UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: September 11, 2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Inorganic Sulfites. Human Health Assessment Scoping Document in Support of 

Registration Review. 

PC Code: 077601 and 111409 DP Barcode: D411 060 

Decision No.: 477567 Registration No.: NA 

Petition Nos.: NA Regulatory Action: Registration Review 

Risk Assess Type: Scoping Document CaseNo.: NA 

TXRNo.: NA CAS No.: 7681-57-4 and 7446-09-5 

MRIDNo.: NA 

FROM: 

THRU: 

TO: 

Ideliz Negron-Encarnacion, Ph.D., Chemis}? _ ??< L-1 Ronnie Bever, Ph.D., Toxicologist ~~1 Alexandra LaMay, M.Sci., Biologist U 

Risk Assessment Branch V 

Health Effects Division (7509P) 

Michael Metzger, Branch Chief / IJ j}) Risk Assessment Branch V ~/1 ?t ~ / 

Jeffrey Dawson, Chemist 

Immediate Office 

Health Effects Division (7509P) 

Khue Nguyen, Risk Manager Reviewer 

Neil Anderson, Branch Chief 

Risk Management & Implementation Branch VII 

Pesticide Re-evaluation Division (7508P) 

Page 1 of25 
EXECUTIVE SUMMARY 

EPA's Health Effects Division (HED) has evaluated the available data and the most recent 

human health risk assessments for the inorganic sulfites (i.e. sulfur dioxide and sodium 

metabisulfite (an S02 generator)) to determine the scope of work necessary to support the 

registration review process. HED has considered the current use patterns (OPPIN Database and 

current labels) as well as the available toxicity and exposure information for the inorganic 

sulfites. The inorganic sulfites are fungicides used to treat botrytis cinerea, the fungus which 

causes bunch rot, or gray mold on grapes. In addition, sulfur dioxide may be used for sanitation 

of wine corks and barrels, and for the control of botrytis cinerea in figs. Other sources of sulfites 

include uses in alcohol regulated by the Alcohol and Tobacco Tax and Trade Bureau, and uses as 

food additives and as components of pharmaceuticals regulated by the Food and Drug 

Administration (FDA). 

Toxicity /Hazard 

The two chemicals, sulfur dioxide (inhalation exposure) and sulfites (such as sodium 

metabisulfite, a metabolite resulting in dietary exposure) have distinct toxicities. The Agency 

toxicological databases for sulfur dioxide and sodium metabisulfite) lack any OPP HED studies. 

However, there is a large volume of published data detailing the toxicity of sulfur dioxide, not 

only in animals but also in humans, including sensitive subpopulations of humans. HED 

guideline studies may not be necessary to support registration review. Rather, for sulfites, the 

HED will consider the results of an assessment of clinical human data currently in progress at the 

Food and Drug Administration (FDA). Therefore, at this time the Agency is requesting no new 

toxicity data. For sulfur dioxide, the HED recommends that registrants submit relevant, 

published toxicity studies and present a compelling weight-of-evidence rationale summarizing 

why use of the data from these studies will suffice for endpoint selection to determine risks from 

exposure to sulfur dioxide gas through inhalation. Because these published articles are not 

currently available to the Agency, they have not been reviewed by HED yet, and only a summary 

of the toxicity is provided below. 

Sulfur Dioxide: The primary mechanism of action of sulfur dioxide is that of an irritant, the 

lungs being the most sensitive organ. Lung effects can be observed after acute exposure, and the 

time of peak effect is 5-l 0 minutes. The most sensitive endpoints are increased airway resistance 

(sRaw) and decreased forced expiratory volume in 1 second (FEV 1). Asthmatics are the 

sensitive group to sulfur dioxide exposure, and exercise (promoting mouth-breathing) 

exacerbates this effect. Sulfur dioxide is considered not classifiable (Group 3) as to 

carcinogenicity by IARC (1992). No adverse effect was reported at any dose on the 

musculoskeletal, hepatic, renal, or endocrine systems or body weight in humans. Toxicological 

studies provide very little biological plausibility for reproductive outcomes related to so2 

exposure. It is unclear if durations of treatment longer than 5-l 0 minutes will increase the 

severity of the symptoms. 

Inorganic Sulfites: In general, symptoms in sulfite-sensitive humans (atopic population) to oral 

ingestion of sulfites include flushing, tingling, pruritis, dysphagia, chest pain, urticaria, 

angioedema, acute broncho-constriction, hypotension, anaphylactic shock, and loss of 

consciousness. It has been stated that broncho-constriction is the most commonly reported 

Page 2 of25 
Page 3 of 25

adverse reaction to sulfites in a sub-group of asthmatic subjects. Data indicate that the current 

regulatory standard of 10 ppm of sulfites in/on grapes and figs is protective, even for the 

sensitive population.

Residue Chemistry

Tolerances are established in the 40 CFR §180.636 for residues of sulfites in/on grapes and figs. 

The tolerance expression needs to be modified according to the Interim Guidance on Tolerance 

Expressions (S. Knizner, 27/May/2009). For sulfur dioxide end-use products, residue data 

depicting the label use pattern may be required. Alternatively, modified use pattern supported by 

the available residue chemistry data may be proposed. In addition, labels issues may need to be 

addressed such as inclusion of a statement restricting use of both, sulfur dioxide pads and 

fumigation with gaseous sulfur dioxide, in products that are currently silent with this respect. 

Dietary Exposure

Sulfites are the residues of concern for consumption of grapes and figs. Other sources of sulfites 

in/on food are regulated by other agencies. The Food and Drug Administration (FDA) is 

currently undergoing an effort to prepare a dietary risk assessment considering several sources of 

exposure to sulfites in food. The EPA will work with the FDA in order to address the dietary 

exposure of sulfites. 

Aggregate Risk Assessment

Exposure to sulfites is expected to occur mainly through the oral (dietary) route; dermal and 

inhalation exposure will be insignificant. Based on this, the aggregate assessment includes only 

the dietary exposure scenario. 

Exposure to sulfur dioxide is primarily through inhalation; significant oral and dermal exposures 

are not expected. Additionally, the inhalation endpoint for sulfur dioxide is different from that 

for the ingested sulfite residues. Based on this, bystander exposure to sulfur dioxide would not 

be aggregated with other routes of exposure. 

Occupational & Residential Exposure

Sulfur dioxide and sodium metabisulfite are not registered for residential uses. However, 

bystander exposure to SO2 may occur as a result of offgassing from sulfur dioxide fumigation 

inside warehouses and transportation vehicles. Bystander risk will need to be evaluated 

depending on the information to be provided by registrants with regard to sulfur dioxide 

emissions and the label prescribed use conditions. Fumigation use information is also required 

under Registration Review for assessment of potential buffers for aeration of enclosed spaces. 

