REGISTRATION REVIEW DOCUMENT

PRODUCT CHEMISTRY, E NVIRONMENTAL FATE AND

ECOLOGICAL EFFECTS SUMMARY FOR TETRAKIS (HYDROXYMETHYL)PHOSPHONIUM SULFATE

Important Note on the Chemistry:

Tetrakis (hydroxymethyl) phosphonium sulfate is an organophosphate-like chemical but
has not been classified within this class of chemicals. Phos phorous is quatnerized in this chemical. It was classified as a benign and safe biocide and under EPA’s Toxics Program of Green Chemistry, THPS was awarded a Green Chemical Award in 1997 to the parent Company Albright & Wilson, now Rhodia, (EPA Document number 744K10003, June 2010, www.epa.gov ). The Agency conducted a number of open literature searches and found the following information on Dow Chemical Co. Website: 1) “THPS is manufactured in a batch process that invol ves the chemical reaction of phosphine gas with aqueous formaldehyde in the presence of sulfuric acid and water. THPS exists in equilibrium with tris (hydroxymethyl) phosphine and methylene glycol. Under manufacturing and shipping conditions, the equi librium strongly favors the formation the formation of THPS” (This reference is for the AQUCAR THPS 75 product of Dow). The Agency assumes that it is likely to contain formaldehyde as an impurity and it is likely a formaldehyde releaser. This is confirmed in a recent publication by Li Ya et al as
discussed below.

THPS degrades by the following reaction series:

[(CH 2 OH) 8 P 2 )] +2 SO 4 -2

----- Æ 2 P(CH 2 OH) 3 (trihydroxymethyl phosphine) + 2HCHO (formaldehyde) + SO 4 -2 (aq)--------------

--------------------------- ---------(1) Hence one mole of THPS produces 2 moles of formaldehyde.

P (CH 2 OH) 3 + H 2 O ---------------- ------------P(CH 2 OH) 3 O (Phosphine oxide) --------(2)

(Source: Li,Ya, Saho Shuangxi, Shi, Kaiqi, and Jaing Lan) in the J ournal of the Society of Leather Technologists and Chemists: July/August 2008: 92(4), pp 167-169. The research indicates that in the tanning pro cess of leather, THPS releases formaldehyde, and the release of formaldehyde is pH dependent. It was further determined that formaldehyde release is controlled by adding hydrogen peroxide during the tanning

process.

2Table 1: Use patterns
Chemical name Use patterns/use sites Cytec: CYPHOS B1 (77%) For repackaging and formulating antimicrobial end use products in oil field operations and systems, oil drilling muds, and packer fluids, recirculati ng water cooling towers, paper and paperboard manufacturing, air conditioning and refrigeration’s condensate water systems, air washing systems, heat exchanger wate r systems, industrial processing water, industrial fresh water systems, industrial wastewater systems, fire protection systems, service water and auxiliary systems, solution/emulsions, and laboratory equipment water baths

.

TOLCIDE PS75 (75%) Used in air cond itioning/refrigeration condensate water systems, recirculating commercial/industrial water cooling systems, heat exchanger water systems, industrial processing water, laboratory equipment water baths, and oil recovering, drilling muds packers fluids
TOLCIDE PS 50A (50%) Same as CYPHOS B1

Tolcide PS 200 (20%) Besides CYTEC CYPHOS B1 additional application sites are: Gas storage well system, well remediation operations, hydrotesting, pipeline piggi ng and scraping operation
TOLCIDEW PS70AF (70%) Same as CYTEC CYPHOS B1

TOLCIDE PS70A (70%) Same as CYTEC CYPHOS B1. In addition, Gas storage well system, well remediation opera tions, hydrotesting, pipeline pigging and scraping operation AQUCAR THPS 75 (76.5%) Same as CYTEC CYPHOS B1. In addition, Gas storage well system, well remediation opera tions, hydrotesting, pipeline pigging and scraping

MAGNACIDE 575S (50%) Oil filed waters, Drilling muds and workover or completion fluids, well stimulation and fracturing
ACUCAR THPS 75 MFG (76.5%): Same as AQUCAR THPS 75

ALL-CLEAR End-Use Formulation (2.85% THPS; 0.43%
Benzalkonium chloride) Surface Disinfectant for hard in animate non-porous surfaces: floors, walls, rails, chairs, shower stalls, urinals, bath tubs, and non-food contact surfaces, incl uding tables, and counters, homes, schools, hospitals, cafet eria, restaurant, offices,
industrial and commercial buildi ngs, exterior of structures, areas of mass gathering such as stadiums, and convention centers, or outdoor on vehicles, farm equipment and poultry premises

3Regulatory History: TBA

Table 2: Registered Active Products fo r: Tetrakis (hydroxym ethyl) phosphonium Sulfate

EPA Reg.
Number Product Name Formulation Type % Active Ingredient Registrant

68387-9 CYPHOS B1
PHOSPHONIUM
SALT Aqueous
solution 77.7 (conditionally registered CYTEC Industries, Inc

464-8127 AQUA THPS
75FW 76.6 (Registered) Dow Chemical
Co.
464-8126 AQUATHPS
75 76.5(Registered) Dow Chemical
Co.
33677-3 TOLCIDE
PS75 75(Conditionally registered) Rhodia UK, Ltd

33677-7 TOLCIDE
PS75LT 75(Conditionally registered) Rhodia UK, Ltd

4564-20 TOLCIDE
PS70A 70(Conditionally registered) Rhodia, Inc.

4564-19 TOLCIDE
PS70FA 70(conditionally registered) Rhodia, Inc

4564-RA TOLCIDE
PS50D 50 (status uncertain) Rhodia Inc

10707-57 MAGNACIDE
575S 50(Conditionally registered) Baker Petrolite Corp
4564-17 TOLCIDE
PS50A 50(Registered) Rhodia Inc.

33677-6 TOLCIDE
PS352C 35(Conditionally registered) Rhodia UK Ltd

4564-18 TOLCIDE
PS20A 20(Registered) Rhodia Inc.

