United States Chemical Safety December 2012 Environmental Protection and Pollution Prevention Agency (7510P)



# Nabam Registration Review: Final Work Plan December 2012Docket Number: EPA-HQ-OPP-2012-0339 www.regulations.gov

3 of 11 Nabam Registration Review Team

Human Health & Environmental Effects Nathan Mottl William Hazel Jonathan Chen Steven Malish Srinivas Gowda James Breithaupt William Erickson

Risk Management Wanda Henson Lance Wormell

Office of General Counsel Philip Ross

________________________________________ Supporting documents for the Nabam Case may be found in the registration review docket EPAHQ-OPP-2012-0339 located on the internet at www.regulations.gov.Docket Number: EPA-HQ-OPP-2012-0339 www.regulations.gov

4 of 11 Introduction

This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the Agency”) for the registration review of Na bam (Case 0641). The work plan includes the expected registration review timeline. The work plan also addresses public comments received concerning the Preliminary Work Plan (PWP) in the Summary Document which was posted in the Nabam registration review docket, and any other comments concerning the initial docket postings. The Summary Document provided information on what EP A knows about the pesticide and what additional risk analyses and data or information the Agency believes are needed to make a registration review decision.

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. Changes in science, public policy an d pesticide use practices will occur over time. The registration review program is intended to ma ke sure that, as the ability to assess risk evolves and as policies and practi ces change, all registered pestic ides continue to meet that statutory standard. The public pha se of registration review begins when the initial docket is opened for each case. Information on this program is provided at: http://www.epa.gov/oppsrrd1/ registration_review/.

The Nabam Preliminary Work Plan (PWP) (P C Code 014503) was published on July 6, 2012 and the 60-day comment period ended on September 10, 2012. The Preliminary Work Plan document is available on www.regulations.gov docket number EPA-HQ-OPP-2012-0339.

The first product containing Disodium ethylene bisdithiocarbamate (Nabam or EBDC) (PC Code 014503) as an active ingredient wa s registered in the United Stat es in 1948. Currently, there are eight products containing EBDC as an active ingredient registered with EPA. Algicide, bactericide, fungicide, slimicide, and microbici de/microbistat in indus trial process and water systems such as air washer water, cooling towe r water, drilling fluids , evaporative condenser water, heat exchanger systems, flood water, flue gas desulferization thic keners, fracturing fluids, industrial recirculating water coo ling tower, oil recovery drilling mud, oil recovery packer fluid, oilfield drilling muds, workover or completion fluids, oilfield water treatment and water floods, petroleum industries, secondary and tertiary petr oleum recovery, secondary oil recovery injection water, pulp and paper mill fresh water, pulp a nd paper mill systems, sugar beet processing equipment, sugar beet processing water, sugarcane processing water, sugar industries, sugar beet juice, sugarcane juice, sugarcane mill systems, sugarcane processing equipment, beet sugar mills, and cane sugar mills. Nabam is also used as a preservative in hydrocarbon fuels, lubricants and hydraulic fluids. Nabam is a member of the Ethylene bisdithiocarbamate (EBDC) group of chemicals which are metabolized to ETU (e thylene thio urea) in the body and in the environment.

There are no EPA established tolerances or exem ptions from the requirem ent of tolerances for nabam. FDA has deemed the indirect food additive use of nabam safe when used as a slimicide in paper/paperboard producti on with no maximum treatment c oncentration specified (21 CFR 176.300). FDA has also deemed the secondary direct food additive use of nabam safe when usedDocket Number: EPA-HQ-OPP-2012-0339 www.regulations.gov

5 of 11 as an antimicrobial in sugar production at 3 ppm expressed in terms of the raw sugar beets or sugarcane [21 CFR 173.320(b)(2) and –(3)].

The Agency completed a Reregistration Elig ibility Decision (RED) for Nabam in 1995.

Documents associated with the registrati on review of Nabam can be viewed at www.regulations.gov in docket EPA-HQ-OPP-2012- 0339. Below is a summary of the issues relevant to this registration review case.

Comments Received on the Preliminary Work Plan

The Agency received no comments during the pu blic comment period on the initial docket. In the PWP, the Agency solicited comments on speci fic topics: environmental justice, water body impairment, trade irritants, a nd structure activity relationships . No comments or information were received during the public comme nt period concerning these issues.

