1

Review Report for Tripotassium Citrate (CASRN 866

- 84

- 2 ) Partial Exemption

October 2014

The Corn Refiners Association

Docket Identifier: EPA

- HQ

- OPPT

- 2014

- 0347

Note: Supporting petition information for c itric a cid (CASRN 77

- 92

- 9 ) and t risodium c itrate (CASRN 68

- 04

- 2) are addresse d in separate review report s

.

Summary of Decision : The U.S. Environmental Protection Agency (hereinafter “EPA” or the “Agency”) has determined that there is a low current interest in the processing and use information collected under the Chemical Data Reporting (CDR) rule (see 40 CFR Part 711) for 1,2,3

- P ropanetricarboxylic acid, 2

- hydroxy

- , potassium salt (1:3) (hereafter referred to as

t ripotassium c itrate

, CASRN 866

- 84

- 2) . This determination is based on the totality of information on the chemical substance, including an evaluation of the consideratio ns listed in 40 CFR 7l1.6(b)(2)(ii): 1) Consideration A: Current CDR information suggests that at least one site would have a production volume sufficient to trigger the need to report proc essing and use

information for the 2016 CDR (25,000 pound threshold ); 2) Consideration B: The prior evaluation of tripotassium citrate by EPA’s High Production Volume (HPV) Challenge Program in conjunction with the Organisation of Economic an d Co

- operation Development’s (O E C D)

Swiss

- sponsored Screening Information Data Se t (SIDS) Initial Assessment Report (SIAR)

, the U.S. Food and Drug Administration (FDA) treatment of tripotassium citrate as a prior sanctioned substance for use as a stabilizer when migrating from food packaging material (21 CFR 181.29), the similarity of tripotassium citrate to citric acid which FDA considers Generally Recognized As Safe (GRAS, 21 CFR 182 and 184) for use as a direct human food ingredient

, and the Database of Select Committee on GRAS Substances (SCOGS) report for tripotassium citrate when used in reasonable amounts in accordance with prescribed tolerances and limitations,

indicates a low concern for human health. Based on the available ecotoxic ity data for citric acid and trisodium citrate from the HPV Challenge Program hazard assessment, the Swiss OECD SIAR, EPA’s Office of Pesticide Program’s (OPP) Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) minimal risk tolerance exemption unde r 40 CFR 180.950(e), and

OPP ’s final R egistration R eview D ecision for citric acid , tripotassium citrate appears to be of low toxicity to aquatic organisms. Concerning environmental fate, EPA determined that tripotassium citrate has the potential to biodegr ade, will not persist in the environment, and has a low potential for bioconcentration or bioaccumulation ; 3) Consideration C: EPA is not aware of any currently existing unmet information needs for CDR processing and use information for this

chemical subst ance; 4) Consideration D: The availability of complementary risk screening information was not sufficiently characterized in the petition; however, EPA recognized that the

data reviewed for the OE CD SIAR, EPA’s HPV Challenge Program’s Risk Based Prioritiza tion ( RBP ) and supporting Hazard Characterization (HC)

, OPP’s final Registration Review Decision

, and OPP’s 40 CFR 180.950(e) minimal risk tolerance exemption provide evidence of complementary risk screening information for tripotassium citrate ; 5) Consideration E: Comparable processing and use information is available in the European Chemical Agency’s (ECHA’s) database, and although it is for use of products in Europe and not the United States, it provides an indication o f uses that may occur in the United States ; and 6) Consideration F: EPA2

is unaware of any specific actions that have already been taken by other agencies or authorities to manage risks relating to this substance.

A direct final rule to add t ripotassium c itrate , using its TSCA In ventory name, 1,2,3

- P ropanetricarboxylic acid, 2

- hydroxy

- , potassium salt (1:3) to the list of chemical substances partially exempt from reporting CDR processing and use information in 40 CFR 711.6(2)(b)(iv) will be published in the Federal Register. The f inal listing is pending, based on possible adverse responses to the F ederal R egister notice. I f the level of interest in the CDR processing and use information for this chemical substance were to change after final listing, EPA may reevaluate the listing a nd pursue amendment of the listing as appropriate.