There is potential for occupational applicator exposure to sulfur dioxide during fumigation. Data 

to address potential occupational applicator exposures are required under registration review. An 

updated occupational handler risk assessment may be required during registration review based 

on exposure and/or toxicity data. There is potential for occupational post-application exposure to 

sulfur dioxide while handling treated commodities or in facilities after fumigation. Data 

addressing potential exposures due to off-gassing from treated facilities/commodities for workers 

conducting post-application activities need to be submitted to the Agency. A new occupational 

post-application assessment may be required under registration review based on exposure and/or 

toxicity information.
Page 4 of 25

1.0 INORGANIC SULFITES FORMULATIONS AND USE PATTERNS 

HED used the Biological and Economics Analysis Division (BEAD) Label Data System to 

identify all agricultural and non-agricultural uses of sulfur dioxide and sodium metabisulfite. See 

the BEAD Label Data Reports for sulfur dioxide (02/05/2013) and sodium metabisulfite

(10/30/2009) for a complete list. In addition, the BEAD Chemical Profile for Registration 

Review was used to characterize the use patterns of sulfur dioxide (04/11/2013, T. Chandgoyal 

et.al.) and sodium metabisulfite (12/07/2010, M. Ranville et. al.). These products are used as a 

postharvest treatment for grapes to control gray mold disease which is caused by botrytis 

cinerea. In addition, sulfur dioxide is used in the wine industry for the sanitation of corks and 

barrels, and an emergency exception is in place for the use of sulfur dioxide to control botrytis 

cinerea in figs.

Products containing sulfur dioxide as the active ingredient are formulated as liquid under

pressure (99.9- 100% sulfur dioxide) which turns into gas upon release of pressure. Sulfur 

dioxide is registered for post-harvest fumigation of grapes held in cold storage in enclosed spaces

(e.g. trailers, railcars, transportation vehicles and warehouses). 

Sodium metabisulfite products are composed of anhydrous solid active ingredient. When 

anhydrous sodium metabisulfite products absorb moisture from air, they produce sulfur dioxide 

gas. Semi-sealed pads or bags impregnated with sodium metabisulfite (concentrations vary from 

8.6 - 98.5% a.i.) are placed inside storage and shipment containers of fresh grapes. The pads 

release sulfur dioxide up to 1-5 ppm within the containers as they absorb moisture (EPA, 2007). 

Based on a focus meeting with the registrants (04/30/2013) of sulfur dioxide and sodium 

metabisulfite end-use products, the former is used on grapes/figs produced in the USA for 

domestic consumption while the latter is mainly used for grapes to be imported to the USA for 

domestic consumption. In addition, the sodium metabisulfite pads may be used for grapes 

produced in the USA and exported to other countries. 

Conclusions: Label statements were specified in the 2007 RED for sulfur dioxide and sodium 

metabisulfite end-use products. It is noted that limits to the sulfur dioxide concentration released 

to the atmosphere during aeration were included in these label statements recommended in the 

RED, see Appendix D. These limits should be included on the labels of sulfur dioxide end-use 

products. An initial fumigation with sulfur dioxide followed by the use of pads is recommended 

on the label of some sodium metabisulfite pads only. The labels of other end use products 

formulated with sodium metabisulfite and sulfur dioxide are silent. During registration review 

label revisions may be addressed by inclusion of a statement on the label of these products 

indicating that the combined use of pads and fumigation with sulfur dioxide is not allowed. In 

addition, label revisions may be proposed by HED during registration review as part of 

harmonization efforts within inorganic sulfite end-use products and revisions to all fumigant 

labels.
Page 5 of 25

2.0 HAZARD IDENTIFICATION/TOXICOLOGY

The Agency toxicological database for sulfur dioxide and inorganic sulfites lacks any OPP HED 

studies. However, there is a large volume of published data detailing the toxicity of sulfur 

dioxide, not only in animals but also in humans, including sensitive sub-populations of humans. 

HED guideline studies may not be necessary to support registration review. Rather, for sulfites,

the HED will consider the results of an assessment of clinical human data currently in progress at 

the Food and Drug Administration (FDA). Therefore, at this time the Agency is not requesting 

new toxicity data. For sulfur dioxide, the HED recommends that registrants submit relevant, 

published toxicity data and present a compelling weight-of-evidence rationale summarizing why 

use of the data from these studies will suffice for endpoint selection to determine risks from 

exposure to sulfur dioxide gas through inhalation (see HASPOC memo; 05/21/2013). A

summary of the toxicity of the literature studies in the OPP HED database is provided below.

Sulfur dioxide is a gas to which humans may be exposed primarily via the inhalation route. 

Sulfite residues can accumulate in/on grapes and figs leading to oral exposure. As explained 

below, inhalation and oral exposure result in differing toxic syndromes. 

Sulfur dioxide: The primary mechanism of action of sulfur dioxide is that of an irritant. On 

contact with moist mucous membranes, sulfur dioxide produces sulfurous acid, which is a direct 

irritant and inhibits mucociliary transport. The irritant induced stimulation of airway sensory 

end organs causes vagal stimulation and airway smooth muscle contraction. The most sensitive 

organ system to the gas is the lungs; however, eye and dermal irritation may result at higher 

concentrations. Effects in the respiratory system can be observed after acute exposure, and the 

time of peak effect is 5-10 minutes. The most sensitive endpoints are increased airway resistance 

(sRaw) and decreased forced expiratory volume in 1 second (FEV1). An increase of 100% in 

sRaw or 15% in FEV1 is considered adverse. 

Asthmatics are the sensitive group to sulfur dioxide exposure, and exercise (promoting mouthbreathing) exacerbates this effect. Exercising asthmatics may be adversely affected at very low 

concentrations of sulfur dioxide. These effects on FEV1and sRaw can be apparent in laboring 

asthmatics at concentrations as low as 0.2 ppm. Exposure of the general population to 20 ppm

sulfur dioxide can result in respiratory system irritation, decreased lung function, airway 

inflammation, enhanced airway hyper-responsiveness, irritation of skin and eyes, and clastogenic 

effects in humans. 

Sulfur dioxide is considered not classifiable (Group 3) as to carcinogenicity by IARC (1992). 

No adverse effect was reported at any dose on the musculoskeletal, hepatic, renal, or endocrine 

systems or body weight in humans. Epidemiologic studies on birth outcomes have observed 

positive associations between sulfur dioxide (SO2) exposure and low birth weight; however, 

toxicological studies provide very little biological plausibility for reproductive outcomes related 

to SO2 exposure. The inconsistent results across trimesters of pregnancy and the lack of 

evidence regarding confounding by co-pollutants further limit the interpretation of these studies. 

Currently, the most sensitive endpoint occurs in laboring asthmatics during acute exposure (peak 

effect at 5-10 minutes); it is unclear if longer durations of treatment will increase the severity of 
Page 6 of 25

the symptoms (i.e. result in a lower point of departure). Because sulfur dioxide is a gas and 

endpoints for inhalation exposure are expected to be protective of dermal effects, dermal risk 

will not be assessed during registration review.