4564-15 TOLCIDE
PS200 20(Conditionally Registered) Rhodia Inc.

82932-1 ALL CLEAR 3(Registered) KIDDE Fire Fighting
82932-1 ALL CLEAR 0.5(Registered)
contains ADBAC as a
second active KIDDE Fire Fighting

Based on the label searches and label analysis, the use sites/use patterns of THPS are as
follows:

4For repackaging and formulating antimicrobial end use products in oil field operations and systems, oil drilling muds, and packer fluids, recirculating water cooling towers, paper and paperboard manufacturing, air c onditioning and refrigeration’s condensate water systems, air washing systems, heat ex changer water systems, industrial processing water, industrial fresh water systems, indus trial wastewater syst ems, fire protection systems, service water and auxiliary syst ems, solution/emulsions, and laboratory equipment water baths. Surf ace disinfectant for hard in animate non-porous surfaces

Table 3. Chemical Identity

Common Name THPS

Chemical Name Tetrakis(hyd roxymethyl)phosphonium sulfate

IUPAC Name Same
Molecular Weight 406.28

PC Code 129058 CAS Registry Number 55566-30-8 Molecular Formula/Empirical
Formula C 8 H 24 O 12 P 2 S

Registration Review Case No. 5034
Registration Review Case Name THPS

Classification: Organic Derivative of quat. Phosphorous

Structure:

Science Findings:

The following tables summarize the science data for each discipline, and lists some data

gaps.

5Product Chemistry Summary

Table 4: Physical and Chemical Pr operties of Tetrakis(hydroxymethyl) phosphonium sulfate

Guideline
No. Physical and Chemical Properties Value

830.1550 Product identity and composition Refer to Table 2
830.1600 Description of materials used to produce the product CBI

830.1620 Description of production process CBI
830.1650 Description of formulation process CBI
830.1670 Discussion of formation of impurities CBI
830.1700 Preliminary analysis CBI
830.1750 Certified limits CBI
830.1800 Enforcement analytical method CBI
830.1900 Submittal of samples CBI
830.6302 Color Colorless; MRID: 466599-02 2

830.6303 Physical State Viscous liquid at 20 o C; MRID:466599-02
830.6304 Odor Antiseptic Odor: MRID: 466599-02
830.6313 Stability to sunlight, normal and elevated temperature N/A: Product is not expect ed to come in contact with either metals or metal ions during storage:
MRID: 466599-02
830.6314 Oxidation/Reduction: Chemical Incompatibility Compatible with: water, 10% monoammonium phosphate solution, zinc granules, and kerosene. Incompatible with10% potassium permanganate
solution. MRID: 466599-02
830.6315 Flammability
Flash Point Product is water-based and does not contain flammable liquids. MRID: 466599-02
830.6316 Explodability Not thermal or shock explosive: MRID: 466599-02
830.6317 Storage Stability No significant change in physical or chemical change during storage at 25 o C:MRID: 466599-02

830.6319 Miscibility N/A> product is not intended to be diluted with petroleum solvents. MRID: 466599-02
830.6320 Corrosion Characteristic No signs of corrosion or degradation of translucent plastic HDPE bottle during storage at 25 o C for12 months. MRID: 466599-02
830.6321 Dielectric breakdown voltage N/A; product is not intended to be used around electrical equipment; MRID: 466599-02
830.7000 pH 3.02 25 o C; MRID:466599-02
830.7050 UV/Visible absorption spectra Not reported:
830.7100 Viscosity 38.6 mm 2 /s at 20 o C; 18.5 mm 2 /s at 40 o C;
MRID: 466599-02
830.7200 Melting Point N/A; product is manufactured in situ and
therefore it is never isolated in a form suitable for testing as the technical grade or purified active ingredient; MRID: 466599-02; MP for the technical: 298.83 o C (EPI Suite)
830.7220 Boiling point N/A; product is manufactured in situ and therefore it is never isolated in a form suitable for testing as the technical grade or pu rified active ingredient; MRID: 466599-02; BP for the technical:
830.7300 Density/ Bulk density 1.41 g/cc 20 o C: MRID: 466599-02
830.7370 Dissociation Constants in water Product has no acid, base or alcoholic

6Guideline
No. Physical and Chemical Properties Value

functionality; MRID: 466599-02
830.7520 Particle size NA
830.7550 Octanol/water partition coefficient (K O W ) (Log K
ow ) logKo/w: ~ -4.42 MRID: 466599-02

830.7840 Solubility in water N/A: product is manufactur ed in situ and therefore is never isolated in a form suitable for testing as purified active ingredient; MRID: 466599-02
830-7840 Solubility in organic solvents in g/100
ml Not reported; MRID: 466599-02

830.7950 Vapor pressure 1.27 x 10 -5 mm Hg at 25 o C; MRID: 466599-02

Product Chemistry: Data Gaps

830.7840: Solubility in organi c solvents in g/100 ml

Environmental Fate and Transport Data Summary:

Table 4 Summarizes the Environmental Fate Data Summary for THPS (based on test guidelines and open literature)
Table 4
Environmental Fate Profile of Tetrakis (hydroxymethyl ) phosphonium sulfate (THPS)

Guideline #/Study Type Results Reference

835.2120/ Hydrolysis THPS hydrolyzed in sterile aqueous/buffered medium
and observed half lives are: 131 days at pH 5, 72 days at pH 7, and 7 days at pH 9. At all pH’s the degradation products identified (through NMR studies) were: trishydroxymethyl phosphine (THP), and in turn THP hydrolyzes to tris hydroxymethyl phosphine oxide (THPO). THPS is, therefore stable
under abiotic conditions at pH’s 5, and 7 (beyond thirty days), and can be regarded as persistent at pH’s 5, and 7. It degrades fast at pH 9. In all cases MRID#: 42236334 3

J. O’Connor: Tetrakis(hydroxymethyl)Phosphonium Sulfate (THPS): Determination of the Hydrolysis as a Function of pH: Lab Project #: 91/0737, prepared by Life Science Research Ltd; pp 78

Purity of the pesticide used for the study: 75%.