Persons submitting information in accordance with the CDR rule can still report processing and use information even if a chemical substance is partially exempt, so that their chemical substances may be considered for safer substitute analyses.

Background : EPA received a petition from t he Corn Refiners Association (CRA) 1 (hereinafter the “petitioner”) , requesting that tripotassium citrate be added to the 40 CFR 711.6(b)(2)(iv) list of specific chemical substances that are exempt from the reporting requirements of 40 CFR 711.15(b)(4) ( i.e. , exempt from requirements to report industrial processing and use and

commercial/consumer use informat ion). The chemical substances already included on this “partial exemption” list are substances for which EPA has previously determined that there is a low current interest in the CDR processing and use information. However, as stated in the preamble to t he Inventory Update Reporting Amendments (IURA) rule promulgated on January 7, 2003, “...the need for processing and use information under IURA changes over time. The inclusion of a chemical substance under this partial exemption is not based on the potenti al risks of a chemical. This partial exemption is solely intended to provide a tool to assist the Agency in better managing the collection of processing and use information...” and is also “...based on the Agency’s current assessment of the need for collectin g IURA processing and use information.” 2 Additionally, the preamble states, “[i]n determining whether there is low current interest in IUR processing and use information related to a specific chemical substance, EPA will look to the specific circumstance s surrounding the chemical in question, and may use one or more of the considerations identified below, and/or considerations not identified below, to make an informed decision.” The considerations used by EPA in reviewing this petition and an analysis of how

those considerations relate to t ripotassium c itrate are set forth below.

Discussion: EPA considered information submitted with the petition, as well as other information including, but not limited to: whether the petitioned chemical substance is lis ted on the Emergency Planning and Community Right to Know Act (EPCRA) , Section 313 list of Toxic Chemicals and thus is reportable to the Toxics Release Inventory (TRI); 2012 CDR submissions for the chemical substance; evaluations available through the EPA’ s Integrated Risk Information System (IRIS), the International Agency for Research on Cancer (IARC) , the OECD’s HPV

1 CDR Partial Exemption Petition (April 21, 2014) (Hereinafter “The Petition”); From: Herb Estreicher, Keller and Heckman LLP; To: OPPT CDR Submission Coordinator, U.S. Environmental Protection Agency; Re: “Request for exemption of citric acid, trisodium citrate and tripotassium citrate from TSCA chemical data reporting (CDR) processing and use information reporting requirements in 2016” (2 pp.), with attachment titled “CDR petition for certain food

- use substances 40 C.F.R. § 711.415(b)(2)(ii)(A) criterion information”(14 pp.).

2 Federal Register Volume 68, Issue 4 (January 7, 2003) p. 848

- 906. http://www.gpo.gov/fdsys/pkg/FR

- 2003

- 01

- 07/pdf/02

- 32909.pdf

Accessed: 8/08/2013.3

SIDS program, or the EPA’s HPV Challenge Program; whether the substance is subject to other regulatory programs administered by EPA or other federal agencies ; and other information researched by EPA to supplement the petition.

The petitioner provided information concerning t ripotassium c itrate from a variety of sources and linked it to specific considerations cited in 40 CFR 711.6(b)(2)(ii).

Consideration A: Whether the chemical qualifies or has qualified in past IUR collections for the reporting of the information described in 40 CFR 711.15(b)(4).

The petitioner indicated that t ripotassium c itrate ( CASRN 866

- 84

- 2 ) was reported for the 2006

IUR and the 2012 CDR. EPA reviewed the 2012 CDR data for t ripotassium c itrate and found

that 5 sites reported domestically manufacturing and/or importing t ripotassium c itrate with a nationally aggregated production volume of 1,903,962 pounds in 2011.

EPA has concluded that at least one manufacturing site would likely have a production volume sufficient to trigger the need to report processing and use informati on for the 2016 CDR (25,000 pound threshold). Thus, EPA concludes that the other consideration s are ripe for evaluation.