Note that on June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 - Ecological Effects Tests - including rem oval of the Tier designation on 850.5400 (Algal Toxicity). For more information see "Final Test Guidelines; OC SPP 850 Series; Notice of Availability" 77 FR 38282, June 27, 2012. Based on these changes, the Algal Toxicity study (GLN 850.5400) anticipated as being required in the PWP has been replaced by the following harmonized guidelines:

 850.4500: Algal Toxicity

 850.4550: Cyanobacteria ( Anabeana flos-aquae ) Toxicity

The work plan and timeline described in the PW P remain as they were presented initially. Further, this document makes final the work pl an for the Nabam registration review process.

Risk Assessments and Anticipated Data Needs

The Agency will conduct a comprehensive ecologi cal risk assessment, including an endangered species risk assessment, for all uses of Naba m. The Agency will conduct a human health risk assessment. The Agency expects to require additi onal data for use in conducting the registration review for Nabam.

Ecological Risk Asse ssment Status and Anticipated Data Needs

 The most recent quantitative ecological risk assessment for nabam was completed in support of the 1996 RED.

 The Agency has not conducted a risk asse ssment that supports a complete endangered species determination for Nabam. The ecological risk assessment plan ned during registration review will allow the Agency to determine whether Nabam’s use has 'no effect' or 'may affect' federally listed threaten ed or endangered species (liste d species) or their designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, th e Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisherie s Services (the Services), as appropriate.Docket Number: EPA-HQ-OPP-2012-0339 www.regulations.gov

6 of 11  Paper and paperboard mills and sugar beet/cane processing facilities are associated with a major waste water discharge that have the pot ential to contaminate drinking water for consumption by humans and livestock. As a re sult, nabam and/or ethylene thiourea (ETU) – the most stable, toxic and mobile degradate of nabam – could potentially pass through waste water treatment plants (WWTPs).

 The Agency anticipates the need to require th e following additional ecological data for use in conducting the registration review of Nabam.

850.4500: Algal Toxicity 1 850.4550: Cyanobacteria ( Anabeana flos-aquae ) Toxicity 1 850.1400 -- Fish early-life stage to xicity test (freshwater) 850.1450 -- Fish early-life stage to xicity test (saltwater)

 The Agency anticipates the need to require th e following additional environmental fate data for use in conducting the regi stration review of Nabam.

850.6800 -- Activated sludge, resp iration inhibition test 2 835.3110 -- Ready Biodegradability 2
835.3220 -- Porous Pot Test 2 835.3280 -- Simulation Tests to Assess the Biodeg radability of Chemicals Discharged to Wastewater 2 835.3240 -- Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units 2

For more information, please refer to Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Registration Review of Nabam , located in the docket.

Human Health Risk Assessment Status and Anticipated Data Needs

 The most recent human health risk assessmen t for nabam was performed to support the 1996 RED.

1 Results for studies conducted with nabam and ETU for (i) the freshwater green alga, Selenastrum capricornutum

, (ii) the freshwater diatom, Navicula pelliculosa , (iii) the marine diatom, Skeletonema costatum , and (iv) the cyanobacteria species Anabaena flos-aquae , must be submitted to satisfy this requirement. Final 850 guidelines for the algal testing were posted in June 2012. The Pub lic Draft OPPTS 850.5400 Algal Toxicity guideline was split into two separate guidelines and renumbered with the cy anobacteria species separated into OCSPP 850.4550 and the other three species under OCSPP 850.4500.
2 The results of the Activated Sludge Respiration Inhi bition Test (ASRI) will dete rmine which of these four biodegradation tests is/are required. If the ASRI test EC 50 is less than or equal to 20 mg/L, then either the (i)Biodegradation in Activated Sludge Study or (ii) Si mulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the Porous Pot Test is required. If the ASRI test EC50 is greater than 20 mg/L, then the registrant must conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sl udge Units or c) the Porous Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing is required. If, however, the antimicrobial fails the Ready Biodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot study is requiredDocket Number: EPA-HQ-OPP-2012-0339 www.regulations.gov

