Docket Number EPA-HQ-OPP-2013-0598 

www.regulations.gov 

Sodium Meta bisulfite and Sulfur Dioxide Preliminary Work 

Plan 

Registration Review: Initial Docket 

Case Numbers 7019 and 4056 

September 2013 

Approved By: 

G~~ )cu.e~.. P v~~'UA ,:)"") 

Richard P. Keigwin, Jr., Director 

Pesticide Re-evaluation Division 

Date 

Susan Lewis, Acting Director 

Antimicrobials Division 

Date 
Inorganic Sulfites Preliminary Work Plan - Table of Contents 

Overview 

Anticipated Data Needs 

Statutory and Regulatory Authority 

Chemical Facts 

Use and Usage Information 

Recent Actions 

3 

4 

5 

6 

7 

9 

Anticipated Risk Assessments for Registration Review 10 

Timeline 12 

Next Steps 12 

Appendix -Additional Considerations in the Inorganic Sulfites Registration Review 13 

References: 

This Preliminary Work Plan summarizes the Environmental Protection Agency's current position 

based on the following documents: 

1. Registration Review: Preliminary Problem Formulation for Ecological Risk, 

Environmental Fate, Endangered Species, and Drinking Water Assessments for Sulfur 

Dioxide (PC Code 077601) and Sodium Metabisulfite (PC Code 111409). Geoffrey 

Sinclair and Larry Liu. July 23, 2013. 

2. Inorganic Sulfites. Human Health Assessment Scoping Document in Support of 

Registration Review. ldeliz Negron-Encarnacion, Ronnie Bever, and Alexandra LaMay. 

September 11, 2013. 

3. Inorganic Sulfite~ (Sulfur Dioxide and Sodium Bisulfite): Review of Human Incidents. 

Elizabeth Evans and Sha:nna Recore. May 15, 2013. 

4. BEAD Chemical Profile for Registration Review: .Sodium metabisulfite. Michelle Ranville, 

Carl Chen, and Katherine Stebbins. December 7, 2010. 

5. BEAD Chemical Profile for Registration Review: Sulfur Dioxide (07760I). Tara 

Chandgoyal, Rafael Prieto, and Stephen Smearman. April 11, 20 13. 

6. Sodium Metabisulfite Appendix A. October 30, 2009. 

7. Sulfur Dioxide Appendix A. February 5, 2013. 

These and other supporting documents for the inorganic sulfites registration review case may be 

found in the docket EPA-HQ-OPP-2013-0598 at http://www.regulations.gov. 

2 
OVERVIEW 

The docket for sodium metabisulfite and sulfur dioxide is now open, initiating the first public 

comment period for this registration review (docket number EPA-HQ-OPP-20 13-0598). Both 

sodium metabisulfite and sulfur dioxide are registered for use as commodity fumigants. Sodium 

metabisulfite products are formulated as an anhydrous powder contained in semi-sealed pads 

which are added to containers holding grapes prior to shipping; the pads absorb moisture and 

release low levels of sulfur dioxide to inhibit the growth ofthe fungus Botrytis cinerea. Sodium 

metabisulfite is also registered for use in enhanced packaging stickers to control mold and odor 

during shipping of clothing, purses, and other commodities. Sulfur dioxide products are 

formulated as gas and as compressed liquid that converts to gas upon release for post-harvest 

grape fumigation in cold-storage warehouses, trucks, vans, trailers, and rail cars (also for control 

of Botrytis cinerea). Sulfur dioxide is also registered for use in the fumigation of barrels and 

corks used in wine production. There are no registered residential uses of either active 

ingredient. This Preliminary Work Plan (PWP) document explains what EPA's Office of 

Pesticide Programs knows about sodium metabisulfite and sulfur dioxide, highlighting 

anticipated data and assessment needs, identifying the types of information that would be 

especially useful to the Agency in conducting the review, and providing an anticipated timeline 

for completing the registration review for sodium metabisulfite and sulfur dioxide. 

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The Agency intends, by sharing this information in the 

docket, to inform the public of what it knows about sodium metabisulfite and sulfur dioxide and 

what types of new data or other information would be helpful for the Agency to receive as it 

moves toward a decision on sodium metabisulfite and sulfur dioxide. The Agency encourages 

all interested stakeholders to review the PWP and Appendix and to provide comments and 

additional information that will help the Agency's decision-making process for these chemicals. 

