### 1 Summary of Meeting Between EPA Registration Review Antimicrobial Division Staf f

and Rhodia Inc. May 12, 2011

Participants: Eliza Blair, Chemical Review Manager for THPS, EPA Lance Wormell, EPA Antimicrobial Registration Revie w Team Leader Nathan Mottl, Toxicology, (EPA) Srinivas Gowda, Environmental Assessment, (EPA) Najm Shamim, Chemistry, (EPA) Timothy Dole, Human Health, (EPA) Timothy Leighton, Human Health, (EPA) Scott Boito, Rhodia Glenn Simon, Rhodia Annie Buard, Rhodia Cristina Griffin, Delta Analytical, Agent for Rhodi a On the telephone: Steve Groome, Rhodia Ian Bartlett, Rhodia Pauline Bingham, Rhodia

Attachments: Meeting Agenda Reports submitted by Rhodia but not included in E PA’s lists of studies reviewed Comments on THPS Chemistry

On 12 May 2011 Rhodia Inc. met with EPA to discuss the draft workplan for EPA registration review of Tetrakis (hydroxymethyl) phosphonium sul fate (THPS). Rhodia explained that Albright & Wilson (a company later acquired by Rhod ia) first registered THPS in the United States in 1995.

Rhodia provided information on the chemistry of THP S and specifically the relatively small amount of formaldehyde generated during use of the product (see attached handout entitled Comments on THPS Chemistry). Rhodia explained that THPS is the biocide and that the levels of THPS dwarf the formaldehyde levels. Formaldehyd e has its own uses. THPS is used in situations in which formaldehyde is not effective.

There was discussion regarding the appropriate term inology for formaldehyde in THPS as THPS is not a formaldehyde release agent, but rathe r formaldehyde is a minor byproduct. This issue is new to EPA as up to now, they have worked with products in which formaldehyde is the active ingredient.

EPA discussed information needed in order to be abl e to conduct the risk assessment including studies on THPS in aerobic conditions and biodegrad ation studies. Rhodia indicated that it has a hydrolytic stability study (aerobic conditions) a nd radiolabeled studies that show biodegradation to CO 2 within 28 days supporting classification of THPS a s a readily biodegradable substance. Rhodia also discussed tha t in Europe measurements were conducted with regard to use of THPS in a pilot sca le sewage sludge system and no formaldehyde could be found.

EPA discussed formaldehyde in air and stated that t he Agency needs data in order to determine that the formaldehyde released into the air by THPS is below the level of concern. EPA explained use of a couple of different models to es timate air emissions. Rhodia discussed that

### 2

EPA’s workplan includes discussion of certain uses that Rhodia does not market. EPA indicated that deleting the paint use would negate the need to run the wall paint exposure model. EPA indicated Rhodia should use EPA’s Indoo r Air Quality model (called IAQX) to determine whether THPS use would exceed EPA’s level of concern which currently is 100 ppb for formaldehyde. EPA agreed to send the link for the model.

With regard to open versus closed loading, EPA stat ed it would review dermal exposure data from the Antimicrobial Exposure Assessment Task For ce (AEATF), as well as air data. Rhodia noted that it is a member of the AEATF. In additio n, Rhodia explained that it had conducted a THPS dermal penetration study for Canada which show ed very limited dermal penetration.

Rhodia noted that some use sites listed in the work plan appear to be an error and are not indicated on the product labels- in particular use in leather preservation, wood preservation, surface disinfection and paint. As there are no cl aims on the Rhodia labels that could be interpreted as directions for leather preservation, wood preservation or surface disinfection, EPA agreed it would evaluate whether THPS antimicrobial uses actually include leather preservation, wood preservation and surface disinfection. Rhodia also does not market THPS for use in paints, as it does not work, and understands that n o customers will be using THPS in paint. Rhodia noted that the solution and emulsion use tex t may be interpreted as allowing use in paints, and offered to improve the labeling descrip tion to note that THPS is not to be used in paint, to make this explicit.

Rhodia discussed the handout entitled “Reports subm itted by Rhodia but not included in EPA’s lists of studies reviewed” (attached). EPA agreed t o review the list and determine whether the studies that meet current guidelines should have be en considered. Rhodia also asked as the original registrant for THPS, why other chemistry M RID numbers had been referenced as the basis for EPA’s chemistry profile of THPS. EPA ask ed Rhodia to provide information on this and determine whether there were any differences in data.

With regard to data, EPA indicated its preference t hat Rhodia submit additional data that would aid the risk assessment during the Data Call-In per iod, prior to EPA conducting the risk assessment. EPA noted there is a mechanism for EPA to request those studies so all data compensation options would be preserved.

