarine/Marine Shrimp Acute Toxicity study using the saltwater mysid

- TGAI (OCSPP 850.1035) ; Page 18 of 25• An Estuarine/Marine Shrimp Chronic Toxicity Test

- TGAI (OCSPP 850.1350); • An Estuarine/Marine Fish Early Life Stage study

- (OCSPP 850
. 1400); • Seedling Emergence and Growth Tier II for rice

- TGAI (OCSPP 850.4100); • Aquatic vascular plant growth Tier II data for a Lemna sp. - TGAI (OCSPP 850.4400); • Algal toxicity Tier II data for a green alga species

- TGAI (OCSPP 850.4500); • Algal toxicity Tier II data for a freshwater diatom species

- TGAI (OCSPP 850.4500); • Algal toxicity Tier II Idata for a marine diatom specie

- TGAI (OCSPP 850.4500); • Algal toxicity Tier II data for a cyanobacterium species

- TGAI (OCSPP 850.4550); • Chronic Whole

# Sedi**ent** Freshwater Invertebrate Toxicity Test with the amphipod Hyallela azteca
- T1 AI (Special Study); • Chronic Whole**edi ent**  Freshwater Invertebrate Toxicity Test with the midge (Chironomous sp.)

- I TGAI (Special Study); and • Chronic Whole

# edi**1jll ent**  Estuarine/Marine Invertebrate Toxicity Test with the amphipod Leptochirus plumulosus)

- TGAI (Special Study). For the least acutely sensitivf estuarine/marine species a chronic value may potentially be estimated using an acute-to
-chronic ratio (ACR) approach. If the ACR derived from the estuarine/marine chronic test conducted for the more sensitive estuarine/marine organism (based on the acute results) does not differ from ACRs calculated from freshwater species, the chronic test for the less sensitive organism may be estimated using existing ACRs and the acute v alue for the less sensitive species
. F om the Office of Water (OW) guidance ACRs within a factor of ten are considered not to differ significantll. Also, please note that on Ju j e 27, 2012, EPA announced certain revisions in harmonized guideline series 850

- Ecological Effects Tests

- including removal of the Tier designation on 850.4100 (Seedling Emergeiilce and Seedling Growth), 850.4400 (Aquatic Plant Toxicity Test Using Lemna Spp.), 850.44SO(Aquatic Plants Field Study) and 850
.5400 (Algal Toxicity)
. For more information see "Final i Test Guidelines; OCSPP 850 Series; Notice of Availability" 77 FR 38282,June27,20127

. • The Algal Toxicity s udy (Public Draft OPPTS 850
.5400) was replaced by the following harmonized guidelines: OCSPP 850.4500: Algal Toxicity and OCSPP 850.4550 Cyanobacteria (AnaU aenaflos -aquae) Toxicity;

• The S eedling Emergy nce and Growth, Tier II study (Public Draft OPPTS 850.4225) was replaced by the f ollowing harmonized guideline: OCSPP 850.4100: Seedling Emergence and Seedling Growth ; and
• The Modified ASRI lest (Public Draft OPPTS 850.6800) was renumbered OCSPP 850.3300).

6 http://water.epa.gov/scitech/swguidance/standards/criteria/aglife/upload/85guidelines.pdf 7 http:/ /www.regulations.gov/#!dot umentDetail ;D=EP A

-HQ- 2009-0154-0028 Page 19 of 25The OPP, the ORD and the OW are actively working on deriving a common effects characterization methodology for use in ecological assessments of**hemicals** by EPA to meet the mandates of the Clean Water Act (CWA) and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Currently the Agency does not have a fixed timeframe for this effort but are actively working with OW and ORD on follow-up actions that will advance harmonized methodologies. The Agency's web page 8 on harmonization of co mon effects will be updated as the effort progresses. Additional Data Needs Facility Emissions to WWTP Modeling For assessing the fate of PHMB to receiving waters from inl::l.ustrial process water uses of PHMB such as at pulp and paper mills, for recirculating codling towers, and oil well development the Agency anticipates using the available en l iroruhental fate information from guideline studies for PHMB and the following emission scdnarios.