In addition to general areas on which persons may wish to comment, there are some areas 

identified in the PWP and Appendix about which the Agency specifically seeks comments and 

information. Interested stakeholders could include: environmental non-profit or interest groups; 

pesticide manufacturers; agricultural labor or commodity groups; commercial, institutional, 

residential, and other users of pesticides; or the public at large. 

The Preliminary Work Plan begins by listing the anticipated data needs for sodium metabisulfite 

and sulfur dioxide. Next, it discusses the statutory and regulatory authority for Registration 

Review. Then the document provides chemical facts, use and usage information, recent actions, 

the anticipated risk assessments, and a projected registration review timeline for sodium 

metabisulfite and sulfur dioxide. Finally, the Appendix to this document includes identification 

and discussion of some areas that are considered generally in Registration Review along with 

some additional chemical case-specific information. 

3 
ANTICIPATED DATA NEEDS 

Table 1 below summarizes anticipated data needs for sodium metabisulfite and sulfur dioxide. 

For additional discussion of the anticipated data needs, see the Registration Review: Preliminary 

Problem Formulation for Ecological Risk, Environmental Fate, Endangered Species, and 

Drinking Water Assessments for Sulfur Dioxide (PC Code 077601) and Sodium Metabisulfite 

(PC Code 111409) and Inorganic Sulfites. Human Health Assessment Scoping Document in 

Support of Registration Review. 

Table 1: Anticipated Data Needs for Sodium Metabisulfite and Sulfur Dioxide 

Registration Review 

Estimated 

Guideline Timeframe 

Number Study Title 

Test Material (Months from 

receipt of DCI) 

860.1500 Crop field trials-post-harvest fumigation 1 Sulfur dioxide, 24 TEP 

875.1400 Applicator- inhalation indoor exposure 

Sulfur dioxide, 24 TEP 

875.1700 Product use information Sulfur dioxide, 12 TEP 

875.2500 Post application- inhalation indoor exposure 

Sulfur dioxide, 24 TEP 

Non- A vi an acute inhalation toxicity study with Sulfur dioxide, 24 guideline bobwhite quail TGAI 

Non- Honeybee acute vapor phase Sulfur dioxide, 24 

guideline TGAI 

Non- Vegetative vigor vapor phase Sulfur dioxide, 12 

guideline TEP 

Non- Monitoring data on fumigated commodities (from Sodium 

metabisulfite, 24 

guideline sodium metabisulfite pads) TEP 

TGAJ = techmcal grade active mgredient; TEP = typ1cal end-use product 

Additional information needs: 

Current labels do not have clear application information such as maximum single application 

rate, maximum number of applications per year, and minimum application interval. Additional 

information on typical number of applications and application intervals in storage and shipping 

would also be helpful. Some sodium metabisulfite labels specify that grapes can be fumigated 

with gaseous sulfur dioxide and then subsequently transported with sodium metabisulfite pads. 

Other labels do not specify if use of sulfur dioxide gas and sodium metabisulfite pads can be 

combined. In the absence of clear label information, the Agency will make conservative 

assumptions in the risk assessment. In addition, the RED required label language regarding 

1 In lieu of data, modified application parameters may be proposed on the sulfur dioxide product labels. 

4 
limits on the concentration of sulfur dioxide released into the atmosphere during aeration- this 

language does not appear on some of the sulfur dioxide end-use product labels. During 

registration review, the Agency will work with registrants to revise the sodium metabisulfite and 

sulfur dioxide product labels. 

STATUTORY AND REGULATORY AUTHORITY 

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States (U.S.) generally must be registered by the 

Environmental Protection Agency (EPA or the Agency), based on scientific data showing that 

they will not cause unreasonable risks to human health or the environment when used as directed 

on product labeling. The registration review program is intended to make sure that, as the ability 

to assess risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects to human health or the 

environment. Changes in science, public policy, and pesticide use practices will occur over time. 

Through the registration review program, the Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program is provided on EPA's website.2 

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to detennine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration review begin at 40 CFR 155.40. The 

Agency will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

Agency's opportunity to state what it knows about the pesticide and what additional risk analyses 

and data or information it believes are needed to make a registration review decision. After 

reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for 

the registration review of sodium metabisulfite and sulfur dioxide. 