EPA listed the next steps as:

- EPA will send Rhodia the link for the Indoor Air Q uality model.

- EPA will review whether some of the use sites were erroneously included in its work plan and whether they may be removed. If so, EPA will n ote this in the final work plan.

- Rhodia will submit label amendments to remove pain t uses from its labeling. Rhodia will provide information on the chemistry MRID numbers i f there are differences

- Rhodia to provide written comments on draft work p lan and EPA will respond to those comments.

- EPA will be posting the meeting materials, includi ng the participant list, in the public docket. Rhodia is to provide EPA with a redacted v ersion of the handouts.

- EPA will review the sheet listing the studies that were not included in the draft work plan.

- EPA will review terminology in the workplan for TH PS to avoid confusion with conventional formaldehyde release agents (FRA’s) th at function by releasing formaldehyde as the active substance. In THPS, THPS itself is the active substance and formaldehyde would only be unintentionally formed a t very low levels as a potential byproduct from degradation processes.Attachment


## AGENDA for Meeting Rhodia, Inc. and EPA THPS Registration Review 12 May 2011 from 10am – Noon

Purpose: To discuss EPA’s THPS Registration Review Scoping Documents Chemistry/Environmental Fate/Ecotoxicity of 1/24/11 ; Summary of Human Health Effects data of 2/18/11; and THPS Summary Document March 2011

• Introductions

• Rhodia presentation and discussion

⋅ Chemistry of THPS, information on why THPS is not a formaldehyde release agent

⋅ Current uses in accordance with EPA approved Rhodi a labeling, uses not part of current Rhodia labeling

⋅ Current Rhodia sales by market (Confidential Busin ess Information)

• Discussion and questions

⋅ Rhodia is prepared to amend labeling to specify “n ot for use in paint, leather preservatives, as a wood preservative, or as a surf ace disinfectant.” Rhodia believes that this should negate the need for the s tudies listed below and requests EPA’s input on this list:

o 90 day inhalation study

o Residential exposure data requirements

o Indoor/outdoor inhalation exposure studies

o Dermal exposure (outdoor and indoor)

o Leaching and adsorption/desorption

⋅ The attached document lists Environmental Effects studies previously submitted by Rhodia but not included in EPA’s summa ry of data: Rhodia requests to know whether these studies were conside red by EPA but not included purposely, or were not considered during t he review and, if so, why.

⋅ EPA’s Chemistry scoping document Table #4, page 6, lists MRID #466599-02 as the basis for the physical and chemical properti es table. Rhodia requests information on why this study was used rather than that of the original registrant and, in general, when multiple studies e xist to satisfy a data requirement, how EPA determines which study to cite and use?

⋅ If Rhodia deletes the label uses as discussed abov e, is it correct to assume that EPA will specify in the Data Call-In that cert ain of the studies are only required for products which include (or have not ex plicitly prohibited) those specific uses?

• Conclusion/next stepsAttachment

Reports submitted by Rhodia but not included in EPA ’s lists of studies reviewed

Guideline No. Name of

Study MRID No. Full Study Title Date of EPA Submission

850.1010 Aquatic

invertebrate acute toxicity test, freshwater daphnids 42236326 Jenkins, W. (1989) Tetrakishydroxymethyl Phosphonium Sulphate (THPS): Acute Toxicity to Daphnia Magna 2/14/1992

42236332 Jenkins, C. (1991) Tris (Hydroxymethyl)

Phosphine Oxide (THPO): Acute Toxicity to Daphnia Magna 2/14/1992

44135408 Torp, U.; McWilliams, P. (1994)

Determination of Acute Lethal Toxicity to Acartia tonsa : Tolcide PS75 10/16/1996

44135409 Torp, U.; McWilliams, P. (1994)

Determination of Acute Lethal Toxicity to Acartia tonsa : Tolcide PS355A 10/16/1996

850.1045 Shrimp

acute toxicity test 44135405 Douglas, M.; Pell, I. (1986) The Acute Toxicity of DP 435 to Brown Shrimp ( Crangon crangon ) 10/16/1996

850.1075 / 72-1,3 Fish acute

toxicity test, freshwater and marine 42236329 Cooney, J. (1991) Tetrakis(Hydroxymethyl)Phosphonium Sulfate (THPS): Static-Renewal Acute Toxicity Test of THPS to Sheepshead Minnows ( Cyprindon variegatus ) 2/14/1992