7same degradation products are produced: THP, and
THPO. The study is acceptable
Non-Guideline Study:
Mechanistic Modeling of
Anaerobic THPS
Biocide Degradation
Under Alkaline
Conditions.
The review was done internally,
and no DER was produced. This study showed that that the degradation of THPS in seawater was strongly dependent on temperature, and pH, that is, it increases as the pH and temperature increased. The study was
conducted in Persian Gulf sea water in the presence of steel coupons.
In Persian Gulf seawater (at pH 8.1, and temperature 8.1) the half life was about 5 days (initial
concentration of THPS was 100 ppm); In artificial seawater at pH 7.9, and temperature 31 C, the half life was about 6 days August 2009 , Kahli Zhao, Jie Wen, Tingyue Gu, Ardjan Kopliku, and
Ivan Cruz Materials Performance, pp 62-66 4

EPA’s Screening Model Program EPI SUITE 5 (version 4.1) lists the following product chemistry and environmental characteristics for THPS:

1. Log K ow = -20.39
2. Henry Law Constant = 1.7 x10 -6 atm-m 3 /mole
3. Half-life in air (estimat ed against hydroxy radical interaction) = 4.706 hours
4. Log K oc = 2.1533
5. Biodegradation Predictions: a) linear m odel: biodegrades fast; b) non-linear biodegradation: biodegrades fast; c) ultimate biodegradation time frame: degrades within days/weeks; d) primary biodegradation timeframe: hours/days; MITI linear model prediction: biodegrades fast; e) MITI-non-linear model predictions: biodegrades fast; f) anaerobic model pr ediction: biodegrades fast; g) ready biodegradability: YES.

Environmental Fate and Transport Conclusions :

THPS appear to be stable and persistent under abiotic conditions at pH s 5, and 7 with half lives greater than 30 days. However, at pHs above 8 (basic conditions), it degrades within 7 days. The degradation products have b een identified as: tr ishydroxymethyl phosphine (THP) and subsequently into trishydroxy methyl phosphine oxide (THPO) 8. Open literature study also shows that THPS degrades in artificial seawater (ph 7.9) with a half life of 6 days. EPA’s EPI Suite model indicat es that THPS is easily biodegradable (fast

8biodegradability) ultimate biodegradability is fast as well. Primary biodegradation half life is estimated at hours/days. Its estimated Log K ow varies from -4.42 to -20.39; it is not likely to bioaccumulate in the aquatic organisms. It does not appear to be persistent in air as its estimated half life (measured against hydroxyl radical ) is less than 5 hours. The majo r uses of this pesticides are outdoor, and it is hydrolyti cally stable, a number of environmental fate studies are triggered as the exposure form these uses will be in soils and water. Leaching and adsorption/desorption studies will clearly show if the chemical easily migrates into the
soils and sediments and Kd values determin ed from adsorption/desorption studies will show if the binding with soils is st rong or weak. Metabolism studies and biodegradability will show if the pesticide degrades in actual environmental medium. All
the studies listed below are re quired for these scenarios.

Environmental Fate and Transport Data Gaps

Its use patterns involve reci rculating cooling water system s and industrial wastewater treatments. The Agency anticipates requiri ng the following environmental fate studies: 1. 835.2240: Aquatic Photodegradation at pH 7 2. 835.1230: Leaching study from soils (migration) 3. 835.1240: Adsorption/Desorption Study (K d ) 4. 835.4300: Aerobic Aquatic Metabolism study 5. 835.4400: Anaerobic Aquatic Metabolism Study 6. 835.3110: Ready Biodegradability

Ecological Effects Data Summary:

Table 5 summarizes the eco-toxicity da ta that AD has in its data base.

Table 5 Ecotoxicity Data 6,7

Guideline #/Study type MRID#/Reference Information/Study Classification Dosing/Organism
Information Results

850.1035:
Estuarine/marine acute toxicity (Mysid Shrimp) MRID#: 442796-01 Boeri, et al (1995) Acute toxicity of THPS to Mysid, Mysidopsis hahia under flow through conditions (final report)
Core: Acceptable.
Guideline THPS administered at 0, 1.3, 2.3, 3.6, 6.1, and 10 ppm 2 replicates by 20 test organisms/level Purity: 76.8% LC 50 = 7.30

ppm; NOEAC= 3.49

ppm Moderately
toxic

850.55: Bivalve acute toxicity test MRID#: 442796-03
Boeri et al: Acute flow through Mulluse Shell Deposition Test with THPS THPS was administered at 0, 0.26, 0.44, 0.72, 1.2 and 2.00 ppm EC 50 = 1.6

ppm; NOEAL = 0.67 ppm

9(final report) Core: Accepted/ Guideline 20 test organisms/level Purity: 76.8% Moderately
toxic

850.1075:
Fish acute toxicity test (Bluegill) MRID#: 422363-25 Jenkins, w (1989): THPS: acute toxicity to Bluegill Sunfish Core/Acceptable; Guideline THPS administered
for 96 hours at 0,22.7, 37.8, 63, 105, and 175 mg/L
10 fish/treatment
level Purity: 75% 96 hour LC 50 = 98 mg/L
The test
material is slightly toxic to Bluegill
sunfish
850.1075: fish acute toxicity test (Rainbow Trout) MRID 422363-24 Jenkins, W (1990) THPS acute toxicity to
Rainbow Trout Guideline/Core/Acceptable THPS administered
for 96 hours at 0,18.1, 30.2, 50.4, 84, and 140 mg/L
10 fish/treatment
level Purity: 75% 96 hour LC 50 = 94 mg/L
The test
material is slightly toxic
to Rainbow
Trout
850.1075: Fish acute toxicity test (Sheepshead Minnow) MRID#: 442796-02 Boeri et al. (1995) Actue toxicity of THPS to the Sheepshead Minnow under flow-through
conditions Core/Acceptable/Guideline THPS administered for 96 hours at 0, 13, 22, 36, 60, and 100 mg/L 20 replicates of 20
fish/treatment level Purity 76.8 % LC 50 = 72 ppm;
NOEAL = 41

