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Summary of Meeting Between 

EPA Registration Review Antimicrobial Division Staff 

and Rhodia Inc. 

May 12, 2011 

Participants: 

Eliza Blair, Chemical Review Manager for THPS, EPA 

Lance Wormell, EPA Antimicrobial Registration Review 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 Rhodia 

On the telephone: 

Steve Groome, Rhodia 

Ian Bartlett, Rhodia 

Pauline Bingham, Rhodia 

Attachments: Meeting Agenda 

 Reports submitted by Rhodia but not included in EPA’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 sulfate (THPS). Rhodia explained that

Albright & Wilson (a company later acquired by Rhodia) first registered THPS in the United 

States in 1995.

Rhodia provided information on the chemistry of THPS 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. Formaldehyde has its own uses. THPS is used in 

situations in which formaldehyde is not effective. 

There was discussion regarding the appropriate terminology for formaldehyde in THPS as 

THPS is not a formaldehyde release agent, but rather 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 able to conduct the risk assessment including 

studies on THPS in aerobic conditions and biodegradation studies. Rhodia indicated that it has 

a hydrolytic stability study (aerobic conditions) and radiolabeled studies that show 

biodegradation to CO2 within 28 days supporting classification of THPS as a readily 

biodegradable substance. Rhodia also discussed that in Europe measurements were 

conducted with regard to use of THPS in a pilot scale sewage sludge system and no 

formaldehyde could be found. 

EPA discussed formaldehyde in air and stated that the 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 estimate air emissions. Rhodia discussed that 
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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 Indoor 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 stated it would review dermal exposure data 

from the Antimicrobial Exposure Assessment Task Force (AEATF), as well as air data. Rhodia 

noted that it is a member of the AEATF. In addition, Rhodia explained that it had conducted a 

THPS dermal penetration study for Canada which showed very limited dermal penetration. 

Rhodia noted that some use sites listed in the workplan 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 claims 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 no customers will be using THPS in paint. 

Rhodia noted that the solution and emulsion use text may be interpreted as allowing use in 

paints, and offered to improve the labeling description to note that THPS is not to be used in 

paint, to make this explicit. 

Rhodia discussed the handout entitled “Reports submitted by Rhodia but not included in EPA’s 

lists of studies reviewed” (attached). EPA agreed to review the list and determine whether the 

studies that meet current guidelines should have been considered. Rhodia also asked as the 

original registrant for THPS, why other chemistry MRID numbers had been referenced as the 

basis for EPA’s chemistry profile of THPS. EPA asked Rhodia to provide information on this 

and determine whether there were any differences in data. 

With regard to data, EPA indicated its preference that Rhodia submit additional data that would 

aid the risk assessment during the Data Call-In period, 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 Quality 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 note this in the final work plan. 

- Rhodia will submit label amendments to remove paint uses from its labeling. Rhodia will 

provide information on the chemistry MRID numbers if there are differences 

- Rhodia to provide written comments on draft work plan and EPA will respond to those 

comments. 

- EPA will be posting the meeting materials, including the participant list, in the public 

docket. Rhodia is to provide EPA with a redacted version 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 THPS to avoid confusion with 

conventional formaldehyde release agents (FRA’s) that function by releasing 

formaldehyde as the active substance. In THPS, THPS itself is the active substance and 

formaldehyde would only be unintentionally formed at 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 Rhodia labeling, uses not 

part of current Rhodia labeling 

⋅ Current Rhodia sales by market (Confidential Business Information) 

• Discussion and questions 

⋅ Rhodia is prepared to amend labeling to specify “not for use in paint, leather 

preservatives, as a wood preservative, or as a surface disinfectant.” Rhodia 

believes that this should negate the need for the studies 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 summary of data: Rhodia 

requests to know whether these studies were considered by EPA but not 

included purposely, or were not considered during the 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 properties table. Rhodia requests 

information on why this study was used rather than that of the original 

registrant and, in general, when multiple studies exist to satisfy a data 

requirement, how EPA determines which study to cite and use? 

⋅ If Rhodia deletes the label uses as discussed above, is it correct to assume 

that EPA will specify in the Data Call-In that certain of the studies are only 

required for products which include (or have not explicitly prohibited) those 

specific uses? 

• Conclusion/next steps 
Attachment

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 capricornutum Under 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 

10/16/1996 
Attachment

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. The manufacturing concentrate and all 

end use products are stable. The formaldehyde concentration 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 hydrolyze 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 degradant. 

• 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 inorganic 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 sulfuric acid 

406 g THPS → 60 g formaldehyde 

• If the dose level of THPS is 10 ppm, as in our Industrial Fresh Water Systems 

application, it will produce only 1.5 ppm of formaldehyde 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 formaldehyde. 

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

• Formaldehyde is very soluble in water and the small amount present is not expected to be 

released into the air. 

1 

HOH2C P+ CH2OH SO4

2- 

 2 HOCH2 P CH2OH + 2HCHO + H2SO4

2-

2 

CH2OH

CH2OH O

CH2OH

O2
Attachment

EPA Case # 5034 Docket Number: EPA-HQ-OPP-2011-0067 

THPS (CAS: 55566-30-8) 

Rhodia 

12 May 2011 

• Formaldehyde release agents (FRAs) release formaldehyde 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 agent. 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 formaldehyde. 

• THPS is faster acting than formaldehyde. 

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

• Formaldehyde is deactivated by hydrogen sulfide, whereas THPS is not. 

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

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