Consideration B: The chemical substance’s chemical and physical properties or potential for persistence, bioaccumulation, health effects, or environmental effects (considered independently or together).

The petitioner submitted summary information from EPA’s HPV Challenge Program for carboxylic acids and salts c ategory that was submitted by the American Chemistry Council’s Acetic Acid and Salts Panel on April 16, 2003. EPA published an Initial RBP document 3 and

support ing HC 4 in August 2008. The petitioner noted that FDA affirms the use of tripotassium citrate as Generally Recognized As Safe (GRAS, 21 CFR 184.1 62 5) for use as direct human food ingredients. The safety of these ingredients have been evaluated under the comprehensive safety review conducted by the agency (as specified in 21 CFR parts 182 and 184).

EPA assessed tripotassium citrate along with citric acid and tri sodium citrate as a subcategory of the carboxylic food acids and salts category based on str uctural, functional and toxicological properties and published a Risk

- Based Prioritization (RBP) document in August 2008

. 3
Additionally, tri potassium citrate is also listed under 40 CFR 180.950(e) as having a tolerance exemption as a minimal risk active o r inert ingredient in pesticides. In a 2002 Decision Memo, reassessing the tolerance exemption, EPA’s hazard characterization concluded that there is no

available informati o n indicative of a hazard, significant adverse effects to the general public or any population for tri potassium citrate

. 4 EPA reviewed hazard information during the development of the RBP and pesticide determinations. EPA’s conclusions are summarized in the

sections below.

3 Initial RBP of Carboxylic Food Acids and Salts Category. http://www.epa.gov/chemrtk/hpvis/rbp/CAT_Carboxylic%20Food%20Acids_Web_RBP_August%202008.pdf

. Accessed 8 July 2014

4 Supporting Documents for Initial RBP of Carboxylic Food Acids and Salts Category. http://www.epa.gov/chemrtk/hpvis/rbp/CAT_Carboxylic%20Food%20Acids_Web_SuppDocs_August%202008.pdf4

EPA also considered other sources of information to inform its decisions on human health and environmental toxicity, and environmental fate, including the 2001 Swiss

- sponsored OECD SIAR for citric acid, 5 and FDA’s affirmation of tri potassi um citrate as Generally Recognized As Safe (GRAS, 21 CFR 184.1 625) for use as direct human food ingredients.

Human Health Effects

. EPA’s Hazard Characterization (HC) supporting the RBP concluded that

t he acute oral toxicity for the supporting chemical ci tric acid is low. The supporting chemical

c itric acid is irritating to rabbit skin and severely irritating to the rabbit eye. At h igh doses

, the supporting chemical trisodium citrate showed no adverse effects in oral reproductive and developmental toxicity studies (species and sex not identified)

. The supporting chemical c itric acid did not show potential to induce genetic mutations; no data are available for chromosomal

aberrations.

Environmental Effects

. Tripotassium citrate has a low potential h azard to aquatic organisms. Based on the available ecotoxicity data for citric acid and trisodium citrate from the HPV Challenge Program HC , the Swiss OECD SIAR

, and the OPP decision memo
, tripotassium

citrate appears to be of low toxicity to aquatic orga nisms.

Environmental Fate

. Tr ipotassium citrate is expected to have high mobility in soil, and is expected to partition primarily to water and soil if released to the environment. B ased on experimental data for citric acid and trisodium citrate from seve ral biodegradation tests, tripotassium citrate is expected to be readily biodegradable. EPA ran the Estimation Programs Interface Suite (v. 3.20) modeling software to support the HPV Program Risk

- based prioritization screening assessment and determined tha t tripotassium citrate has a low potential to

bioaccumulate.

EPA believes tha t the Agency’s HPV Challenge Program’s RBP and supporting HC

, OPP FIFRA tolerance exemptions, and the OPP decision memo are supported by the OECD SIAR

and provide sufficient evidence to address human health and environmental toxicity concerns for tripotassium citrate. Taken together, this information is sufficient to weigh in favor of partially

exempt ing tripotassium citrate from CDR reporting based on huma n health and environmental

concerns covered under C onsideration B.