Sulfite residues: The FDA requires ingredient labels to list sulfite concentrations in excess of 

10 ppm (expressed as SO2); however, both sulfur dioxide (21CFR 182.3862) and sodium 

metabisulfite (21CFR 182.3766) are listed as Generally Recognized As Safe (GRAS) by the 

FDA, with limitations, as food preservatives. The provocative dose level established by the FDA 

is 3.7 mg sulfite (or 5 mg sulfite salt), which they do not anticipate to cause a hazard to health. 

At 3.7-10 mg sulfite, the FDA does not expect an acute, life-threatening, anaphylactic-like 

reaction. Sulfite-sensitive individuals would not experience more than a moderate acute 

sensitivity reaction. At greater than 10 mg sulfite, a severe anaphylactic type of reaction may 

occur in sulfite-sensitive individuals. The 3.7 mg sulfite dosage may be achieved by consuming 

about 1 pound of grapes with a sulfite tolerance level of 10 ppm. However, this dosage was set 

based on liquid bolus or capsular administration with the response measured within 15 minutes. 

It is unlikely that anyone would consume a pound of grapes within 15 minutes, particularly if 

adverse symptoms are developing. In general, symptoms in sulfite-sensitive humans include 

flushing, tingling, pruritis, dysphagia, chest pain, urticaria, angioedema, acute bronchoconstriction, hypotension, anaphylactic shock, and loss of consciousness. It has been stated that 

broncho-constriction is the most commonly reported adverse reaction to sulfites in a sub-group 

of asthmatic subjects.

There is a subpopulation of humans that demonstrate hypersensitivity to sulfites (atopic 

population). The reaction to sulfite residues can be particularly severe in hypersensitive 

individuals who are also asthmatics, because the reaction can trigger an asthma attack. Data 

indicate that the current regulatory standard of 10 ppm (a residue level common to that naturally 

occurring in many foods) is protective, even for the sensitive population.

3.0 RESIDUE CHEMISTRY

The inorganic sulfites scoping document includes the chemicals sulfur dioxide and sodium 

metabisulfite. The latter liberates sulfur dioxide in humid conditions which is the compound 

responsible for the pesticidal activity. The nomenclature, registration numbers, PC Code and 

chemical structure of sulfur dioxide and sodium metabisulfite are listed in Appendix B. 

The nature of the residue in grapes is adequately understood based on metabolism studies in 

which grapes were treated with radiolabel sulfur dioxide once per week for 16 weeks (J.R. 

Tomerlin, D344469, 10/09/2007 and B. Cropp-Kohlligian, D185546, 09/08/1993). Sulfite and 

sulfate were identified as the main residues in/on grapes treated with sulfur dioxide. Sulfate is a 

natural constituent in the human body and is necessary for the biosynthesis of sulfur-containing 

compounds. The main sources of sulfate are food (due to food additive uses) and drinking water. 

A study reported residues of sulfate in food and beverages at levels up to 4.9 mg/g in dried 

apples and 500 mg/L in coconut milk (IMNA 2004). Based on the ubiquitous nature of sulfate, 

its nutrient characteristics, and the low level of sulfate expected in/on grapes, it is not considered 

a residue of concern. 
Page 7 of 25

As stated in the 2007 RED, the Food and Drug Administration (FDA) required ingredient labels 

to list sulfite concentrations in excess of 10 ppm (expressed as SO2) in order to protect sulfite 

sensitive individuals. For the registration of the sodium metabisulfite end-use products for use 

on grapes imported from Chile, an expedited laboratory analysis program (ELAP) conducted 

under an FDA-approved protocol and administered under the Chilean exporters association was 

conducted to monitor all the grapes imported in 1988-1989. For the registration of sulfur dioxide 

end-use products, controlled experiments were conducted to test sulfite residues in/on grapes 

exposed to sulfur dioxide (E. T. Harber, 02/08/1989 and 02/25/1989). In the 2007 RED, the 10 

ppm tolerance for residues of sulfur dioxide in/on grapes was supported. 

For sulfur dioxide end use products, current labels allow a high dosage use with an initial 

application at concentrations of 1% followed by up to 12 (Thompson seedless varieties), 15 

(other seedless varieties) or 20 (seed varieties) subsequent applications at concentrations of 0.5%

in a 7-10 day interval. However, residue data for the high dosage use at weekly intervals 

supports initial application of 0.5% followed by 12 applications of 0.25% (M. J. Bradley, 

D156294, 09/13/1990). Since residues are likely to decline significantly in one week, HED has 

no objection to keeping the current 1% initial application rate assuming at least 1 week between 

that application and marketing of the commodity. However, subsequent applications should be 

restricted to 0.25% as represented by available residue data since these applications more likely 

to affect residue levels of grapes reaching the market. Based on information provided by 

pesticide registrants and their representatives, subsequent applications of 0.25% are standard 

industry practice (Letter to K. Nguyen dated 05/21/2013). The maximum number of 

fumigations recommended by HED for the high dosage use is 12. A modified use pattern

supported by the available residue data may be proposed by the registrant. Alternatively, if the 

current labeled rate is requested by the registrant, additional residue data supporting the labeled 

use must be submitted. 

An analytical enforcement method (see 21 CFR Part 101 Appendix A) is available for 

enforcement of tolerances for sulfites at 10 ppm in food. The method transforms residues of 

sulfite to sulfur dioxide, the latter is converted to sulfuric acid and quantified by titration; 

residues are expressed as sulfur dioxide. The FDA Center for Food Safety and Applied Nutrition 

evaluated 16 samples of grapes from 1999 to 2009. One sample of grapes imported from 

Mexico exceeded the tolerance and sulfur dioxide was declared in the product. 

Currently, the 40 CFR § 180.444 has permanent tolerance for sulfite residues (determined as 

sulfur dioxide) in/on grapes at 10 ppm. In addition, a time-limited tolerance for sulfites in/on 

figs (10 ppm) is included (P. Savoia, D392201, 09/01/2011). HED established interim guidance 

on writing tolerance expressions for enforcement purposes (S. Knizner, 27/May/2009). In order 

to add clarity to the language used to establish the coverage of the tolerance expression and 

measurement of the level of the residue in the Raw Agricultural Commodity (RAC) the text in 

the 40 CFR § 180.444 should read: “(a) General. (1) Tolerances are established for residues of 

sulfur dioxide and sodium metabisulfite (sulfur dioxide generator), including their metabolites 

and degradates, in or on the commodities in the table below. Compliance with the tolerance 

levels specified below is to be determined by measuring only those sulfite residues convertible to 

sulfur dioxide, expressed as sulfur dioxide, in or on the commodity.”
Page 8 of 25

Conclusions: The residue chemistry deficiencies/recommendations below need to be addressed.