ppm Slightly toxic

850.2100:
Avian Oral Toxicity test (Mallard Duck) MRID#: 422363-21 Roberts, N (1987) THPS: acute oral toxicity (LD 50 )of DP 435 to the
Mallard Duck Acceptable-guideline/Core THPS administered at 0, 70, 126, 227, 408 and 735 mg/Kg
5 Mallard
Duck/sex/dose Purity 75% LD 50 = 324 mg/kg;
NOEAL =70 mg/Kg
THPS is moderately
toxic to
Mallard Ducklings
850.2200: Avian acute toxicity test (Mallard duck) MRID#: 422363-22: Roberts, N (1987);THPS: dietary toxicity (LC 50 ) of
DP 435 to the Mallard Duck Acceptable-guideline/Core THPS administered at 0, 300, 570, 1083, 2058, 3910, and 7428 ppm
10 ducks/dose Purity: 75% LC 50 = 1313 ppm; NOEAC
not achieved
due to all dose
levels had
reduced food consumption
and decreased body weight gains THPS may be
classified as slightly toxic

10to Mallard
Ducks
850.2200: Avian acute dietary toxicity test (Bobwhite Quail) MRID#: 422363-23 Roberts, N (1987) THPS dietary toxicity (LC 50 ) of DP 435 to the Bob white Quail Acceptable-guideline/Core THPS administered at 162.5, 325, 650, 1300, 2600, 5200

ppm 10 chicks/test level Purity: 75% Reduced body weight gain
THPS is slightly toxic
to Bobwhite Quail

Ecotoxicity Conclusions

THPS have been determined to show modera te acute toxicity to estuarine/marine organisms like Mysid Shrimp as well as to bivalves. THPS shows slight to moderate acute toxicity to Bluegill Sunfish and Rai nbow Trout while it is only slightly toxic to Sheephead Minnow. For Avian Toxicity Testin g, it shows moderate oral toxicity to Mallard Duck while only slight dietary acute toxicity is obse rved with Mallard Duck and Bobwhite Quail. As the uses of this pestic ide are in the outdoors, a number ecotoxicity are triggered as listed below.

Table 5 provides the toxicity categories for terrestrial and aquatic organisms based on end points:
Table 5 Ecotoxicty Categories
Birds Mammals LD50(mg/kg) LD50(ppm) Category Aquatic organisms LC50 (ppm); EC50(ppm)
<10 < 50 Very highly toxic < 0.1
10-50 50-500 Highly toxic 0.1-1
51-500 501-1000 Moderately toxic > 1-10
501-2000 1001-5000 Slightly toxic >10-100
>2000 >5000 Practically non-toxic > 100

Ecotoxicity Data Gaps: The Agency anticipates requiring th e following ecotoxicity studies:

1. 850.1010: Acute Freshwater Invertebrates Toxicity 2. 850.1300/ 850.1350: Acute Invertebrate Life-Cycle 3. 850.1400: Fish Early Life Cycle 4. 850.4400: Aquatic Plant Growth (Aquatic Va scular Plant), tier II-dose Response 5. 850.5400: Aquatic growth, Tier II, four species.

Endangered Species Determination:

The Agency has not conducted an ecological risk assessment that supports a complete endangered species determination. The ecolo gical risk assessment planned during the

11registration review will allow the Agency to determine whether THPS’s use has “no effect” or “may affect” federally listed threat ened or endangered sp ecies (listed species) or their designed critical habitats. When an assessment concludes that a pesticide’s use “may affect” a listed species or its designate d critical habitat, the Agency will consult
with the US Fish and Wildlife Service and/or National Marine Fisheries Services as appropriate

BIBLIOGRAPHY FOR: PRODUCT CHEM ISTRY, ENVIRONMENTAL FATE AND TRANSPORT, AND ECO-EFFECTS

1. ( Li,Y, saho Shuanggxi, Shi, Kaiqi, and Jaing Lan) in the Journal of the Society of Leather Technologists and Chemists: July/August 2008: 92(4), pp 167-169.
2. MRID: 466599-02: P/chem. properties of THPS.
3. MRID#: 42236334 J. O’Connor: Tetrakis(hydrox ymethyl)Phosphonium Sulfate (THPS): Determination of the Hydrolysis as a Function of pH: Lab Project #: 91/0737, prepared by Life Science Research Ltd; pp 78
4. August 2009 , Kahli Zhao, Jie Wen, Tingyue Gu, Ardjan Kopliku, and Ivan Cruz Materials Performance, pp 62-66
5. EPI Suite, version 4.1
6. RASSB Memo from Allen Va ughan to Norm Cook: (2002)
7. RASSB Memo from Rick Petr ie to Norm Cook: (2002)
8. Product Safety Assessment AQUCAR THPS 75 Water Treatment Microbiocide: http://www.dow.com/homepage/term.asp . Created: July 26, 2010

12APPENDIX

DATA JUSTIFICATIONS FOR THPS

ECOTOXICITY

Guideline Number: 850.5400 Study Title: Algal toxicity (Tier II) Rationale for Requiring the Data As part of a Tier I risk assessment, one indicator pl ant species is tested for phytotoxicity. This study
would allow the Agency to categorize THPS as toxic or non- toxic to plants. If toxic, additional higher tier plant tests would be needed. An endangered species assessment for endangered or threatened plants is not possible without this study. Practical Utility of the Data
1. How will the data be used? This study would be used to evaluate the toxicity of THPS to non-target plants in terrestrial and aquatic ecosystems. 2. How could the data impact th e Agency’s future decision-making? Adverse effects to non-target plants in terrestrial and aquatic ecosystems may result in mitigation to protect species at risk. Mitigation might include redu ced label dosages, neutrali zation of effluents prior to discharge into water, restrictions on use in sensitive ecosystems or where endangered species are present, or other mitigation measures. 3. What is triggering the need for this data? Increased concern from state regulators and the public to evaluate impacts on WWTP operations, endangered species, and persistence in the environment, sin ce initial registration, have triggered the need for this study. Green algae are critical to ecosy stem health and productivity.

