        Review Report for D-Fructose (CASRN 57-48-7) Partial Exemption
                        
                                  October 2014
                                       
                      The Corn Refiners Association (CRA)
                                       
                   Docket Identifier:  EPA-HQ-OPPT-2014-0347

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 D-Fructose (hereafter referred to as fructose) (CASRN 57-48-7).  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: Based on the fact that fructose would be exempt from pesticide registration under 40 CFR 152.25(d) for foods used as pesticides certain conditions and the listing of fructose as exempt from the requirement of a tolerance under 40 CFR 180.950(a)(1)(i) as a minimal risk inert or active ingredient in pesticide formulations, which is supported by the Annex IV exemption from the European Union's (EU) Registration, Evaluation, and Authorization of Chemicals (REACH) registration and FDA regulations for its food uses, EPA determined that fructose has a low hazard to human health and the environment; 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's determination that fructose is exempt from pesticide registration and of minimal risk for use in other  pesticides and the regulation of fructose in food by FDA provide evidence of risk screening determinations in the United States for fructose; 5) Consideration E: Comparable processing and use information is not available from the European Union Chemical Agency (ECHA), because fructose is exempt from registration because of its minimal risk status; however, when considered in combination with the other substance-specific factors that weigh in favor of granting a partial reporting exemption, EPA does not regard the lack of comparable processing and use information as sufficient to affect the decision; and 6) Consideration F: Other than the pesticide and FDA regulations, EPA is unaware of any specific actions that have already taken by other agencies or authorities to manage risks relating to this substance.  

A direct final rule to add fructose 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 fructose 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 fructose 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 Organisation for Economic Co-operation and Development's (OECD)'s High Production Volume (HPV) Screening Information Data Set (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 fructose 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 fructose was reported for the 2006 IUR and the 2012 CDR.  EPA reviewed the 2012 CDR data for fructose and found that 8 sites reported domestically manufacturing and/or importing fructose with a nationally aggregated production volume of 10 million to 50 million 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 pound 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 erroneously gave the CASRN for corn steep liquor (CASRN 66071-94-1) at the beginning of the data section of the attachment to the fructose petition. EPA noted that the two substances are not analogs and did not use data for corn steep liquor in its fructose hazard assessment.  The petitioner attached the Decernis FDA Food Additives Summary Report and EPI Suite Modeling Summary Results for fructose to support this consideration.  In support of consideration C, the petitioner noted that FDA considers fructose safe for use in commonly consumed foods. 

Fructose would be eligible for the exemption from pesticide registration under 40 CFR 152.25(d) for foods when used as pesticides under certain conditions and under 40 CFR 180.950(a)(1)(i) as having a minimal risk exemption from the requirement for a tolerance for its residues resulting from its use as either an inert or an active ingredient in a pesticide chemical formulation, including antimicrobial pesticide chemicals, if such use is in accordance with good agricultural or manufacturing practices. In 1998, EPA established an exemption from tolerance requirements for all edible food commodities based on their long history of safe use in commerce and adequate regulation by FDA (63 FR66999, December 4, 1998).

EPA believes the exemption of fructose as a food from pesticide registration under 40 CFR 152.25(d) and from tolerance requirements at 40 CFR 180.950(a)(1)(i) based on the long history of safe use in food in commerce are supported by the similar EU Annex IV REACH registration exemption listing and provide sufficient evidence to address human health and environmental toxicity concerns for fructose.  Taken together, the weight of evidence indicates that this information is sufficient to partially exempt fructose 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 fructose in food. The petitioner also noted that fructose has not been the subject of information collection requirement by EPA under 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 2005, EPA denied an earlier petition for partial exemption for fructose, indicating that because fructose was part of EPA's HPV Challenge Program, EPA needed IUR processing and use information to put the hazard data received under the HPV Program in context in a risk screening assessment.  However, in light of the fact that other programs have determined that additional information is not needed because sufficient information is known to determine that fructose causes minimal risk, EPA does not believe that additional assessment of fructose is necessary.  See further discussion below under Consideration D.

EPA is not aware of any currently existing unmet information needs respecting the processing and use of fructose.  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 substance under the EU REACH registration, status under the voluntary EPA HPV Challenge Program, and status as a pesticide inert ingredient.  The petitioner indicated that fructose is listed in Annex IV, meaning it is exempt under the REACH registration program; however, the petitioner did not provide the rationale for the exemption, which is germane to this consideration. Fructose is exempt from REACH registration because sufficient information is known that it is considered to cause minimum risk because of intrinsic properties.  The additional information that the petitioner provided that fructose could be sponsored under EPA's HPV program does not mean that risk screening data is available and thus provides no support for this consideration.  It indicates that fructose is within the scope of the HPV program; however, because it has not been sponsored, there is no data available for an assessment.  The listing of fructose as a 4B pesticide inert is outdated.  Fructose would fall under 40 CFR 152.25(d) as a food exempt from pesticide registration and is listed under 40 CFR 180.950(a)(1)(i) as a commonly consumed food commodity which has a tolerance exemption as a minimal risk active or inert ingredient in pesticides.  This is based on a determination that any safety concerns regarding exposure to residues of edible food commodities have been addressed by the long history of safe use of these foods in commerce, as well as the adequate regulation of foods by the FDA (63 FR 37308, July 10, 1998).

EPA determined that although the petition only provided limited evidence of a risk screening determination by the EU for fructose in its discussion under Consideration D, EPA's determination that fructose is exempt from pesticide registration under certain conditions and is of minimal risk for use in other pesticides and the regulation of fructose in food by FDA provide evidence of risk screening determinations in the United States for fructose. Overall, EPA concluded that the availability of information relevant to Consideration D weighs in favor of partially exempting fructose from CDR reporting.

Consideration E:  The availability of comparable processing and use information.
The petitioner stated that the processing and use of fructose is well characterized and 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". While it is true that fructose's predominant use in food is well characterized, this is not a use subject to the Toxic Substances Control Act (TSCA).   Under Consideration B, the petitioner briefly noted that a small amount of fructose is used as a chemical intermediate and a filler in paper mills, both of which would be uses subject to TSCA.

Data from the non-confidential 2012 CDR database identified the following industrial uses: use as an intermediate in basic organic chemical manufacturing, and use as a fuel or fuel additive in petrochemical manufacturing.  The following consumer and commercial use was also identified:  use in fuels and related products.   

Fructose is exempt from EU REACH registration because of its minimal risk status; therefore, the ECHA database is not a source of processing and use information on fructose.  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 comparable processing and use 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 fructose 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 fructose. However, the petitioner did not specifically identify which uses of fructose are regulated by the foregoing governmental bodies or regulations, except for FDA.  However, the petitioner provided a list of citations for every instance where "fructose" is mentioned; and did not identify which of those citations were to actual regulations governing use of fructose.  Most of the citations allowed the use of fructose as an optional nutritive carbohydrate sweetener in various milk products as well as grapefruit juice and canned peas.

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, fructose is exempt from pesticide registration and 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.