For sulfur dioxide end-use products, residue data depicting the label use pattern may be 

required. Alternatively, modified use pattern supported by the available residue 

chemistry data may be proposed. 

Modification of the tolerance expression in the 40 CFR § 180.444 according to the new 

HED guidance.

4.0 DIETARY EXPOSURE

Based on the grape metabolism study, sulfites were identified as the residue of concern. The

FDA requires ingredient labels to list sulfite concentrations in excess of 10 ppm (expressed as 

SO2) in order to protect sulfite sensitive individuals. A tolerance of 10 ppm for grapes and figs 

was supported by the 2007 RED. Assuming the provocative dose established by the FDA (3.7 

mg), residues of sulfites at the tolerance level are not expected to be of concern for the US 

population. 

Sulfites also occur naturally in some foods as a result of fermentation. In addition, other sources 

of sulfites include uses in alcohol regulated by the Alcohol and Tobacco Tax and Trade Bureau, 

and uses as food additives and as components of pharmaceuticals regulated by the FDA. Uses as 

food additives may result in concentrations >100 ppm in dried fruits, juices, molasses, and 

sauerkraut juice, between 50 and 100 ppm in dried potatoes, grape juice, wine vinegar, gravies, 

fruit topping, and maraschino cherries, and between 10 ppm and 50 ppm in pectin, fresh shrimp, 

corn syrup, sauerkraut, pickled foods, corn starch, hominy, frozen potatoes, maple syrup, 

imported jams and jellies, and fresh mushrooms (Lester 1995 as cited in CIR 2003). 

The pesticide uses of the inorganic sulfites may lead to lower sulfites residue levels than those 

resulting from food additive uses. However, the Agency may consider other sources of sulfites 

during registration review. The FDA is undergoing an effort to prepare a dietary risk assessment 

considering several sources of exposure to sulfites in food. In addition, a new point of departure 

may be selected based on human clinical trial data. 

Conclusions: The EPA will work with the FDA to determine residue levels in various foods 

and appropriate methods for assuring safe levels of dietary consumption of sulfite residues.

5.0 TOLERANCE ASSESSMENT AND INTERNATIONAL HARMONIZATION

Where possible, EPA encourages the harmonization of the US Tolerances and Maximum 

Residue Limits (MRLs) in key export markets. A table with the US tolerances, the Canada 

MRLs, Mexico MRLs and Codex MRLs for sulfur dioxide in registered RACs is provided in 

Appendix C- International Residue Limits. There are currently no established Codex, Canadian 

and/or Mexican MRLs for sulfur dioxide in/on grapes; therefore, harmonization is not germane 

to this action. 
Page 9 of 25

6.0 RESIDENTIAL EXPOSURE

There are currently no registered residential uses of sodium metabisulfite or sulfur dioxide. 

There is the potential for bystander exposures which can occur from emissions during treatment 

and aeration of commodities and structures. Structures and other treated spaces can leak during 

treatment and also will off-gas during aeration after application which creates a potential for 

bystander exposure for those nearby such treatments.

 

In the 2007 RED for inorganic sulfites, a Probabilistic Exposure and Risk Model for Fumigants 

(PERFUM) analysis was completed and it was concluded that there was concern for bystander 

exposure during grape fumigations which involve the release of high levels of sulfur dioxide 

during aeration. To address this concern, it was stated that a maximum release concentration 

was established at 30 ppm for warehouse treatments and at 2 ppm for truck/trailer treatments. 

The maximum release concentration for warehouses was greater than the concentration for 

trucks/trailers based on the release of treated air following warehouse fumigation at a greater 

flow rate and a greater height above ground level, thereby reducing the potential for bystander 

exposure. Based on the results of the PERFUM model, these release concentration levels are 

expected to limit bystander exposure potential to sulfur dioxide concentrations at or below 0.25 

ppm, which is the ambient air quality standard set by the California Air Resources Board. Refer 

to Appendix D for recommended label revisions from the 2007 RED. The RED also showed the 

correlation between buffer zone size and release concentration for the sulfur dioxide grape 

fumigation scenario. 

The Agency has specifically focused on assessing acute inhalation exposures resulting from 

fumigation applications because peak air concentrations typically occur at the beginning of 

active aeration. For registration review and as done for other fumigants, these exposures will 

need to be characterized, including the use of computer modeling analyses (e.g., PERFUM) and 

estimation of potential buffer zones required assure bystander and worker safety. Fumigation 

use and emission/aeration information are required to address potential bystander exposure. 

Residential assessments may be needed during registration review if a significant potential for 

risk concern is identified. 

There is the potential for inhalation exposure to sulfur dioxide via ambient air. These exposures 

can be acute as well as longer-term in nature. Ambient air data are typically required for 

fumigants. However, sulfur dioxide in ambient air comes from numerous, non-pesticidal 

sources, and is a criteria air pollutant regulated by EPA’s Office of Air Quality Planning and 

Standards (OAQPS) who has worked extensively on sulfur dioxide1, including setting national 

ambient air quality standards (NAAQS) for sulfur dioxide. Therefore, ambient air monitoring 

data are not required by OPP for its use as a fumigant; rather, OPP defers to OAQPS for 

regulation of ambient air levels. 

Conclusions: As done in other fumigant risk assessments, bystander risk to sulfur dioxide 

emissions from treated commodities and structures may need to be evaluated depending on 

 

1

http://www.epa.gov/airquality/sulfurdioxide/
Page 10 of 25

sulfur dioxide emission information and the label prescribed use conditions. Fumigation use 

information is also required under Registration Review for assessment of potential buffers for 

aeration of enclosed spaces. A bystander exposure assessment may be required for Registration 

Review. 

7.0 AGGREGATE EXPOSURE AND RISK ASSESSMENT

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. For sulfites, 

allergic reactions in sensitive individuals are the reason for required limitations in sulfite 

ingestion rather than any systemic toxicity. In the absence of significant systemic toxicity, a 

quantitative dietary (food and drinking water) risk assessment was not performed for the RED. 

Since similar effects would not be expected to occur through dermal or inhalation exposure, and 

significant incidental oral exposure is not expected, the aggregate assessment includes only the 

dietary exposure scenario, for which quantification of risks is not appropriate. For sulfur 

dioxide, exposure is primarily through inhalation; significant oral and dermal exposures are not 

expected. Additionally, since the inhalation endpoint for sulfur dioxide is different from that for 

the ingested sulfite residues, aggregation across routes is not appropriate. Based on this 

bystander exposure to sulfur dioxide would not be aggregated with other routes of exposure. 

HED will reevaluate the need for quantification of aggregate dietary exposures based on the 

results of the ongoing FDA hazard and risk assessment.

8.0 OCCUPATIONAL EXPOSURE 

Sodium metabisulfite is registered for post-harvest fumigation of grapes held in cold storage. 