13Guideline Number: 850.1075 Data Requirement: Acute Fish Toxicity (estuarine/marine) Rationale for Requiring the Data Sport fishing and commercial fishing have a high impact on the United States economy. The acute toxicity tests with estuarine/marine fish are desi gned to measure mortality during short-term (96-h) aquatic exposure to a range of concentrations of the pesticide in water. The preferred test species is
Atlantic silverside ( Menidia menidia ) for salt water. Practical Utility of the Data
1. How will the data be used? Data would be used to determine concentration-response curves and calculate LC50's (with 95% confidence intervals) for 24, 48, 72, and 96 h. Additionally, a NOEC for 96 h is reported. The
results from these studies may also provide information for a concentration-selection rationale for fish early-life stage study (OPPTS 850.1400) and the fish life cycle study (OPPTS 850.1500).
2. How could the data affect the risk assessment? There are many estuarine/marine fish species that are listed as threaten ed and endangered in the United States. Although the Atlantic silverside is the preferred species, the sheepshead minnow is considered a surrogate species to represent all mari ne/estuarine fish species in the risk assessment process. As part of the acute risk assessment for aquatic animals, the lowest EC50 or LC50 for
estuarine/marine fish is used in the RQ equation. An acute RQ > 0. 5 would indicate an acute LOC, defined as the potential for acute risk to non-target organisms which may warrant regulatory action in addition to restricted use classification. An acute RQ > 0.1 would result in an acute restricted use LOC, defined as the potential for acute risk to non-target organisms, which may be mitigated through restricted use classification. An acute RQ > 0.05 would fall under the LOC for acute endangered species. 3. What is triggering the need for this data? Data are needed in order to conduct an ecological risk assessment for the proposed use of THPS and determine the acute toxicity of THPS to estuarine/marine fish.

Guideline Number: 850.1400 Study Title: Freshwater Fish Early Life Stage us ing Rainbow Trout, Fathead Minnow, Zebra Fish,
or Rice Fish Rationale for Requiring the Data Fish early-life stage study is less expensive to conduct than the full life cycle study. Fish early-life stage study gives us some indications if the pesticid e is toxic to fish reproduction and survival. In the fish early-life stage study, fertilized eggs are placed in test chambers and exposed to the pesticide in
water at least until all the control fish are free-feed ing. Lethal and sublethal effects are assessed and compared with control values to determine the LOEC and the NOEC.

Practical Utility of the Data 1. What is the value of the study? Data are needed in order to conduct an ecological risk assessment for the proposed use of THPS and
determine the effects of THPS on fish development and survival during early life stages.

2. How will the data be used? The data are used to determine embryo hatch rate, time to hatch, time to swim-up, growth (length and weight), and any clinical or pathology findings

3. How could the data affect the risk assessment? As part of the chronic risk assessment for aquatic animals, the lowest NOEC for estuarine/marine fish

14is used in the RQ equation. A chronic LOC is defined by an RQ > 1, and would indicate that there is the potential for chronic risk that may warrant regulatory action and that endangered species may potentially be affected through chronic exposure.

Guideline Number: 850.1350 Study Title: Marine Aquatic Invertebrate Mysidopsis bahia Rationale for Requiring the Data

Invertebrates serve as food for fish, birds, crustacean s, and even whales. The protection of non-target invertebrates is essential to the food chain in any healthy ecosystem. The value in the Daphnid (850.1300) and Mysid (850.1350) chronic toxicity tests are that they provide information on the effects of pesticides on mortality, growth, and reproduction over a longer term (21 days for Daphnids and 28 days for Mysids) compared to acute studies. Data are obtained from th e first generation (G1) and the second generation (G2), thus allowing examination of the complete invertebrate life cycle for toxicity. Practical Utility of the Data
1. What is the value of the study? Data are needed in order to conduct an ecological risk assessment for the use of THPS to determine the chronic toxicity of THPS to freshwater and marine invertebrates using life-cycle studies.
2. How will the data be used? Data would be used to calculate LC50’s for mortality, EC50’s for growth, a NOAEC, and a MATC (maximum acceptable toxicant concentration). The da ta would allow the Agency to determine chronic effects, including effects on reproductive success and gr owth, to freshwater and marine invertebrates from water column exposure to THPS

. 3. How could the data affect the risk assessment? Because acute toxicity data alone are not a reliable indicat or of chronic toxicity, chronic toxicity data are also required. The Agency cannot make the assumption that a chemical is not chronically toxic at much lower
concentrations than some ratio of the LC50 value woul d suggest. The results would be used to determine the likelihood that the chronic risks can potentially imp act aquatic communities, either by direct effects on invertebrates or by indirect effects on organisms which feed on them. Daphnia magna (for fresh water) and Mysidopsis bahia (for salt water) are used to represent all invert ebrate species living in the water column in the risk assessment process. Additionall y, the use of the most sensitive sp ecies ensures the protection of other species within that taxon. As part of the chronic risk assessment for aquatic animals, the lowest NOAEC for estuarine/marine invertebrates is used in the RQ equa tion. A chronic LOC is defined by an RQ > 1, and would indicate that there is the potential for chroni c risk that may warrant regulatory action and that endangered species may potentially be a ffected through chronic exposure.

Guideline Number: 850.4400 Study Title: Aquatic Macrophyte Study using Lemna gibba Rationale for Requiring the Data Aquatic plants are essential components of any healthy ecosystem. Plants provide food, shelter, and oxygen to animal species. Lemna represents floating aquatic macrophytes. As part of a Tier I risk assessment, one freshwater aquatic plant indicator species, ( Lemna gibba or L. minor ), is exposed to a range of concentrations of THPS in fresh water to measure phytotoxicity.