2 http://www.epa.gov/oppsrrd 1/registration_review/ 

5 
CHEMICAL FACTS 

Tables 2 and 3 provide a summary of the chemical facts for sodium metabisulfite and sulfur 

dioxide. 

Table 2: Chemical Facts for Sodium Metabisulfite 

PC code 111409 

Case Number 7019 

CAS Number 7681-57-4 

Year first registered 1989 

Pesticide Type Fungicide 

Chemical class Inorganic 

Reregistration Eligibility May 2007 

Decision (RED) 

Tolerance Reassessment Not applicable 

Eligibility Decision 

(TRED) 

Cumulative group Sodium metabisulfite has not been identified as a member of a 

cumulative group that shares a common mechanism of toxicity. 

40 CFR Citation Tolerances are established in 40 CFR § 180.444 under sulfur 

dioxide. 

Dual-use In addition to its conventional use in packaging for stored grapes, 

sodium metabisulfite is embedded in packaging stickers to inhibit 

odor causing bacteria and mold/mildew growth in commercial 

goods such as footwear, clothing, luggage, handbags, purses, 

wallets, furniture, and the like. 

Non-pesticidal uses Sodium metabisulfite is used as a preservative and antioxidant in 

food and in wine and beer making. It is also used in photography, 

in tree stump removal, in wastewater treatment, in water 

desalination, and in testing for sickle cell anemia. 

Pesticide Re-evaluation Khue Nguyen, nguyen.khue@epa.gov, 703-347-0248 

Division, Chemical 

Review Manager 

Antimicrobial Division, Jaclyn Pyne, pyne.jaclyn@epa.gov, 703-347-0213 

Chemical Review 

Manager 

Registration Division, Tony Kish, kish.tony@epa.gov, 703-308-9443 

Product Manager 

Table 3: Chemical Facts for Sulfur Dioxide 

PC code 077601 

Case Number 4056 

CAS Number 7446-09-5 

Year first registered 1948 

Pesticide Type Fungicide 

6 
Table 3: Chemical Facts for Sulfur Dioxide 

Chemical class Inorganic 

Reregistration Eligibility May 2007 

Decision (RED) 

Tolerance Reassessment Not applicable 

Eligibility Decision 

(TRED) 

Cumulative group Sulfur dioxide has not been identified as a member of a cumulative 

group that shares a common mechanism of toxicity. 

40 CFR Citation Tolerances for sulfur dioxide are established in 40 CFR § 180.444. 

Dual-use Sulfur dioxide is registered for conventional pesticidaJ uses only 

and has no registered antimicrobial or biopesticidal uses. 

Non-pesticidal uses Sulfur dioxide is used in foods (especially dried fruits) as a 

preservative and in beverages (especially wine) as an antioxidant 

and preservative. It is also used as a reducing agent in municipal 

wastewater treatment to treat chlorinated wastewater prior to 

release. 

Pesticide Re-evaluation Khue Nguyen, nguyen.khue(ci'cpa.gov, 703-347-0248 

Division, Chemical 

Review Manager 

Registration Division, Tony Kish, kish.tonvt@cpa.gov, 703-308-9443 

Product Manager 

USE AND USAGE INFORMATION 

Tables 4 and 5 summarize the use and usage information for sodium metabisulfite and sulfur 

dioxide. Please see the BEAD Chemical Profile for Registration Review: Sodium metabisulfite 

and BEAD Chemical Profile for Registration Review: Sulfur Dioxide (077601) in the registration 

review docket for more details. 

Table 4: Sodium Metabisulfite Pesticidal Use and Usage Information 

Summary of Use Registered for use for postharvest treatment of grapes to treat 

Botrytis cinerea which causes gray mold. Also registered for use as 

an antibacterial and antifungal agent in clothing, leather goods, and 

other commercial products. 

Use Sites Grapes, clothes storage, furniture, athletic equipment, carpets, 

leather products, human bedding, human clothing, and human 

footwear. 

Summary of Usage The Agency only has usage information for California, which 

accounts for about 90% of national grape production. 