Sodium metabisulfite is a solid formulation which produces sulfur dioxide gas when it absorbs 

water or moisture after being exposed to the atmosphere.

Sulfur dioxide is registered for grape fumigation in trailers, railcars, vehicles and warehouses. 

Sulfur dioxide is formulated as a liquid under pressure which forms a gas upon release for 

fumigation. The gas is dispensed from a steel cylinder through a hose into the interior of an 

enclosed, sealed structure. Occupational exposure limits (can be found in Appendix A. After 

treatment, the structure remains closed for a period of time after which aeration begins. Labels 

require use of a respirator when sulfur dioxide concentrations exceed 2 parts per million (ppm). 

The label prohibits people not wearing a NIOSH-approved self contained breathing apparatus 

(SCBA) from entering the treated areas until air levels of sulfur dioxide have declined to 2 parts 

per million (ppm) or less. The personal protective equipment (PPE) requirements and labeling 

language ensure that workers are not exposed to sulfur dioxide levels of concern.

Sulfur dioxide may also be used to treat barrels and corks used in wine production and for 

fumigation of figs. In both cases, cylinderized SO2 is used.

Handlers
Page 11 of 25

There is potential for occupational applicator inhalation exposure to sulfur dioxide during 

fumigation. Applicator exposures are likely to be of short- and intermediate-term exposure 

duration. No worker exposure data were submitted to the Agency regarding the fumigation of 

structures, barrels or corks used in wine production and/or food commodities. As such, data 

regarding potential worker exposure associated with structure and commodity fumigation will be 

required. Handlers are required to wear protective clothing, gloves and boots. Respiratory 

protection is also required when checking connections or making gas applications. 

Post-application Workers

There is potential for occupational post-application inhalation exposure to sulfur dioxide while 

handling treated grapes or wine making supplies. These exposures can possibly occur because 

SO2 may continue to volatilize from treated commodities or the metabisulfite pads might contain 

residual quantities of SO2. This exposure may be short- and intermediate-term in duration for 

workers. Exposure data for cold-storage workers and perhaps those further down the distribution 

chain (e.g., supermarket workers who unpack grape pallets) are required because of these 

possible exposures. Emission-rate data for potential exposures due to off-gassing from treated 

facilities/commodities for workers conducting post-application activities need to be submitted to 

the Agency.

There is potential for occupational post-application inhalation exposure to sulfur dioxide in/on 

fumigated commodities contained in warehouses, cold storage rooms, trucks, vans, boxcars, and 

other vehicles. Air/ worker monitoring data are required under Registration Review. As part of 

registration review, tasks for workers near fumigation facilities/operations need to be defined to 

properly assess post-application activities (i.e. aerators, fork-lift operators, etc.). Potential 

exposures due to off-gassing will be assessed for workers conducting post-application activities 

near treatment operations.

Conclusions: A new occupational handler risk reassessment may be required during registration 

review based on exposure and/or toxicity data. A new occupational post-application assessment 

may be required under registration review based on exposure and/or toxicity data.

9.0 PUBLIC HEALTH AND PESTICIDE EPIDEMIOLOGY DATA

Adapted from: E. Evans and S. Recore, D411761, 05/15/2013

OPP’s Incident Data System (IDS) includes reports of alleged human health incidents from 

various sources, including mandatory Federal Insecticide, Fungicide and Rodenticide Act 

(FIFRA) Section 6(a)(2) reports from registrants, other federal and state health and 

environmental agencies, and individual consumers. IDS records incidents resulting in higher 

severity outcomes in more detail, in a module called the Main IDS module. Main IDS incidents 

involving only one pesticide are considered to provide more certain information about the 

potential effects of exposure from the pesticide. The less severe human incidents (minor, 

unknown, or no effects outcomes) are reported by registrants as counts called aggregate 

summaries and are recorded in a separate module called Aggregate IDS. 
Page 12 of 25

For the Main IDS from January 1, 2008 to February 19, 2013 there were no incidents reported in 

the database involving sulfur dioxide or sodium metabisulfite. In the Aggregate IDS, from 

January 1, 2008 to February 19, 2013, there were no reported incidents involving sulfur dioxide 

or sodium metabisulfite. 

The SENSOR-Pesticides database covers 11 states from 1998-2009, although reporting varies 

from state to state. A query of SENSOR-Pesticides from 1998-2009 identifies 30 cases, 

stemming from 27 events, involving sulfur dioxide. Twenty five cases involved a single active 

ingredient and 6 cases involved multiple active ingredients. Of the 25 single ai cases, all were 

work-related. One case was high in severity, 10 were moderate in severity and 14 were low in 

severity. Twenty four of the cases occurred in California. Respiratory effects were the most 

commonly reported symptom. Fourteen of the 25 cases were conducting routine work activity 

not involved with pesticide application at the time they were exposed; three cases were applying 

the pesticide, five cases were mixing or loading the pesticide, and the remaining three were 

conducting unknown work activities. Limited or missing case detail from the California case 

reports makes it difficult to further pinpoint a pattern from these incidents. The 2007 RED made 

sulfur dioxide product label changes and clarified PPE language meant to better protect workers. 

Because many of the SENSOR-Pesticides cases from California did not include a case 

description; a query of sulfur dioxide cases was conducted in California’s Pesticide Illness 

Surveillance System (PISP). The PISP query finds that only 3 sulfur dioxide cases have been 

reported since 2007; which supports the conclusion that sulfur dioxide does not present a risk of 

concern at this time. 

For sodium metabisulfite (PC code 111409) and sodium bisulfite (PC code 078201; active 

ingredient previously identified), and a query of SENSOR-Pesticides 1998-2009 identifies a total 

of 4 cases, stemming from 2 events. There were three fatalities and one low severity case 

reported. This multiple fatality event was considered by EPA in the 2007 Inorganic Sulfites RED 

and the deaths were determined not to be resultant of a pesticidal use.2 

Conclusions: No sulfur dioxide cases have been reported into IDS. SENSOR-Pesticides, 

however, continues to see a low frequency of occupational sulfur dioxide cases reported from 

California related to grape fumigation. EPA will continue to monitor these incidents to see if 

sulfur dioxide incidents are declining as a result of the mitigation requirements. Based on the 

low frequency and severity of reported cases there does not appear to be a risk of concern at this 

time. One event involving sodium bisulfite reported to SENSOR-Pesticides in 1999 resulted in 

three fatalities. EPA was aware of this event at the time of the 2007 RED and determined the 

fatalities were not related to pesticide use of the chemical. Therefore pesticide incidents are low 

in frequency and there does not appear to be a concern for sodium bisulfate at this time.