Practical Utility of the Data

1. What is the value of the study?

15Data are needed in order to conduct an ecological risk assessment for the uses of THPS and determine its effects on aquatic plants because they are critical to ecosystem health and productivity.
2. How will the data be used? This study would be used to evaluate the toxicity of THPS to non-target plants in aquatic ecosystems. Data from these studies would be used to plot concentration response curves for total frond number, growth rate (as number of fronds per day), and mortality (percentage of dead fronds to total number of fronds). EC05s, EC50s, and EC90s would be calculated from the curves. Tier II (definitive) testing is not required if Tier I testing results in an EC50 greater than 1000 mg/L or less than the analytical detection limit. Tier II tests may also include endpoints such as measurements of chlorophyll pigments, biomass, and more detailed observations of frond appearance (i.e., decrease in size, necrosis, chlorosis, or sinking).

3. How could the data affect the risk assessment? Lemna spp. are used to represent all aquatic plants in the risk assessment process. Adverse effects to non-target plants in aquatic ecosystems may result in mitigation to protect species at risk. Mitigation might include reduced label dosages, neutralizatio n of effluents prior to discharge into water, restrictions on use in sensitive ecosystems or where endangered species are present, or other mitigation measures. Aquatic plants may be affected when THPS is used as an antimicrobial. If EPA is unable to evaluate the potential risks to aquatic plants associated with the uses of THPS, these risks must be presumed. As part of the risk assessment for aquatic vascular plants, the lowest EC50 is used in the RQ equation. The LOC for endangered and non- endangered plants is defined as a RQ > 1.

16Guideline Number: 850.5400 Study Title: Aquatic Plants (4) using Selenastrum capricornutum (green algae), Anabaena flos-aquae (blue-green cyanobacteria), Navicula pelliculosa (freshwater diatom), and Skeletonema costatum (marine diatom) Rationale for Requiring the Data

As part of a Tier I risk assessment, one indicator pl ant species is tested for phytotoxicity. This study
would allow the Agency to categorize THPS as toxic or non- toxic to plants. If toxic, additional higher tier plant tests would be needed. An endangered species assessment for endangered or threatened plants is not possible without this study. Practical Utility of the Data

1. What is the value of the study? Increased concern from state regulators and the public to evaluate impacts on WWTP operations, endangered species, and persistence in the environment, sin ce initial registration, have triggered the need for this study. Green algae are critical to ecosy stem health and productivity.
2. How will the data be used? This study would be used to evaluate the toxicity of THPS to non-target plants in terrestrial and aquatic ecosystems.

3. How could the data affect the risk assessment?

Adverse effects to non-target plants in terrestrial and aquatic ecosystems may result in mitigation to protect species at risk. Mitigation mi ght include reduced label dosages, ne utralization of ef fluents prior to discharge into water, restrictions on use in sensitive ecosystems or where endang ered species are present, or other mitigation measures.

Guideline Number: 850.1010 Study Title: Acute Aquatic Invertebrate Rationale for Requiring the Data

This study will allow the Agency to determine the toxicity of THPS to freshwater daphnids. An endangered species assessment for endangered or threatened freshwater daphnids is not possible without this study. Therefore, this study is required.

Practical Utility of the Data 1. How did the Agency make its re-reg istration decision without this data?

The Agency imposed risk mitigation through labeling changes as an interim measure.

2. How will the data be used?

The study will be used for hazard labeling in th e event a spill of manufacturing use product occurs. This study will be used to generate a freshwater inve rtebrate endpoint so that the Agency can evaluate the toxicity of m-Cresol to non-target and endange red/threatened freshwater daphnids in freshwater aquatic ecosystems.

173. How could the data impact the Agency’s future decision-making?

If the acute freshwater fish toxicity is 1.0 mg/L or less, the label must state: “This pesticide is toxic to fish.” A freshwater fish endpoint will allow the Ag ency to determine if endangered or threatened species are at risk or if freshwater fish are imp acted after residues pass through waste water treatment plants into surface waters. Mitigation might includ e reduced label dosages, neutralization of effluents prior to discharge into water, restrictions on u se in sensitive ecosystems or where endangered species are present, or other mitigation measures which require refined scientific assessments.

Guideline Number: 850.1300 Data Requirement: Aquatic invertebrate chronic NOAEC using Daphnia magna
Guideline Number: 850.1350 Data Requirement: Aquatic invertebra te chronic NOAEC using mysid shrimp Rationale for Requiring the Data Invertebrates serve as food for fish, birds, cr ustaceans, and even whales. The protection of nontarget invertebrates is essential to the food chai n in any healthy ecosystem. The value in the Daphnid (850.1300) and Mysid (850.1350) chronic toxicity tests are that they provide information on the effects of pesticides on mortality, growth, and reproduction over a longer term (21 days for Daphnids and 28 days for Mysids) compared to acute studies. Data are obtained from the first generation (G1) and the second generation (G2), thus allowing examination of the complete invertebrate life cycle for toxicity. Practical Utility of the Data
1. How will the data be used?

Data would be used to calculat e LC50's for mortality, EC50's fo r growth, a NOEC, and a MATC (maximum acceptable toxicant concentration). The data would allow the Agency to determine chronic effects, including effects on reproductiv e success and growth, to freshwater and marine
invertebrates from water column exposure to THPS.