Approximately l ,759 lbs of sodium metabisulfite were applied to 

domestic grapes in California in 2008. Many grapes imported from 

Central and South America use sodium metabisulfite pads; the 

Agency lack definitive usage information on imported grapes. The 

7 
Table 4: Sodium Metabisulfite Pesticidal Use and Usage Information 

Agency also lacks usage information for sodium metabisulfite's 

antimicrobial use as packaging stickers. 

Formulation Type(s) Semi-sealed pads/bags and stickers impregnated with sodium 

metabisulfite. 

Application Method(s) Pads/bags are placed inside containers of fresh grapes and release 

sulfur dioxide as moisture is absorbed; stickers are placed in 

commercial goods 

Technical Registrant(s) There are no technical registrants; end-use product registrants are: 

Imal LTDA, Productos Quimicos y Alimenticios OSKU S.A., 

Quimetal Industrial S.A., Grapetek (PTY) LTD, Embalajes Proem 

LTDA., Insumos Fruticolas S.A. Infruta, Materiales de Embalaje 

S.A., Quimas S.A., and Micro-Pak LTD 

No. of Registrations 12 

Restricted Use No 

Table 5: Sulfur Dioxide Pesticidal Use and Usage Information 

Summary of Use Registered for use for post-harvest fumigation of grapes held in 

cold storage, fumigation trailers, railcars, transport vehicles, and 

warehouses to treat Botrytis cinerea which causes gray mold. Also 

registered for use in combination with carbon dioxide to treat for 

black widow spider on grapes in warehouse settings. 

Use Sites Grapes in railroad boxcars, trucks, truck trailers, transport vehicles, 

warehouses, storage rooms, and fruit storage rooms; wine barrels 

and corks 

Summary of Usage The Agency only has usage information for California, which 

accounts for about 90% of national grape production. 

Approximately 89,578 lbs of sulfur dioxide were used on domestic 

wine and non-wine grapes in California in 2010. Use seems to be 

increasing. In 201 1, about 62,481 lbs of sulfur dioxide were used 

on domestic table grapes and 69,290 lbs were used on domestic 

wine grape. Many grapes imported from Central and South 

America are treated with sulfur dioxide; the Agency lack definitive 

usage information on imported graQ_es. 

Formulation Type(s) Pressurized gas containers; pressurized liquid containers 

Application Method(s) Pressurized containers release sulfur dioxide as a gas 

Technical Registrant(s) There are no technical registrants; end-use product registrants are: 

Sierra Chemical Co., Snowden Enterprises, Inc., and Seaco 

Technologies, Inc. 

No. of Registrations 3 

Restricted Use No 

Guidance for Commenters: Additional areas of use and usage related information 

requested for this registration review, and of particular interest to EPA, are described below. 

8 
• The Agency has limited use and usage data on sodium metabisulfite and sulfur dioxide 

from the California Department of Pesticide Regulation. The Agency seeks other known 

uses of sodium metabisulfite and sulfur dioxide in states other than California and in 

other countries from which grape commodities are imported into the USA. 

• The Agency seeks usage information on sodium metabisulfite use as an antimicrobial in 

packaging stickers. 

• Certain sodium metabisulfite and sulfur dioxide labels are unclear with respect to 

application parameters such as the size of the treated area, retreatment intervals, or 

maximum annual application rates. Without further information, EPA expects to use 

conservative assumptions to approximate these parameters in order to conduct a 

quantitative risk assessment. However, the Agency will work with registrants to clarify 

information on product labels. 

• Confirmation of the following label information: sites of application; formulations; 

application methods and equipment; maximum application rates and application 

intervals; PPE requirements. 

• State or local use restrictions. 

• Foreign technical registrants not listed above who supply technical sodium metabisulfite 

and sulfur dioxide to the US market. 

RECENT ACTIONS 

In June 2013, the Agency received a petition for an exemption from a requirement of a tolerance 

for residues of sodium metabisulfite when used as a pesticide inert ingredient (78 FR 33788). 

A new use for sodium metabisulfite formulated as enhanced packaging stickers was added in 

March 2013. 

In September 2011, the Agency established a 10 ppm time-limited tolerance for residues of 

sulfur dioxide in or on figs. This was related to an emergency exemption which was granted for 

use of sulfur dioxide to control grey mold on California figs. This tolerance expires on 

December 31 ,2014 (76 FR 56644). 