Consideration C: The information needs of EPA, other federal agencies, tribes, states, and local governments, as well as members of the public.

The petitioner stated that it was unaware of any unmet information needs of EPA, other federal agencies, tribes, states, local governments, or members of the public in light of FDA regulatory

clearances available for t ripotassium c itrate in food applications and the extensive data published

on th e ECHA website. The petitioner also noted that t ripotassium c itrate has not been the subject of information collection requirement by EPA under the Toxic Substances Control Act ( TSCA ) (other than CDR), the Interagency Testing Committee (ITC), or the Agenc y for Toxic Substances and Disease Registry (ATSDR). The petitioner asserts that there is sufficient information available, and there have been no previous information requests.

5 Swiss sponsored 2001 SIDS Initial Assessment Report published by UNEP. http://www.in chem.org/documents/sids/sids/77929.pdf Accessed 08 July 20145

In 200 6 , EPA denied an earlier petition for partial exemption for tripotassium citrate , indicating

that there was no basis to believe that the 300,000 pound threshold volume for reporting processing and use information would be met for t ripotassium citrate

. 6 Since then, the nationally aggregated production volume for tripotassium citrate has increased and the threshold volume for reporting processing a nd use in 2016 will be 25,000 pounds . As noted under Consideration A, EPA has concluded that at least one m anufacturing site would likely have a production volume sufficient to trigger the need to report proc essing and use information for the 2016 CDR. Additionally, i n 2009, EPA complet ed a RBP document for tripotassium citrate as part of the carboxylic food a cids and salts c ategory, 7 using processing and use information from

the 2006 IUR.

EPA is not aware of any currently existing unmet information needs respecting the processing

and use of t ripotassium c itrate and agrees that recent processing and us e inf ormation for this

chemical is otherwise available to government agencies and the public on the ECHA website. Although the uses in Europe may not be exactly the same as the uses in the United States, EPA believes they can provide an indication of potential uses on which to base further analysis,

should the chemical substance be of interest. Overall, EPA regards Consideration C as weighing in favor of establishing a partial exemption for this chemical substance.

Consideration D: The availability of other co mplementary risk screening information.

The petitioner included a table which provided the status of the petitioned substance on the European Commission Annex II list of low risk substances, exemption determinations by the European Union for the REACH program, status under the voluntary E PA HPV Challenge Program and safety determinations for low toxicity pesticide inerts. However , no discussion was provided linking the status to the availability of risk screening information. Therefore, it is

unclear why the petitioner believes this table relates to Consideration D, the availability of other complementary risk screening information. EPA notes that the fact that the petitioned substance

w as not present on most of these lists provided no evidence of the availability of risk screening information nor were explanations given of the significance of the chemicals not being listed on the two European lists. The significance of the chemical not being listed on the two European lists was not explained. T he fac t that tripotassium citrate could be sponsored under the HPV program does not mean that risk screening data is necessarily available and that entry is outdated

anyway

. T he petitioner did not note the availability of an OECD SIAR for citric acid (which is a suitable analog for tripotassium citrate) and an EPA RBP document ( which included tripotassium citrate, which had been sponsored in the HPV program ) , both of which conclude that citric acid

and its salts present a low concern . The identification of trip otassium citrate as a 4A pesticide

inert does not provide information about risk screening

. It is more useful to note that Tripotassium citrate is listed under 40 CFR 180.950(e) as having a tolerance exemption as a minimal risk active or inert ingredient in pesticides. Additionally, upon review of all available information, EPA issued a Decision Memo in March 200 8 reassessing the tolerance exemption

and concluding that there are not likely to be any unreasonable adverse effects to the U.S.

6 Letter from Charles M. Auer, EPA, to Herbert Estreicher, Esq. and Martha E. Marrapese, Esq., “Petition for Partial Exemption from Inventory Update Reporting Requirements, Docket No. EPA

- HQ

- OPPT

- 2004

- 0071”, January 31, 2006.