• To estimate exposure related to releases of PHMB to

# do**estic** wastewater treatment plants from uses such as PHMB in detergents, laundry nnses and cleaners the Agency will rely on the Office of Chemical Safety and *olluf ion Prevention (OCSPP) model, Exposure and Fate Assessment Screening Tool (E-FAST, version 2.0, 2007, or EFAST2). From this model, the Agency will use the 'Do'Yn-the

-Drain" (DtD) module, which is designed to evaluate releases to dome tic wastewater treatment plants
. It is suitable for all the indoor sources of PHMB that could potentially be exposed through a consumer "down-the-drain" scenario The model provides screening level estimate concentrations of chemicals in
.urface water that may result from household uses and the disposal of consumer prod cts into wastewater using a few simple input parameters (production volume and fraction of the chemical removed during wastewater treatment). 

## •



# •

• Potential environmental releases and associated exposu!s of concern for antimicrobial uses related to the Pulp, Paper, and Board Industry will be those identified in "Emission Scenario Documents on Pulp, P per, and Board Industry", Number 23 of OECD Series on Emission Scenario

### Doc**ments** dated July 8, 2009. Potential environmental releases and associated exposu+s of concern for antimicrobial uses related to the Oil and Gas Well**Prod ~ct** **ion** Industry will be those identified in the latest version of the OECD Emission S Genario Document for the Oil Well Production Industry or those identified in the

### lates**~** version of Generic Scenarios developed by the Chemical Engineering Branch of EPA(OCSPP/OPPT/CEB (Chemical Engineering Branch). On

- shore operations**sume** potential for disposal of drilling fluids and produce water to public or industrial waste treatment facilities and off

- shore operations assume emissions directly to the surrounding water, posttreatment for removal of oil. 

### I Potential environmental releases and associated exposures of concern for uses of antimicrobial uses related to recirculating cooling towers will be assess ed using the Generic Scenarios for recirculating cooling towers developed by the Chemical

8 www.epa.gov/oppefed I /cwa fifra effects methodology/scope.html Page 20 of25Engineering Branch of EP A/OCSPP/OPPT/CEB and modified for use for antimicrobials by the Antimicrobial Division. • Potential environmental releases and associated exposures of concern for antimicrobial uses related to adhesive preservatives will be those identified in "Emission Scenario Document on Adhesive Formulation", Number 20 of OECD Series on Emission Scenario Documents dated April24, 2009; • Potential environmental releases and associated exposures of concern for antimicrobial uses related to paints and coating preservatives will be those identified in "Emission Scenario Document on Coating Industry (Paints, Laquers and Varnishes)" , Number 22 of OECD Series on Emission Scenario Documents dated April 24, 2009; and Facility information eeded to estimate aquatic exposures from emissions to WWTP for each emission scenar ro and directly to water include the following: • The number of pt lp and paper mill sites using PHMB or the maximum annual**pro?uc~ion volm** **e** of PHMB used in pulp and paper mills in the United States and its terntones; • The number of

# circulating cooling tower sites using PHMB or the maximum annual**pro?uc~ion** volu, e of PHMB used in cooling towers in the United States and its terrttones; • The number of o·l well development sites using PHMB or the maximum annual production voluiY,e of PHMB used in oil and gas well development in the United States and its te, itories; • The number of adhesive industrial or manufacturing sites using PHMB or the maximum annual production volume of PHMB used in the adhesive formulation industry in the United States and its territories; • How many of eaa:h of these facilities has on-site and/or off

- site wastewater treatment. In the absence of inf l rmation on the number of these facilities that use PHMB and how many of these facilid es have on-site and/or off-site wastewater treatment, the Agency will assume that all

### ch facilities in the United States have the potential to use PHMB. During the public coL entJ'"riod on the Preliminary Work Plan, the Bay Area Clean Water Agencies**(B~CWA)** and the California Stormwater Quality Association (CASQA) 10 provided informational materials on the number of pools in existence nationally and withirl California, swimming pool discharge practices from local agencies from around the cou try, and a swimming pool discharge study. This information will be reviewed and where appropriate used to assist EPA with development of a modeling scenario for swimmihg pools.

9 In the docket as EPA

-HQ-OPP-2012-0341-007 10 In the docket as EPA

-HQ

-OPP

-Q 012-0341

-009 Page 21 of 25

### References de Paula, G. F., G. I. Netto, and L.H.C. Mattoso. 2011. Physical a* d chemical characterization of poly(hexamethylene biguanide) hydrochloride. Polymers 1 3:928

-941. Kaehn, K. 2010. Polihexanide: a safe and highly effective biguanioe. Skin Pharmacology and Physiology 223(1):7

- 16. O'Malley, L.P ., A.N. Collins, and G
.F
. White. 2006. Biodegradability of end

- groups of the biocide biguanide (PHMB) assessed using model compound 1

. Journal of Industrial Microbiology and Biotechnology 33 :677

- 684.