9 
ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW 

The most recent comprehensive human health risk assessment for sodium metabisulfite and 

sulfur dioxide was completed in 2007 in preparation for the Reregistration Eligibility Decision. 

The most recent ecological and environmental fate risk assessment was completed in 2007 for 

the same purpose. Findings and conclusions from these risk assessments are summarized in the 

Registration Review: Preliminary Problem Formulation for Ecological Risk, Environmental 

Fate, Endangered Species, and Drinking Water Assessments for Sulfur Dioxide (PC Code 

077601) and Sodium Metabisulfite (PC Code 111409) and Inorganic Sulfites. Human Health 

Assessment Scoping Document in Support of Registration Review. 

During registration review, the Agency anticipates the need to conduct a comprehensive 

ecological risk assessment, including an endangered species assessment, for all uses of sodium 

metabisulfite and sulfur dioxide. For human health, EPA anticipates the need to conduct a new 

bystander exposure assessment and occupational handler risk assessment during registration 

review. EPA also intends to work with FDA to determine residue levels in various foods and 

appropriate methods for assuring safe levels of sulfite residues from pesticidal applications in 

foods. If toxicological endpoints or points of departure are revised based on the data that are 

anticipated to be required for registration review, they will be considered in the new assessments, 

as well as any changes to the standard operating procedures or default exposure assumptions. 

Table 6 below summarizes the anticipated registration review risk assessments based on the 

EFED Problem Formulation and HED Scoping Document. 

Table 6: Anticipated Risk Assessments for Sodium Metabisulfite and Sulfur Dioxide Registration 

Review 

Type of Risk Assessment Conduct? Notes 

Ecological and Environmental Fate 

Comprehensive ecological y 

(species to be assessed 

include terrestrial and aquatic 

organisms), including 

endangered species 

Incidents Will check for No ecological incidents have been identified 

updates involving either sodium metabisulfite or sulfur 

dioxide. 

Human Health 

Dietary 

Food y The Agency will work with FDA to determine 

pesticidal residue levels in foods and appropriate 

methods for assuring safe levels in dietary 

consumption. 

Drinking water N The Agency does not have any drinking water 

concerns for sodium metabisulfite and sulfur dioxide. 

Occupational 

10 
Handlers (mixers, loaders, y There is potential for occupational applicator 

applicators) inhalation exposure to sulfur dioxide during 

fumigation. 

Post -application y Potential exposure due to off-gassing are anticipated 

to be assessed for workers conducting postapplication activities near treatment operations. 

Residential 

Handlers N Sodium metabisulfite and sulfur dioxide are not 

Post-application N registered for residential use; therefore, residential 

handler and residential post-application assessments 

are not applicable. 

Bystander y There is potential for bystander exposure from 

offgassing during grape fumigations which involve 

the release of high levels of su[fur dioxide during 

aeration. 

Other 

Aggregate N Evaluates the combined risk from dietary and 

residential exposures. An aggregate assessment 

would include only the dietary exposure scenarios, for 

which quantification of risks is not appropriate since 

exposure is primarily through inhalation. 

Cumulative N Sodium metabisulfite and sulfur dioxide have not 

been identified as members of a cumulative group that 

share a common mechanism of toxicity. 

Tolerances N There are currently no established Codex, Canadian, 

and/or Mexican MRLs for sulfur dioxide in/on grapes, 

therefore tolerance harmonization is not applicable. 

Incidents Will check for For a discussion of reported human incidents for 

updates sodium metabisulfite and sulfur dioxide, see page 11 

of the Scoping Document and the Inorganic Su(fites 

(Sulfur Dioxide and Sodium Bisulfite): Review of 

Human Incidents. 

Guidance for Commenters: 

Additional ecological information requested for this registration review, and of particular 

interest to EPA, is described below. 

• Ecotoxicity data from the published literature. 

• Information on the maximum application rate, the maximum number of applications, 

and/or the minimum application interval as well as the typical number of applications and 

application intervals. 

• Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency. 

11 
Additional human health information requested for this registration review, and of particular 

interest to EPA, is described below. 

• The Agency requests relevant published toxicity data for sulfur dioxide. The Agency 

recommends that registrants present a weight-of-evidence rationale summarizing why use 

of published data will suffice for endpoint selection to determine risks from exposure to 

sulfur dioxide gas through inhalation. 