10.0 ENVIRONMENTAL JUSTICE

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

 

2

Ibid.
Page 13 of 25

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the USDA under the Continuing 

Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to 

assess dietary exposure to smaller, specialized subgroups, and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary 

exposures based on home use of pesticide products and associated risks for adult applicators and 

for toddlers, youths, and adults entering or playing on treated areas post-application are 

evaluated. Further considerations are currently in development as OPP has committed resources 

and expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.

11.0 CUMULATIVE RISK ASSESSMENT

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to sulfur dioxide/sodium metabisulfite and any other substances and sulfur dioxide/sodium 

metabisulfite does not appear to produce a toxic metabolite produced by other substances. For 

the purposes of this tolerance action, therefore, EPA has not assumed that sulfur dioxide/sodium 

metabisulfite has a common mechanism of toxicity with other substances. For information 

regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity 

and to evaluate the cumulative effects of such chemicals, see the policy statements released by 

EPA’s Office of Pesticide Programs concerning common mechanism determinations and 

procedures for cumulating effects from substances found to have a common mechanism on 

EPA’s website at http://www.epa.gov/pesticides/cumulative/.

12.0 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 sulfur dioxide/sodium 

metabisulfite, EPA reviewed these data and selected the most sensitive endpoints for relevant 
Page 14 of 25

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

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

the Endocrine Disruptor Screening Program (EDSP). 

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 the E, 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, 20133and 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.4

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

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

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

13.0 HUMAN STUDIES

The Agency is aware of 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 the inorganic sulfites.

If after considering any of these studies and/or those 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.

 

3

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

chemicals.

4

http://www.epa.gov/endo/
Page 15 of 25

14.0 DATA REQUIREMENTS

Occupational/Residential Exposure5

875.1400 Inhalation Exposure Study for Applicators. These studies are required to assess 

exposures for applicators involved in fumigating commodities/materials and/or structural 

facilities. 

875.1700 Product Use Information. This information is required to assess product use 

parameters by major use region, frequency, and application equipment. 

875.2500 Post-Application Inhalation Exposure Study. This study is required to assess postapplication exposures for workers near fumigation facilities/operations or who work directly 

with previously treated commodities/materials.

Special Studies - Monitoring data on fumigated commodities. Special studies are required to 

evaluate emission rates for sulfur dioxide from treated commodities/materials and the potential 

for occupational exposure due to those emissions in the channels of trade after fumigation 

activities are complete.

Residue Chemistry

860.1500 Crop Field Trials. This study is required to support the high dosage use of sulfur 

dioxide end use products as stated in the label.

15.0 REFERENCES

 

EPA 2002. 2002 Edition of the Drinking Water Standards and Health Advisories. EPA

822/R/02/038. Washington, DC: Office of Water, EPA.

National Academy of Sciences, Institute of Medicine, Food and Nutrition Board, 2004, Chapter 

7: Dietary Reference Intakes for Water, Potassium, Sodium, Chloride and Sulfate.

http://www.nal.usda.gov/fnic/DRI/DRI_Water/water_full_report.pdf

Sulfate in Drinking-water; Background document for development of WHO Guidelines for 

Drinking-water Quality; http://www.who.int/water_sanitation_health/dwq/chemicals/sulfate.pdf

Sulfur Dioxide and Inorganic Sulfites: Summary of Hazard and Science Policy Council 

(HASPOC) Meeting of May 9, 2013: Recommendation on Multiple Toxicology Studies; Julie 

Van Alstine, MPH; 05/21/2013.

 

5 Ambient air data are typically required for fumigants. However, sulfur dioxide is a criteria pollutant and EPA has 

set National Ambient Air Quality Standards (NAAQS) for sulfur dioxide, therefore, additional data are not required 

for use as a fumigant. 
Page 16 of 25

Inorganic Sulfites (Sulfur Dioxide and Sodium Bisulfite): Review of Human Incidents; Elizabeth 

Evans and Shanna Recore; D411761; 05/15/2013.

Sulfur Dioxide. Section 18 Emergency Exception for the Post-Harvest Use of Sulfur Dioxide on 

Fresh Figs to Control Botrytis Cinerea in California; D392201; 09/01/2011.
Page 17 of 25

Appendix A: Toxicology Database and Data Requirements

A1. Toxicology Data Requirements

The requirements (40 CFR 158.500) for food use for sulfur dioxide are presented below. Use of the new guideline 

numbers does not imply that the new (1998) guideline protocols were used.

Test Technical

Required (CFR) Satisfied a

870.1100 Acute Oral Toxicity ................................................................................

870.1200 Acute Dermal Toxicity............................................................................

870.1300 Acute Inhalation Toxicity .......................................................................

870.2400 Primary Eye Irritation .............................................................................

870.2500 Primary Dermal Irritation........................................................................

870.2600 Dermal Sensitization...............................................................................

yes

yes

yes

yes

yes

yes

no

no

no

no

no

no

870.3100 Oral Subchronic (rodent) ........................................................................

870.3150 Oral Subchronic (nonrodent)...................................................................

870.3200 21-Day Dermal .......................................................................................

870.3250 90-Day Dermal .......................................................................................

870.3465 90-Day Inhalation ...................................................................................

yes

yes

yes

no, cr

yes, cr

no

b

no b

no b

-

No

a

870.3700a Developmental Toxicity (rodent) ............................................................

870.3700b Developmental Toxicity (nonrodent) ......................................................

870.3800 Reproduction...........................................................................................

yes

yes

yes

No

a

No

a

No

a

870.4100a Chronic Toxicity (rodent)........................................................................

870.4100b Chronic Toxicity (nonrodent) .................................................................

870.4200a Oncogenicity (rat) ...................................................................................

870.4200b Oncogenicity (mouse).............................................................................

870.4300 Chronic/Oncogenicity.............................................................................

yes

yes

yes

yes

no

No

a

No

a

No

a

no

=

870.5100 Mutagenicity—Gene Mutation - bacterial...............................................

870.5300 Mutagenicity—Gene Mutation – mammalian.........................................

870.5375 Mutagenicity—In vitro Chromosomal Aberrations.................................

870.5385 Mutagenicity—In vivo Chromosomal Aberrations....

870.5395 Mutagenicity—Erythrocyte Micronucleus Test ......................................

yes

yes

yes

yes

yes

No

a

No

a

No

a

No

a

No

a

870.6100a Acute Delayed Neurotox. (hen)...............................................................

870.6100b 90-Day Neurotoxicity (hen)....................................................................

870.6200a Acute Neurotox. Screening Battery.........................................................

870.6200b 90-Day Neurotox. Screening Battery ......................................................