Page 22 of25

### Appendix A: Ecological Guideline Special Study Justifications Study Title: Chronic Freshwater Whole Sediment Toxicity Test using the amphipod

Hyalella azteca 

### Guideline Number: Special Study, Use Agency-wide guideline Test Method 100.4: Hyalella

azteca 

### 42-d Test for Measuring the Effects of Sediment Associated Contaminants on Survival, Growth, and Reproduction 

### in USEP A 2000 Methods for Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants with Freshwater Invertebrates EPA 600/R-99/064 Exposure Method: Spiked whole sediment Test Substance: TGAI Rationale for Requiring the Data No chronic spiked

- sedimentj toxicity test for a freshwater benthic amphipod has been submitted f

or PHMB. A number of use patterns of PHMB such as industrial processes and water systems, oil and gas well production ystems, and consumer products may result in PHMB reaching aquatic freshwater sediment through discharge to waste water plants and subsequent discharge to surface waters. PHMB is expected to sorb to organic and inorganic material which would be associated primarily wifh the sediment in the environment. Sediment benthos may be exposed chemicals in the sediment vik pathways not accounted for in water only studies, such as ingestion of sediment. Chemical s tha partition to sediment and are persistent in the sediment have the potential to pose a chronic risk to sediment benthos. PHMB is highly stable in the environment and is not expected to readily degrade from the sediment and therefore uses and environmental fate pose a potential chronic 1risk to estuarine/marine sediment benthos. Prior to conduct of the stud , the test design and protocol must be submitted for Agency review and approval. The preferred 1 sedimen t is formulated, guidance for the formulated sediment can be found in OECD 218 Sediment

-Water Chironomid Toxicity Test using Spiked Sediment. Based on test variabilit for the endpoints of concern (includes reproduction) and the need to establish a NOAEC/LOAEd the following number of replicates and test animals are recommended for this te st: 1l ireplicates per treatment ( 4 for 28

-d survival and growth and 8 for the remainder of the tes t)

### wi**~** 10 neonates per replicate. For alternative test designs the protocol should discuss the power of Jlle test. 

### Practical Utility of the Data 1. How will the data be us e'd? Data from sediment toxicity studies will be used to estimate potential chronic risks to freshw ater benthic organisms associa te . with uses of PHMB. Data from sediment toxicity studies will be compared to estimated sedillllent chronic exposure concentrations to evaluate the potential for PHMB to adversely im p act Jurvival, reproduction, and growth of sediment invertebrates. 

### 2. How could the data impL t the Agency's future decision-making? If the data indicates that reg J " stered PHMB usage may pose a risk of adverse effects to non-target benthic organisms aboVie th Agency Level of Concern, the Agency may explore decision options to mitigate this risk. The lack of these data will limit the flexibility the Agency and registrants h ave in coming i to compliance with the Enda ngered Specie s Act, and could res ult in use restrictions f or PHMB J hich may otherwise be avoided, or which are unnecessarily severe. Page 23 of25

### Study Title: Chronic Freshwater Whole Sediment Toxicity Test using a midge, 

### Chironomus sp. Guideline Number: Special Study, Use Agency-wide guideline Test Method 100.5: Lifecycle Test for Measuring the Effects of Sediment-Associated Contaminants on 

### Chironomus dilutus or C. 

### tentans in USEPA 2000 Methods for Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants with Freshwater Invertebrates EPA 600/R-99/064 Exposure Method: Spiked whole sediment Test Substance: TGAI Rationale for Requirin2 the Data No chronic spiked

- sediment toxicity test for a freshwater benthic rrydge**as** been submitted for PHMB
. A number of use patterns of PHMB such as industrial processes and water systems, oil and gas well production systems, and consumer products may resul in PHMB reaching aquatic freshwater sediments through discharge to waste water plants and spbsequent discharge to surface waters. PHMB is expected to sorb to organic and inorgani material which would be associated primarily with the sediment in the environment. Sedime t benthos may be exposed chemicals in the sediment via pathways not accounted for in water only studies, such as ingestion of sediment. Chemicals that partition to sediment and are persisten in the sediment have the potential to pose a chronic risk to sediment benthos. PHMB is higH ly stable in the environment and is not expected to readily degrade from the sediment and

