     Review Report for Trisodium Citrate (CASRN 68-04-2) Partial Exemption
                        
                                 October 2014

                      The Corn Refiners Association (CRA)
                   Docket Identifier:  EPA-HQ-OPPT-2014-0347
Note: Supporting petition information for citric acid (CASRN 77-92-9) and tripotassium citrate (CASRN 866-84-2) are addressed in separate supporting review reports. 

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-Propanetricarboxylic acid, 2-hydroxy-, sodium salt (1:3) (hereafter referred to as trisodium citrate, CASRN 68-04-2).  This determination is based on the totality of information on the chemical substance, including an evaluation of the considerations 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 processing and use information for the 2016 CDR (25,000 pound threshold); 2) Consideration B: The prior evaluation of trisodium citrate by EPA's High Production Volume (HPV) Challenge Program in conjunction with the Organisation of Economic and Co-operation Development's (OECD) Swiss-sponsored Screening Information Data Set (SIDS) Initial Assessment Report (SIAR) and the U.S. Food and Drug Administration's (FDA) affirmation of trisodium citrate as Generally Recognized As Safe (GRAS, 21 CFR 182.1 and 184) for use as a direct human food ingredient indicates a low concern for human health.  Based on the available ecotoxicity information from the HPV Challenge Program hazard assessment, the Swiss OECD SIAR, the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) minimal risk tolerance exemption (40 CFR 180.950(e)),  and the U.S. EPA's Office of Pesticide Program's (OPP's) final Registration Review Decision, trisodium citrate appears to be of low toxicity to aquatic organisms.  Concerning environmental fate, EPA determined that trisodium citrate has the potential to biodegrade, 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 substance; 4) Consideration D: The availability of complementary risk screening information was not sufficiently characterized in the petition; however, EPA recognizes that the data reviewed for the OECD SIAR, EPA's HPV Challenge Program Risk Based Prioritization (RBP) and supporting Hazard Characterization (HC), OPP's final Registration Review Decision, and the EPA FIFRA 40 CFR 180.950(e) minimal risk tolerance exemption provide evidence of complementary risk screening information for trisodium 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 of uses that may occur in the United States; and 6) Consideration F: EPA 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 trisodium citrate, using its Toxic Substances Control Act (TSCA) Inventory name, 1,2,3-Propanetricarboxylic acid, 2-hydroxy-, sodium 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 final listing is pending, based on possible adverse responses to the Federal Register notice. If 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 and 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 the Corn Refiners Association (CRA) (hereinafter the "petitioner"), requesting that trisodium 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 information).  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 the 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 potential 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 collecting IURA processing and use information."   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 circumstances 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 trisodium citrate 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 listed 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 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 trisodium citrate 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 trisodium citrate was reported for the 2006 IUR and 2012 CDR.  EPA reviewed the 2012 CDR data for trisodium citrate and found that 11 sites reported domestically manufacturing and/or importing trisodium citrate with a nationally aggregated production volume of 14,333,759 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 information for the 2016 CDR (25,000 lb threshold). Thus, EPA concludes that the other considerations 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 category that was submitted by the American Chemistry Council's Acetic Acid and Salts Panel on April 16, 2003. EPA published an Initial RBP document with a supporting HC in August 2008.  The petitioner noted that FDA affirms the use of trisodium citrate (CASRN 68-04-2) as Generally Recognized As Safe (GRAS, 21 CFR 184.1751) for use as direct human food ingredients.  The safety of these ingredients have been evaluated under the comprehensive safety review conducted by FDA (as specified in 21 CFR parts 182 and 184). 

EPA assessed trisodium citrate along with citric acid and tripotassium citrate as a subcategory of the carboxylic food acids and salts category based on structural, functional and toxicological properties and published a Risk-Based Prioritization (RBP) document in August 2008[cite].  Additionally, trisodium citrate is also listed under 40 CFR 180.950(e) as having a tolerance exemption as a minimal risk active or inert ingredient in pesticides.  In a 2002 Decision Memo, reassessing the tolerance exemption, EPA's hazard characterization concluded that there is no available information indicative of a hazard, significant adverse effects to the general public or any population for trisodium citrate (cite).  EPA reviewed hazard information during the development of the RBP and pesticide determinations.  EPA's conclusions are summarized in the sections below.