2. How could the data affect the risk assessment? Because acute toxicity data alone are not a reliable indicator of chronic t oxicity, chronic toxicity data are also required. The Agency cannot make the assumption that a chemical is not chronically toxic at much lower concentrations than some ratio of the LC50 value would suggest. The results would be used to determine the likelihood that the chronic risks can potentially impact aquatic communities, either by direct effects on inverteb rates or by indirect effects on organisms which feed on them. Daphnia magna (for fresh water) and Mysidopsis bahia (for salt water) are used to represent all invertebrate species living in the water column in the risk assessment process. Additionally, the use of the most sensitive species ensures the protection of other species within that taxon. As part of the chronic risk assessme nt for aquatic animals, the lowest NOEC for estuarine/marine invertebrates is used in the RQ equation. A chronic LOC is defined by an RQ > 1, and would indicate that there is the potential for chronic risk that may wa rrant regulatory action and that endangered species may potentially be affected through chronic exposure. 3. What is triggering the need for this data? Data are needed in order to conduct an ecological ri sk assessment for the proposed use of THPS as a
wood preservative and determine the chronic toxicity of THPS to freshwater and marine invertebrates using life-cycle studies.

18PRODUCT CHEMISTRY

DATA JUSTIFICATIONS FOR THPS

Guideline Number: 830.7840xxxx Study Title: Solubility in Organic Solvents in g/100 Ml Rationale for Requiring the Data

Pesticides, at use level are not necessarily soluble in wate r, and hence it is important for the agency to know the solubility in other solvents. The Agency has been asking this data for agricultural pesticides routinely. OECD also requires this data. This data will harmonize the data set for all major agencies Practical Utility of the Data What is the value of the study? It is part of the product chemistry data require ments (830 Series), and is needed to complete the database for product characteristics of THPS

2. How will the data be used? This data will help the Agency to ascertain that th is chemical is stable in some commonly available solvents, other than water. Also it will help the Agen cy to know that no unstable entities (dangerous or hazardous) are formed by this pesticide in organic solvents.

3. How could the data affect the risk assessment? The Agency would want to ascertain that risk st udies are conducted properly in the presence of the right solvent (the solvent used when the pesticide is applied). The data can then be used for risk assessments.

19ENVIRONMENTAL FATE AND TRANSPORT

DATA JUSTIFICATIONS

Guideline Number: 835.3110 Data Requirement: Ready Biodegradability Rationale for Requiring the Data The ready biodegradability study would enable the Agency to determine the likelihood that the antimicrobial pesticide of biodegrading in aquatic environments under aerobic conditions. Practical Utility of the Data

1. How would the data be used?
The results from the data would be used to determ ine the rate and extent of aerobic biodegradation
of THPS when it is releas ed into aquatic environments and would help establish if THPS is stable or
not stable under real environmental conditions.

2. How could the data affect the risk assessment? If the result shows low biodegradability then, THPS would occur in significant quantities in WWTP
effluents (water and biosolids) and in environmental co mpartments (e.g., surface waters) such that potential adverse effects to nontarget organisms, found in such environmental compartments, may

occur. 3. What is triggering the need for this data?
Data are needed to conduct environmental fate assessment and to determine the ready biodegradability
of THPS

20Guideline Number: 835.2240 Data Requirement: Photodegradation in water Rationale for Requiring the Data Biocides introduced into aqueous systems in the environment can undergo photolytic transformation by sunlight. Results from the photolysis study will indicate the stability and persistence of THPS and potential degrades in an aquatic environmen t when exposed to sunlight. For outdoor wood preservative uses THPS can reach surface water through direct contact or discharge to WWTPs. THPS may also reach surface water or groundwater through run-off or leaching processes. The Agency will evaluate the potential risks of concern. Practical Utility of the Data
1. How will the data be used? The data would establish the significance of chemical photolysis as a route for degradation and identify, if possible, the photolytic degradation pr oducts formed that may adversely affect non-target organisms and may contaminate water and food sour ce of aquatic organisms. The data would alsohelp establish the photolytic halflife of THPS and possibly degrades, and assi st in developing a degradation pathway.

2. How could the data affect the risk assessment? The results of photolysis data would indicate if THPS is persistent or if it degrades into degradation products that may adversely affect non-target organisms and may contaminate their food. The results of the photolysis data would expand the understanding of the results of the hydrolysis data since environmental aquatic conditions usually involve exposure to sunlight. 3. What is triggering the need for this data? Aqueous photo-degradation data is needed to conduct the fate assessment to support indoor and
outdoor wood preservative uses for THPS.

21Guideline Number: 835.4300 Data Requirement: Aerobic aquatic metabolism Rationale for Requiring the Data The purpose of an aerobic aquatic metabolism study is to determine the nature and extent of
microbial degradation under aerobic conditions in water/ sediment systems, during the period of dispersal of the biocide throughout the aquatic envi ronment, and to characterize the formation and decline of degrades. This information will determine the persistence and concentrations of THPS and potential degrades over time in representative aerobic water/sediment systems. The results will indicate the potential for THPS to contaminate the aquatic environment that may come in contact with the preserved wood since biocide residues may be taken up by irrigated crops and passed on to other parts of the aquatic food web. The Agency will evaluate the potential risks of concern. Practical Utility of the Data

1. How would the data be used? The data would establish the significance of aerobic aquatic microbial degradation of THPS as a route for degradation and identify, if possible, th e degradation products formed that may adversely affect non-target organisms and may contaminate water and food sources of aquatic organisms. The data would also help establish the aerobic aquatic microbial half-life of THPS in water/sediment systems, and possibly it's degrades, and assist in developing a degradation pathway.

2. How could the data affect the risk assessment? The results would indicate the nature and extent of formation and decline under aerobic aquatic conditions of THPS and its degradates that may be taken up by irrigated crops and passed on to other parts of the aquatic food web, and would facilitate assessment of potential disposal problems. The study helps to determine the degradation rate (half-life) of THPS in the presence of microorganisms in different natural water/sediment systems and determines what metabolites are formed under aerobic (oxygen-rich) conditions in the laboratory. 3. What is triggering the need for this data? Aerobic aquatic metabolism data is needed to conduct the fate assessment to support indoor and
outdoor wood preservative uses for THPS.