7 Initial RBP of Carboxylic Food Acids and Salts Category. http://www.epa.gov/chemrtk/hpvis/rbp/CAT_Carboxylic%20F ood%20Acids_Web_RBP_August%202008.pdf Accessed 7 July 20146

population in g eneral, and to infants and children in particular, or to non

- target organisms or the

environment from the use of the tolerance exemption.

EPA determined that the petition er did not provide evidence that complementary risk screening

information is available for t ripotassium c itrate in its discussion under Consideration D

. However, the data reviewed for the OECD SIAR, EPA’s RBP and supporting HC

, EPA ’s FIFRA 40 CFR 180.950(e) minimal risk tolerance exemption and the decision memo affirming it provide evidence of complementary risk screening information for tripotassium citrate

. Overall, EPA concluded that the availability of information relevant to Consideration D weighs in fa vor of partially exempting tripotassium citrate from CDR reporting.

Consideration E: The availability of comparable processing and use information.

While the petitioner indicated that t ripotassium c itrate is predominantly used in food (which is not a use subject to TSCA), the information they provided from the ECHA database indicated a broader range of uses. The petitioner asserted that TSCA

- regulated exposures are comparable to, or less significant than, the food

- use exposures associated with these substances, which have already been shown to be “safe.” The petitioner included a list of uses obtained from ECHA’s

database.

The uses in the ECHA database are for the European Union and indicate that t ripot assium c itrate may have broader use in Europe than in the United States. Data from the non

- confidential 2012

CDR database identifi ed the following industrial use : flame retardants. The follow ing consumer

and commercial use was also identified: non

- TSCA u se.

EPA agrees that other recent processing and use information, available from ECHA is sufficiently comparable to CDR processing and use information to weigh in favor of granting a partial reporting exemption for this chemical substance. While the ECHA information may not be completely representative of use in the United States, EPA concluded in this case (in view of all relevant considerations) that the ECHA information is a reasonable surrogate indicator of possible United States processing and use. EPA also recognizes that the ECHA database does not specify the amounts of t ripotassium c itrate to each use. But when considered in combination

with the other substance

- specific factors that weigh in favor of granting a partial reporting exemption (e.g., the evidence that the potential human health effects and/or environmental effects would be low) EPA does not regard the lack of use

- by

- use volume information as

sufficient to affect the decision.

Consideration F: Whether the potential risks of the chemica l substance are adequately managed by EPA or another agency or authority.

The petitioner generally indicated that the manufacturing and use of t ripotassium c itrate primarily falls within the jurisdiction and authority of the FDA. The petitioner also stated that EPA, the Occupational Safety and Health Administration (OSHA), the National Institute for Occupational Safety and Health (NIOSH), and the Consumer Product S afety Commission (CPSC) regulate the manufacture and use of t ripotassium c itrate . However, the petitioner did not specifically identify which uses of t ripotassium c itrate are regulated by the foregoing7

governmental bodies or regulations, except for the FDA regulation at 21 CFR 175.105, which covers uses of substances as components of adhesives used in food packaging

. This citation is not useful as it does not specifically mention the substance. More to the point is the fact that tripotassium citrate is lis ted as a prior sanctioned substance for use as a stabilizer under 21 CFR

181.29.

Overall, although the petition included the general claim that this substance is already “controlled adequately under other regulatory regimes,” it did not identify how any particular agency or authority was managing any particular risk relating to this substance, let alone how such risk management actions should bear on EPA’s level of current interest in processing and

use information.

As noted above, tripotassium citrate i s approved for use as a minimal risk active or inert ingredient in pesticides. EPA is unaware of any specific actions that have already taken by other agencies or authorities to manage risks relating to this substance. However, given the evidence

that th e potential human health effects and/or environmental effects would be low, EPA does not therefore assume that this substance would likely be the subject of risk management actions in

the future. Thus

, in this case, EPA believes this consideration weighs neither in favor of nor against adding the substance to the CDR partial exemption list.