TIMELINE 

EPA has created the following estimated timeline for the completion of the sodium metabisulfite 

and sulfur dioxide registration review in Table 7 below. 

Table 7: Projected Sodium Metabisulfite and Sulfur Dioxide Registration Review Timeline 

Activities Estimated Date 

Opening the Docket 

Open Docket and 60-day Public Comment Period 20 13 - September 

Close Public Comment 2013 -November 

Case Development 

Final Work Plan 2014 - February 

Issue DCI 2014 April - June 

Data Submission 2016 April - June 

60-day Public Comment Period for Draft Risk Assessmentsj 2017 October - December 

Registration Review Decision 

60-day Public Comment Period for Proposed Registration 2018 April - June 

Review Decision 

Registration Review Decision and Begin Post-Decision 2019 

Follow-up 

Total (years) 6 

NEXT STEPS 

After the 60-day public comment period closes, the Agency will review and respond to any 

comments. received in a timely manner and then issue a Final Work Plan for the registration 

review of sodium metabisulfite and sulfur dioxide. 

3 The regulations governing Registration Review generally require the Agency to provide a public comment period 

of at least 30 calendar days for draft risk assessments; see 40 CFR Part l55.53(c). For conventional pesticides, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments. 

12 
Appendix- Additional Areas Considered in the Sodium Meta bisulfite and 

Sulfur Dioxide Registration Review 

PUBLIC COMMENTS AND FEEDBACK: 

Guidance for Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

be of particular use. 

Environmental Justice: 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to sodium metabisulfite or sulfur dioxide compared to the 

general population. Please comment if you are aware of any sub-populations that may have 

atypical, unusually high exposure compared to the general population. 

ENDANGERED SPECIES: 

A risk assessment that supports a complete endangered species determination has not been 

conducted for sodium metabisulfite and sulfur dioxide: The ecological risk assessment planned 

during registration review will allow the Agency to determine whether use of sodium 

metabisulfite and sulfur dioxide have "no effect" or "may affect" federally listed threatened or 

endangered species (listed species) or their designated critical habitats. When an assessment 

concludes that a pesticide's use "may affect" a listed specjes or its designated critical habitat, the 

Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries 

Service (the Services), as appropriate. 

ENDOCRINE DISRUPTOR SCREENING PROGRAM: 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive-effects in different 

taxonomic groups. As part of its most recent registration decision for sodi urn metabisulfite and 

sulfur dioxide, EPA reviewed these data and selected the most sensitive endpoints for relevant 

risk assessment scenarios from the existing hazard database. However, as required by FFDCA 

section 408(p), sodium metabisulfite and sulfur dioxide are subject to the endocrine screening 

part of the Endocrine Disruptor Screening Program (EDSP). 

13 
EPA has developed the EDSP to determine whether 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 other such endocrine effects as the Administrator 

may designate." The EDSP employs a two-tiered approach to making the 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 estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and theE, A, or T effect. 

Under FFDCA section 408(p ), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 20134 and includes some 

pesticides scheduled for Registration Review and chemicals found in water. For further 

information on the status of the EDSP, the policies and procedures, the lists of chemicals, future 

lists, the test guidelines and the Tier 1 screening battery, please visit our website.5 · 

In the interim, EPA is making no human health or environmental safety findings associated with 

the EDSP screening of sodium metabisulfite and sulfur dioxide. Before completing this 

Registration Review, the Agency will make an EDSP FFDCA section 408(p) determination. 

HUMAN STUDIES: 

The Agency is aware that inorganic sulfites studies involving human subjects are available in the 

scientific literature. The 2007 RED referenced regulatory levels established by other agencies 

which are based on studies that involved intentional exposure of human subjects. In addition, 

· OPP may be coordinating with other agencies on the human health risk assessment for sodium 

metabisulfite and sulfur dioxide. If after considering any of these studies and/or any submitted 

by the registrants, the EPA decides to rely on one or more of them, the Agency will ensure that 

all regulatory requirements are met, including EPA ethics reviews or Human Studies Review 

Board reviews of any data from research involving intentional exposure of human subjects. 

4 See http://www.regulations.gov/#!documentDetaii;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals. 

5 http://www.epa.gov/endo/ 

14