870.6300 Develop. Neurotox..................................................................................

no, cr

no, cr

yes

yes

no, cr

-

-

No

a

No

a

-

870.7485 General Metabolism................................................................................

870.7600 Dermal Penetration .................................................................................

870.7800 Immunotoxicity.......................................................................................

yes

no, cr

yes

No

a

-

No

a

a The requirements for these studies may be met by performing the guideline study. Alternatively, the HASPOC is aware that numerous 

literature studies exist for sulfur dioxide, and the HASPOC further believes that many of these literature studies may be sufficient to provide 

information which could be used in lieu of guideline studies. Also, it is expected that HED will be able to rely on the ongoing FDA review 

of human clinical data for hazard characterization of sulfites, and guideline toxicity studies will not be required. 

b The requirements for these studies have been waived by HASPOC.

A2. Toxicology Database

Table A2.1. Sulfur Dioxide Air Concentrations used for Regulatory/Guideline 

Purposes1

Exposure Limit Agency/Group Regulatory/Guideline Level 

(ppm)

1-hour WHO 0.13

California Air Resources Board 0.25

AIHA (ERPG-1) 0.3

State of Washington 0.25
Page 18 of 25

State of North Dakota 0.27

State of Montana 0.5

3-hour US EPA 0.5

State of Florida 0.5

State of Maine 0.4

State of New Mexico 0.5

State of New York 0.25

State of Oregon 0.02

1 Adapted from the 2007 RED.

A2.1. Exposure Limits and Health Effects (Adapted from OSHA)1

Exposure Limit Limit Values HE Codes Health Factors and Target 

Organs

OSHA Permissible Exposure Limit 

(PEL) - General Industry

See 29 CFR 1910.1000 Table Z-1 

5 ppm 

(13 mg/m3) TWA

HE14 Upper respiratory irritation, 

nosebleeds

OSHA PEL - Construction Industry

See 29 CFR 1926.55 Appendix A

5 ppm 

(13 mg/m3) TWA

HE14 Upper respiratory irritation, 

nosebleeds

OSHA PEL - Shipyard Employment

See 29 CFR 1915.1000 Table ZShipyards

5 ppm 

(13 mg/m3) TWA

HE14 Upper respiratory irritation, 

nosebleeds

National Institute for Occupational 

Safety and Health (NIOSH) 

Recommended Exposure Limit 

(REL) 

2 ppm 

(5 mg/m3) TWA

5 ppm 

(13 mg/m3) STEL

HE4 Blindness

HE9 Bronchoconstriction

HE11 Breathing difficulties

HE14 Eye and respiratory irritation, 

eye and skin burning

American Conference of 

Governmental Industrial Hygienists 

(ACGIH) Threshold Limit Value 

(TLV) (2009)

0.25 ppm 

(0.65 mg/m3) 

STEL

A4

HE9 Bronchoconstriction, 

exacerbation of asthma

HE10 Decreased lung function, 

chronic respiratory symptoms

HE11 Lower respiratory irritation 

and symptoms

HE14 Upper respiratory irritation

CAL/OSHA PELs 2 ppm 

(5 mg/m3) TWA 

5 ppm 

(10 mg/m3) STEL

1

http://www.osha.gov/dts/chemicalsampling/data/CH_268500.html
Page 19 of 25

A.2.2. Regulatory Values for Sulfur Dioxide and Inorganic Sulfites a

EPA Sulfite residues on grapes, postharvest; used as fungicide and preservative: 10 ppm

EPA Pesticide worker protection: When concentrations exceed 2.0 ppm in the fumigation area, 

NIOSH/MSHA-approved respirators must be worn

EPA Bystander inhalation: 0.25 ppm

EPA National Primary Ambient Air Quality Standards (NAAQS). Sulfur oxides: long term 

concentration averaging 0.03 ppm over 1 year (annual arithmetic mean) REVOKED; short term 

concentration averaging 0.14 ppm over 24 hrs (not to be exceeded more than once a year)

REVOKED; 1-hour exposure limit: 0.075 ppm

California Acceptable ambient air concentration: 0.25 ppm for 1 hr; 0.04 ppm for 24 hr

OSHA PEL Short-term exposure limit: 5 ppm; time-weighted avg: 2 ppm

WHO 10 min exposure limit: 0.2 ppm; 1-hr exposure limit: 0.13 ppm; 24-hour exposure limit: 0.04-0.06

ppm; annual arithmetic mean: 0.015-0.023 ppm

FDA Generally recognized as safe (GRAS) when used in accordance with good manufacturing or 

feeding practice, except that it is not used in meats or in food recognized as source of vitamin B1

CERCLA Extremely hazardous substance; reporting requirements when stored in excess of 500 lbs.

ACGIH 15-min short term exposure limit (STEL): 0.25 ppm; A4; Not classifiable as a human carcinogen

NIOSH Recommended Exposure Limit: 10-hr time-weighted avg: 2 ppm

NIOSH Recommended Exposure Limit: 15-min short-term exposure limit: 5 ppm

NIOSH Immediately dangerous to life or health: 100 ppm

IARC Carcinogen classification Group 3 (not classifiable as to its carcinogenicity in humans)

American 

Industrial 

Hygiene 

Association

ERPG-1, the maximum airborne concentration below which it is believed that nearly all persons 

could be exposed for up to 1 hour without experiencing other than mild transient adverse health 

effects or perceiving a clearly defined, objectionable odor: 0.3 ppm

a From the National Library of Medicine’s Hazardous Substance Data Bank, last revised on April 30, 2010, 

ATSDR (December 1998), Reregistration Eligibility Decision – Inorganic Sulfites (May 2007), 

www.OSHA.gov, and www.arb.ca.gov/research/aaqs/aaqs2.pdf. 
Page 20 of 25

Appendix B: Chemistry

1.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION

1.1 Identification of Active Ingredient

Table 1.1 Test Compound Nomenclature

Chemical Structure

Empirical Formula SO2 Na2S2O5

Common Name / 

IUPAC name Sulfur Dioxide Sodium Metabisulfite

CAS Registry Number 7446-09-05 7681-57-4

1.2 Physical and Chemical Properties

Table 1.2 Physico-Chemical Properties

Property Sulfur Dioxide References Sodium Metabisulfite References

Molecular Weight 64.06

ATSDR, 

1998a

NIOSH, 

1994

190.19

HSDB, 

2005

Color/Form Colorless gas White crystals or powder

Odor Strong suffocating 

odor

Slight odor of sulfur 

dioxide

Melting point -72.7 °C 150 °C

Boiling point

-10 °C Decomposes OECD, 

2001

Density 2.927 g/L 1.4 g/cm3

HSDB, 

2005 Solubility in Water 22.8 g/100mL (0 °C) 54 g/L (20 °C)

1 Adapted from the RED (May 2007) for the Inorganic Sulfites.
Page 21 of 25

Appendix C: International Residue Limits 

Sulfur Dioxide (PC Code 077601)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex

40 CFR 180.444:

A tolerance is established as follows for 

sulfite residues of the fungicide sulfur 

dioxide (determined as (SO2)) 

None None

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex

Grape, postharvest 10

Completed: M. Negussie; 03/13/2013

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

(b) Section 18 emergency exemptions. Time-limited tolerances specified in the following table 

are established for residues of sulfur dioxide, including its metabolites and degradates in or on 

the specified agricultural commodities, resulting from use of the pesticide pursuant to FFIFRA 

section 18 emergency exemptions. Compliance with the tolerance levels specified below is to be 

determined by measuring only sulfur dioxide (SO2 ). The tolerances expire on the date specified 

in the table.