22Guideline Number: 835.4400 Data Requirement: Anaero bic aquatic metabolism Rationale for Requiring the Data The purpose of an anaerobic aquatic metabolism study is to determine the nature and extent of microbial degradation under anaerobic conditions in water/sediment systems (hydrosoils), during the period of dispersal of the biocide throughout the aquatic environment, and to characterize the formation and decline of degradates. This in formation will determine the persistence and concentrations of THPS and potential degradates over time in representative anaerobic water/sediment systems. The results will indicate the potential for THPS to contaminate the aquatic environment that may come in contact with the preserved wood since biocide residues may be taken up by irrigated crops and passed on to other parts of the aquatic food web. Additionally, anaerobic conditions are more likely to prevail where biocid es are found in aquatic environments than in strictly terrestrial environments. The Agency will evaluate the potential risks of concern. Practical Utility of the Data

1. How would the data be used? The data would establish the significance of anaerobic aquatic microbial degradation of biobor as a route for degradation and identify, if possible, the degradation products formed that may adversely affect non-target organisms and may contaminate water and food sources of aquatic organisms. The data would also help establish the anaerobic aquatic microbial half-life of biobor in water/sediment systems, and possibly its degradates and, assist in developing a degradation pathway.

2. How could the data affect the risk assessment? The results would indicate the nature and extent of formation and decline under anaerobic aquatic conditions of THPS and its degradates that may be taken up by irrigated crops and passed on to other parts of the aquatic food web, and would fa cilitate assessment of potential disposal problems. The study helps to determine the degradation ra te (half-life) of THPS in the presence of microorganisms in different natural water/sediment systems and determines what metabolites are formed under anaerobic (oxygen-poor) conditions in the laboratory. 3. What is triggering the need for this data? Anaerobic aquatic metabolism data is needed to conduct the fate assessment to support indoor and
outdoor wood preservative uses for THPS.

23Guideline Number: 835.1240 Data Requirement: Leaching and adsorption/desorption Rationale for Requiring the Data
Biocides introduced into th e soil have the potential to leach through the soil profile or transport to and dispersion in the aquatic environment. This movement of biocide residues may cause contamination of food, result in loss of usable land and water resource s to man due to contamination of groundwater supplies, or cause habitat loss to wildlife. Therefore, laboratory studies are required to predict: (1) the leaching potential of biocides and degradates through the soil profile at terrestrial sites; and (2) the movement of biocides and degrad ates to and dispersion in aquatic sites. Results from the soil column leaching study will provide information on the soil mobility of biobor and its transformation products and thei r potential to reach aquatic en vironments. For outdoor wood preservative uses, biobor can reach surface water through direct contact or discharge to WWTPs. Biobor may also reach surface wa ter or groundwater through run-o ff or leaching processes. The Agency will evaluate the potential risks of concern. Practical Utility of the Data
1. How will the data be used? Adsorption/desorption coefficients (Kd) for THPS would be obtained for the representative soils or aquatic sediments tested; however, partition coeffi cient estimates from soil-column leaching studies have substantially less precision than those estimated using batch equilibrium studies, which are considered to be a much more direct measure of the parameter. The Kd values, along with the solubility data, would establish the extent of de pth of leaching for THPS and its transformation products through the soil profile of different soil types representative of typical use sites. Since aquatic/aquatic impact uses are proposed for THPS, the data would also establish the extent of depth of leaching for THPS and its transformation products in sedi ments. The Kd values are used in simulation modeling for registration review and new use registrations.

2. How could the data affect the risk assessment? The results would indicate if THPS and its degradates leach through the soil/sediment profile, causing possible contamination of food, loss of usable land and water resources to man due to contamination of groundwater supplies, or loss of habitat to wildlife. The results could yield an improved confidence in the results of drinking water and ecological risk assessments. 3. What is triggering the need for this data? Soil column leaching data is needed to conduct th e fate assessment to support indoor and outdoor
wood preservative uses for THPS.

2425 Guideline Number: 835.1230 Data Requirement: Sediment and soil adsorption/desorption Rationale for Requiring the Data
Biocides introduced into th e soil have the potential to leach through the soil profile or transport to and dispersion in the aquatic environment. This movement of biocide residues may cause contamination of food, result in loss of usable land and water resources to man due to contamination of groundwater supplies, or cause habitat loss to wi ldlife. Therefore, laboratory studies are required to predict: (1) the leaching potential of biocides and degradates through the soil profile at terrestrial sites; and (2) the movement of biocides and degradates and dispersion in aquatic sites. Results from the adsorption/desorption study will provide info rmation on the soil mobility of THPS and its transformation products and their potential to reach aquatic environments. For outdoor wood preservative uses, THPS can reach surface water through direct contact or discharge to WWTPs. THPS may also reach su rface water or groundwater through ru n-off or leaching processes. The Agency will evaluate the potential risks of concern. Practical Utility of the Data
1. How will the data be used? The data would establish the significance of leachin g as a route for THPS and/or its degradates to disperse and potentially reach aquatic environm ents. The study would help define the leaching behavior of THPS and/or its degradates by char acterizing their adsorption/ desorption coefficients (Kd) in representative soils and aquatic sediments. If the Freundlich equation is used, examples of calculations for 1/n and K values would also be provided. The adsorption/desorption coefficients calculated from a batch equilibrium study are used along with solubility data to predict the extent of depth of biocide leaching in the different soil t ypes representative of typical use sites. Since aquatic/aquatic impact uses are proposed for THPS, the data would also establish the extent of depth of leaching for THPS and its degradates in se diments. The Kd values are used in simulation modeling for registration review and new use registrations.

2. How could the data affect the risk assessment? The results would indicate if THPS and its degr adates have the potentia l to leach through the soil/sediment profile, causing possible contamination of food, loss of usable land and water resources to man due to contamination of groundwater supplies, or loss of habitat to wildlife. The results could yield an improved confidence in the results of drinking water and ecological risk

assessments. 3. What is triggering the need for this data? Adsorption/ desorption data is needed to conduct the fate assessment to support indoor and outdoor
uses for THPS.