7 of 11 Dietary Assessment

 Registered nabam uses that could potentially re sult in residues in food are use as a slimicide in the pulp slurry of paper mills and in beet a nd cane sugar extraction water. Most labels state that treated paper and paperboard may be used for food packaging. FDA has deemed the indirect food additive use of nabam safe wh en used as a slimicide in paper/paperboard production with no maximum treatment concen tration specified (21 CFR 176.300). FDA has also deemed the secondary direct food addi tive use of nabam safe when used as an antimicrobial in sugar producti on at 3 ppm expressed in term s of the raw sugar beets or sugarcane [21 CFR 173.320(b)(2) and –(3)].

Tolerances and Intern ational Harmonization

 There are no pesticide tolerances or exempti ons from the requirement of tolerances for nabam under the jurisdiction of EPA. Naba m is, however, cleared by the Food and Drug Administration (FDA) as an indir ect food additive and formulated due to its use in sugar mill grinding, crusher, and/or diffuse r systems (21 CFR 173.320(b)(3) at levels less than or equal to 3.0 ppm on raw sugar cane or sugar beets.

Occupational and Residen tial Assessment and Risk

 The Agency conducted an occupational and residential exposure assessment for the RED in 1996 (D208114, D215335). The RED imposed mitigation requirements that stipulated that “all products must be loaded and transferred only using a metering-pump system or a closed loading/application system.” All the existi ng labels now have language that specifies metering pumps or closed loading systems and occupational handler and postapplication exposures are minimized. As a result, the Agen cy does not anticipate the need to develop occupational handler and/or postapplication assessment s for registration review.

 For nabam there is no potential exposure to resi dential handlers. Therefore, residential risk assessments are not required. Nabam registered products contain the label statement for "industrial use only" and are, therefore, intended for occupational use. None of the registered nabam uses are likely to involve direct applications at residential sites; th erefore, the Agency will not need to develop nabam residential handler and/or residential postapplication assessments for registration review

Aggregate and Cumulative Exposure and Risk

 In examining aggregate exposure, EPA take s into account the available and reliable information concerning exposures to pesticide residues in food and drinking water, and nonoccupational pesticide exposures. Dietary (food and drinking water) expo sures of concern are anticipated for nabam and ETU. Residential expo sures are not of concern. An aggregate risk assessment for nabam as well as ETU is needed to assess aggregate exposures from food and drinking water.Docket Number: EPA-HQ-OPP-2012-0339 www.regulations.gov

8 of 11  EPA does not have, at this time, available da ta to determine whether Nabam has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment.

 For the purposes of this Registration Review, EPA has assumed that Nabam does not have a common mechanism of toxicity with other subs tances when used as an antimicrobial as registered.

Human Health Anticipated Data Needs

 The Agency anticipates the need to require the following additional human health data for use in conducting the regist ration review of Nabam.

860.1520 -- Processed food/feed Special Study -- Migration Study 3 Special Study -- Nature of Residue in Paper 3

For more information, please refer to Nabam: Human Health Risk Assessment Scoping Document in Support of Registration Review , located in the docket.

Product Chemistry Anticipated Data Needs

 The Agency does not anticipate the need to re quire additional product chemistry data for the registration review at this time.

For more information, please refer to Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Registration Review of Nabam , located in the docket.

Incidents:

Ecological:

 No Nabam ecological incidents have been repo rted in the Agency's Ecological Incident Information System (EIIS).

Human Health:

 No Nabam human poisoning incidents have been reported in the Agency's Incident Data System (IDS).

3 The anticipated DCI will provide that a protocol must be submitted for review and approval by the Agency prior to initiating this study.Docket Number: EPA-HQ-OPP-2012-0339 www.regulations.gov