### there**ore** uses and environmental fate pose a potential chronic risk to estuarine/marine sediment bentllos. Prior to conduct of the study, the test design and protocol must be shbmitted for Agency review and approval. The preferred sediment is formulated, guidance for

### e formulated sediment can be found in OECD 218 Sediment

-Water Chironomid Toxicity Testr sing Spiked Sediment. Based on test variability for the endpoints of concern (includes reprpduction) and the need to establish a NOAEC/LOAEC the following number of replicates and tes t animals are recommended for this test: for the midge test with C. dilutus 16 rept, icat9s containing 12 test organisms each (12 replicates at test initiation; 4 added at 10 days :D ' r auxiliary males). For alternative test design s the protocol should discuss the power of the test. 

### I Practical Utility of the Data 1. How will the data be used? 

### I Data from sediment toxicity studies will be used to estimate potential chronic risks to freshwater benthic organisms associated with uses of PHMB. Data from sedi0 ent toxicity studies will be compared to estimated sediment chronic exposure concentrations to evaluate the potential for PHMB to adversely impact survival, reproduction, and growth of sediment invertebrates. 

### 2. How could the data impact the Agency's future decision-mak'ng? If the data indicates that registered PHMB usage may pose a risk of j adverse effects to non-target benthic organisms above the Agency Level of Concern, the**Agenc ~**  may explore decision options to mitigate this risk. The lack of these data will limit the fl exibility the Agency and registrants have in coming into compliance with the Endangered Sp bcies Act, and could result in use restrictions for PHMB which may otherwise be avoided, or which are unnecessarily severe .

Page 24 of25Study Title: Chronic Marine/Estuarine Whole Sediment Toxicity Test using 

### Leptocheirus plumulosus Guideline Number: Special Study, Use Agency-wide guideline Methods for Assessing the

Chronic Toxicity of Marine and Estuarine Sediment-Associated Contaminants with the Amphipod 

### Leptocheirusplumulosus (USEPA 2001c) Exposure Method: Spiked whole sediment Test Substance: TGAI Rationale for Requiring the Data No chronic spiked-sediment l toxicity test for an estuarine/marine benthic amphipod has been submitted for PHMB. A nm r,ber of use patterns of PHMB such as industrial processes and water systems, oil and gas well pr9duction systems, and consumer products may result in PHMB reaching aquatic**estuar ne~5~rine**  sediments through discharge to waste water plants and subsequent discharge to**s~~ ce**  waters . PHMB is expected to sorb to organic and inorganic material which would be**as~siated** primarily with the sediment in the environment. Sediment benthos may be exposed ch icals in the sediment via pathways not accounted for in water only studies, such as ingestion of sediment. Chemicals that partition to sediment and are persistent in the sediment have the poten ial to pose a chronic risk to sediment benthos. PHMB is highly stable in the environment anti is not expected to readily degrade from the sediment and therefore uses and environmental fate pose a potential chronic risk to estuarine/marine sediment benthos. Prior to conduct of the study, the test design and protocol must be submitted for Agency review and approval. The

### preferre**~** sediment is formulated, guidance for the formulated sediment can be found in OECD 218 Sediment

-Water Chironomid Toxicity Test using Spiked Sediment. Based on test variability for the endpoints of concern (includes reproduction) and the need to establish a NOAEC/LOAE the following number of replicates and test animals are recommended for this test : 10 replicates per treatment with 20 neonates per replicate. For alternative test designs the

### otocol should discuss the power of the test. Practical Utility of the Data 1. How will the data be used? Data from sediment toxicity l studies will be used to estimate potential chronic risks
. to estuarine/marine benthic**oq anisms**  associated with uses of PHMB
. Data from sediment toxicity studies will be compar ed to estimated sediment chronic exposure concentrations to evaluate the potential for PHMB to adve 1sely impact survival, reproduction, and growth of sediment invertebrates. 2. How could the data impact the Agency's future decision-making? If the data indicates tha reg .lstered PHMB usage may pose a risk of adverse effects to non-target benthic organisms above the Agency Level of Concern, the Agency may explore decision options to mitigate this risk
. 

### IThe lack of these data will limit the flexibility the Agency and registrants have in coming iljltO compliance with the Endangered Species Act , and could result in use restrictions for PHMB which may otherwise be avoided, or which are unnecessarily severe .

Page 25 of25