42236331 Jenkins, W. (1991) TRIS (Hydroxymethyl)

Phosphine Oxide (THPO): Acute Toxicity to Rainbow Trout 2/14/1992

44135404 Douglas, M.; Handley, J. (1989) The Acute

Toxicity of DP435 to Juvenile Plaice ( Pleuronectes platessa ) 10/16/1996

850.1300 Daphnid

chronic toxicity 42236328 Jenkins, W. (1990) Tetrakis(Hydroxymethyl) Phosphodium Sulfate (THPS): 21 Day Juvenile Production Test Under Semistatic Conditions 2/14/1992

850.1740 Whole

sediment acute toxicity invertebrate marine 44135406 Roddie, B. (1994) Assessment of the Sediment-Phase Toxicity of Tolcide PS 75 to the Sediment-Dwelling Amphipod Corophium volutator 10/16/1996

44135407 Roddie, B. (1994) Assessment of the

Sediment-Phase Toxicity of Tolcide PS355A to the Sediment-Dwelling Amphipod Corophium volutator 10/16/1996

850.5400 Algal toxicity 42236327 Jenkins, W. (1989) Tetrakis(hydroxymethyl)Phosphonium Sulphate (THPS): Determination of its EC50 to Selenastrum capricornutumUnder NonAxenic Conditions 2/14/1992

44135410 Hushagen, H.; McWilliams, P. (1994)

Marine Algal Growth Inhibition Test with Skeletonema costatum : Tolcide PS 75 10/16/1996

44135411 Hushagen, H.; McWilliams, P. (1994)

Marine Algal Growth Inhibition Test with Skeletonema costatum : Tolcide PS355A 10/16/1996Attachment

EPA Case # 5034 Docket Number: EPA -HQ-OPP-2011-0067 THPS (CAS: 55566-30-8)

Rhodia 12 May 2011 

## Comments on THPS Chemistry

Tolcide® PS75 is a 75% solution of THPS in water. T he manufacturing concentrate and all end use products are stable. The formaldehyde conce ntration in the commercial product is low and is closely controlled in the manufacturing process.

THPS is always used in water. When THPS concentrate is diluted in water to ppm levels, as it is when used as a biocide, it will begin to hydr olyze in the presence of even the smallest concentrations of dissolved oxygen.

THPS THPO Formaldehyde Sulfuric acid



### • When THPS is used as a biocide, THPO is the main d egradant.

• THPO is not a biocide and it was found not to have adverse effects on aquatic organisms tested (invertebrates, benthic organisms, fish and algae from freshwater and seawater).

• THPO will undergo complete mineralization to inorg anic phosphate, carbon dioxide, and water.

• THPO is not persistent in the environment.

• When THPS reacts to form THPO the stoichiometry is as follows:

1 mole THPS → 2 moles THPO + 2 moles formaldehyde + 1 moles sulf uric acid

406 g THPS → 60 g formaldehyde

• If the dose level of THPS is 10 ppm, as in our Ind ustrial Fresh Water Systems application, it will produce only 1.5 ppm of formal dehyde in solution.

• In the case of (hypothetical) complete degradation over 28 days, 1 mole of THPS would produce 8 moles of formaldehyde.

• This means 406 g of THPS would produce 240 g forma ldehyde.

• A dose of 10 ppm THPS would produce 5.9 ppm formal dehyde in water.

• Formaldehyde is very soluble in water and the smal l amount present is not expected to be released into the air.

1 HOH 2 C P + CH 2 OH SO 4 2

- 2 HOCH 2 P CH 2 OH + 2HCHO + H 2 SO 4 2

-

2 CH 2 OH

O CH 2 OH CH 2 OH

O 2Attachment

EPA Case # 5034 Docket Number: EPA -HQ-OPP-2011-0067 THPS (CAS: 55566-30-8)

Rhodia 12 May 2011 

### • Formaldehyde release agents (FRAs) release formald ehyde and their efficacy is comparable to that of formaldehyde.

• Their purpose is to produce formaldehyde in-situ to avoid handling of formaldehyde, or to provide slow delivery of formaldehyde

• The THPS molecule is itself the active biocidal ag ent. In contrast to FRAs, the mode of action and effectiveness of THPS are not dependent upon release of formaldehyde.

• THPS is biocidally more effective than formaldehyd e.

• THPS is faster acting than formaldehyde.

• THPS is effective against ‘formaldehyde-resistant’ bacteria.

• Formaldehyde is deactivated by hydrogen sulfide, w hereas THPS is not.

• 

### In oilfield applications, THPS is effective in sour systems whereas formaldehyde is not.

2