9 of 11 Endangered Species

The Agency has not conducted a risk assessmen t that supports a complete endangered species determination for Nabam. The ecological risk a ssessment planned during registration review will allow the Agency to determine whether Nabam’s use has 'no effect' or 'may affect' federally listed threatened or endangered sp ecies (listed species) or their de signated critical habitats. When an assessment concludes that a pesticide’s use 'm ay affect' a listed species or its designated critical habitat, the Agency will consult with th e U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriate.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its 1996 reregistrati on eligibility decision for nabam, EPA reviewed these data and select ed the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), Nabam is subject to the endocrine screening part of the Endocri ne Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must scre en all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide activ e ingredients and 9 inert ingred ients. Nabam is not among the group of 58 pesticide active ingredients on the in itial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call-ins, requiring the submission of EDSP screening assa ys for Nabam. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 scr eening battery, please visit our website: http://www.epa.gov/endo/.Docket Number: EPA-HQ-OPP-2012-0339 www.regulations.gov

10 of 11 Timeline

EPA has created the following estimated timeline for the completion of the Nabam registration review:

Anticipated Schedule Activities Estimated Month/Year Phase 1: Opening the docket Open Public Comment Period for Docket Completed July 2012 Close Public Comment Peri od for Docket Completed September 2012 Phase 2: Case Development Develop Final Work Plan (FWP) Completed December 2012 Issue DCI December 2013 Data Submission December 2015 Open Public Comment Period for Preliminary Risk Assessments June 2017
Close Public Comment Period for Pre liminary Risk Assessments July 2017 Phase 3: Registration Review Decision Open Public Comment Period for Propos ed Reg. Review Decision December 2017 Close Public Comment Period for Proposed Reg. Review Decision February 2018 Final Decision and Begin Post-Decision Follow-up June 2018 Total (years) 6

Next Steps

A DCI will be developed regarding the data needs listed under the “Risk Assessments and Anticipated Data Needs” section of this document. The Agency expects to issue the DCI in December 2013. Human health and environmental fa te and ecological hazard assessments will be conducted for all uses.Docket Number: EPA-HQ-OPP-2012-0339 www.regulations.gov

11 of 11 Summary of Anticipated Data Requirements – Nabam

The table below summarizes anticipated data needs for the Nabam Case in this document (Final Work Plan), Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Registrati on Review of Nabam, and Nabam: Human Health Risk Assessment Scoping Document in Support of Registration Review.

Guideline Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in months from DCI Receipt)

850.4500 4 Algal Toxicity TGAI and ETU 12

850.4550 4 Cyanobacteria ( Anabeana flos-aquae ) Toxicity TGAI and ETU 12

850.1400 Fish early-life stage toxicity test ETU 12

850.3300 5 Modified activated sludge, respiration inhibition test ETU 12

835.3110 5 Ready Biodegradability TGAI 12

835.3220 5 Porous Pot Test TGAI 12

835.3280 5 Simulation Tests to Assess the Biodegradability of Chemicals Discharged to Wastewater TGAI 12

835.3240 5 Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units TGAI 12

860.1520 Processed food/feed TGAI 24 Special Study 6 Nature of Residue in Paper TGAI 24 Special Study 6 Migration Study TGAI 24

4 Results for studies conducted with nabam and ETU for (i) the freshwater green alga, Selenastrum capricornutum

, (ii) the freshwater diatom, Navicula pelliculosa , (iii) the marine diatom, Skeletonema costatum , and (iv) the cyanobacteria species Anabaena flos-aquae , must be submitted to satisfy this requirement. Final 850 guidelines for the algal testing were posted in June 2012. The Pub lic Draft OPPTS 850.5400 Algal Toxicity guideline was split into two separate guidelines and renumbered with the cy anobacteria species separated into OCSPP 850.4550 and the other three species under OCSPP 850.4500.
5 The results of the Activated Sludge Respiration Inhib ition Test (ASRI) expected to be required will determine which of these three biodegradation tests would be anticipated to be required. If the ASRI test EC50 is less than or equal to 20 mg/L, then either the Biodegradation in Activated Sludge Study or Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or the Porous Pot Test would be anticipated to be required. If the ASRI test EC50 is greater than 20 mg/L, then the DCI expected to be issued would provide that the registrant would choose to conduct either: (i) Ready Biodegradability or (ii) a) Biode gradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or c) the Porous Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing would be expected to be required. If, however, the antimicrobial fails the Ready Biodegradability study, then the Biodegradation in Activated Sludge or Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or the Porous Pot study would be expected to be required.
6 The anticipated DCI will provide that a protocol must be submitted for review and approval by the Agency prior to initiating this study.