EPA also considered other sources of information to  confirm its decisions on human health, environmental toxicity, and environmental fate, including the 2001 Swiss-sponsored OECD SIAR for citric acid  and FDA's affirmation that trisodium citrate (CASRN 68-04-2) as Generally Recognized As Safe (GRAS, 21 CFR 184.1751) for use as direct human food ingredients.  

Human Health Effects. EPA's Hazard Characterization (HC) supporting the RBP concluded that the acute oral toxicity for the supporting chemical citric acid is low.  The supporting chemical citric acid is irritating to rabbit skin and severely irritating to the rabbit eye.  At high doses, trisodium citrate showed no adverse effects in oral reproductive and developmental toxicity studies (species and sex not identified).  The supporting chemical citric acid did not show potential to induce genetic mutations; no data are available for chromosomal aberrations.

Environmental Effects. Trisodium citrate has a low potential hazard to aquatic organisms.  Based on the available ecotoxicity data for trisodium citrate and citric acid from the HPV Challenge Program HC, the Swiss OECD SIAR, and the OPP decision memo, trisodium citrate appears to be of low toxicity to aquatic organisms.

Environmental Fate. Trisodium citrate is expected to have high mobility in soil, and is expected to partition primarily to water and soil if released to the environment. Based on experimental data for trisodium citrate and citric acid, trisodium 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 that trisodium citrate has a low potential to bioaccumulate.
EPA believes that the EPA's HPV Challenge Program's HC, 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 trisodium citrate. Taken together, this information is sufficient to weigh in favor of partially exempting trisodium citrate from CDR reporting based on human health and environmental concerns covered under consideration 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 trisodium citrate in food applications and the extensive data published on the ECHA website.  The petitioner also noted that trisodium citrate 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 Agency for Toxic Substances and Disease Registry (ATSDR). The petitioner asserts that there is sufficient information available, and there have been no previous information requests.

In 2006, EPA denied an earlier petition for partial exemption for trisodium citrate, indicating that because trisodium citrate was part of EPA's HPV Challenge Program, the Agency needed IUR processing and use information to put the hazard data received under the HPV Program in context in a risk screening assessment.  In 2009, EPA completed a RBP document for trisodium citrate as part of the carboxylic food acids and salts category, 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 trisodium citrate and agrees that recent processing and use information for this chemicals is otherwise available to government agencies and the public on the ECHA website. Although the uses in Europe noted in ECHA information 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 (for a detailed summary of specific uses see Consideration E). Overall, EPA regards Consideration C as weighing in favor of establishing a partial exemption for this chemical substance.

Consideration D:  The availability of other complementary risk screening information.

The petitioner included a table which provided the status of the petitioned substances 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 EPA 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 how this table relates to Consideration D, the availability of other complementary risk screening information.  EPA notes that the fact that the petitioned substances were 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.  Also, the fact that trisodium citrate could be sponsored under the HPV program does not mean that risk screening data is necessarily available and that entry is outdated.
In this case, the petitioner should have noted the availability of an OECD SIAR for citric acid (which is a suitable analog for trisodium citrate) and an EPA RBP document (which included trisodium 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 trisodium citrate as a 4A pesticide inert does not provide information about risk screening.  It is more useful to note that Trisodium 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 2008 reassessing the tolerance exemption and concluding that there are not likely to be any unreasonable adverse effects to the U.S. population in general, 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 although the petitioner did not provide evidence that complementary risk screening information is available for trisodium citrate under Consideration D, 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 trisodium citrate. Overall, EPA concluded that the availability of information relevant to Consideration D weighs in favor of partially exempting trisodium citrate from CDR reporting.

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

While the petitioner indicated that trisodium citrate 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 trisodium citrate may have broader use in Europe than in the United States.  Data from the non-confidential 2012 CDR database identified the following industrial uses: fillers, processing aids, and surface active agents.  The following consumer and commercial uses were also identified: ink, toner and colorant products, laundry and dishwashing products and personal care products.

EPA agrees that other recent processing and use information, available from ECHA is sufficiently comparable to CDR processing and use information to favor 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 trisodium citrate 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 chemical substance are adequately managed by EPA or another agency or authority.

The petitioner generally indicated that the manufacturing and use of trisodium citrate 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 Safety Commission (CPSC) regulate the manufacture and use of trisodium citrate. However, the petitioner did not specifically identify which uses of trisodium citrate are regulated by the foregoing governmental bodies or regulations, except for the FDA regulations covering the use of trisodium citrate as a food additive in a variety of products and as part of resinous and polymeric coatings and packaging materials.  

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, trisodium citrate is 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 the 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.