Commodity

Parts per

million Expiration/revocation date

Fig 10 12/31/14
Page 22 of 25

Appendix D: Label Revisions Recommended in the 2007 RED

Table 1.: Label Statements for Sulfur Dioxide End-Use Products

“When treating grapes for Botrytis cinerea (bunch rot/gray mold) or black widow spider in

a warehouse fumigation chamber, do not release treated air into the atmosphere containing

concentrations of sulfur dioxide in excess of 30 ppm (as determined by a Sensidyne or

Kitagawa syringe sampler, or a Draeger handpump).”

“When treating grapes in a truck, trailer or other transport vehicle, do not release treated air

into the atmosphere containing concentrations of sulfur dioxide in excess of 2 ppm (as

determined by a Sensidyne or Kitagawa syringe sampler, or a Draeger handpump).”

“Sulfur dioxide concentration in transport vehicles must be below 2 ppm before moving

over public roads or highways.”

“Before moving or using this product, handlers must be trained how to appropriately use

respirators which conform to OSHA requirements (described in 29 CFR Part 1910.124) and

how to appropriately handle and use sulfur dioxide.”

“When making gas applications or checking connections wear a NIOSH/MSHA approved

full face respirator with an organic-vapor removing cartridge, in addition to sulfur dioxide impervious 

gloves, boots and coveralls over long-sleeved shirt and long pants.”

“If a sulfur dioxide concentration of 2 ppm is exceeded at any time, all persons working in

the fumigation area must wear a NIOSH/MSHA approved full face respirator with an

organic-vapor removing cartridge. If sulfur dioxide concentrations of 10 ppm are

exceeded, or when concentrations are unknown, an approved self-contained breathing mask

(SCBA) or combination air supplied SCBA respirator must be used by all persons working

in the fumigation area.”

“Do not perform sulfur dioxide aerations concurrently from multiple chambers.”

Table 2. Label Statements for Sodium Metabisulfite End-Use Products (pad labeling)

“This pad contains sodium metabisulfite which may trigger an asthmatic response in sulfite

sensitive individuals.”

“This pad must be removed and disposed of prior to displaying grapes for sale. Do not

allow consumers access to pads.”

“If pad is torn: Carefully dispose of pad, pad contents, and grapes which have contacted

pad contents.”

“For Disposal: Place pad in a plastic bag, seal bag and place in an outdoor trash receptacle

(dumpster).”
Page 23 of 25

Appendix F: Data Call-In

Guideline Number: 875.1400 

Study Title: Inhalation Exposure Study for Applicators (for sulfur dioxide fumigation in enclosed 

spaces).

Rationale for Requiring the Data 

The inhalation exposure route is very important for exposure scenarios such as fumigation activities 

where gases will be generated. However, very limited worker exposure monitoring data are available for 

workers involved in the fumigation of commodities, other materials, and/or structural facilities. These 

data do not address the breadth of possible activities associated with sulfur dioxide uses that are of 

potential risk concern. Traditional sources of worker exposure information (e.g., Pesticide Handlers 

Exposure Database or PHED) have not been used to supplement the existing data and do not apply 

because of the highly volatile nature of sulfur dioxide. 

To protect workers from inhalation exposure to pesticides, the Agency requires inhalation exposure 

monitoring data. These data will ensure that the Agency has the most accurate information possible to 

assess exposures for those involved in the fumigation process. In addition, these data will be used during 

registration review to evaluate the potential for sulfur dioxide occupational exposure to fumigators who 

treat structural facilities, commodities, and other materials, and will inform the Agency as to how to 

manage any risks which may be identified based on these data which will reflect the current use practices 

for sulfur dioxide. 

Practical Utility of the Data 

How will the data be used? 

The inhalation exposure data will be used to assess occupational risks for workers involved in fumigation 

activities during treatment of commodities, materials and/or structural facilities. 

How could the data impact the Agency’s future decision-making? 

The inhalation exposure data will be used to determine the accuracy of the inhalation risks to occupational 

applicators during fumigation activities based on modern fumigation practices. If future risk assessments 

are performed without these data, the Agency will have to factor a significant degree of uncertainty into 

its regulatory decision-making process and that the current mitigation measures (i.e., personal protective 

equipment) may not provide adequate protection for workers applying sulfur dioxide in structural 

facilities and/or during the treatment of commodities and other materials. 

The lack of these data will limit the flexibility of the Agency and registrants with respect to the ability to 

evaluate risks associated with the modern use practices associated with sulfur dioxide. It will also allow 

the Agency to refine its previous risk assessment and could be used to defend challenges to the sulfur 

dioxide decision and to consider additional sources of exposure to those involved in the fumigation 

process. 

Guideline Number: 875.1700 

Study Title: Product Usage Information 

Rationale for Requiring the Data 

The Agency’s understanding of sulfur dioxide products and usage is limited to the directions found on 

pesticide labels and estimates of the amounts used to treat certain commodities or structures. The Agency, 

believes that the current understanding of the sulfur dioxide usage pattern is not sufficient to assess the 

full range of potential exposure associated with its use because how it is applied, how much is applied, 

and associated fumigation practices (e.g., aeration methods) can impact exposures and these data are not 

available in a systematic manner. 

Additional data are necessary to understand sulfur dioxide usage in terms of both commodity and facility 
Page 24 of 25

fumigations and the potential exposures as a result of these uses. These data will ensure that the Agency 

has the most accurate information possible to assess product usage parameters by major use region, 

frequency, season, maximum and typical rates, and application equipment/procedures. In addition, these 

data will be used during registration review to evaluate the potential exposure for workers and the general 

public. 

Practical Utility of the Data 

How will the data be used? 

This information will be used to confirm the end-use products, use patterns, usage assumptions and 

parameters to determine exposures to sulfur dioxide for humans or provide the basis for possible 

refinements to the process based on a more thorough understanding of modern fumigation practices. 

How could the data change the Agency’s decision? 

Additional precautions and/or restrictions may be necessary to protect workers and the general public 

from exposures to sulfur dioxide as a consequence of commodity/material fumigations and/or fumigation 

of structural facilities. These data will allow the Agency to refine its previous risk assessment and could 

be used to defend challenges to the sulfur dioxide decision. 

Guideline Number: 875.2500 

Study Title: Post-Application Inhalation Exposure Study (for sulfur dioxide fumigation in 

enclosed spaces).

Rationale for Requiring the Data 

Postapplication inhalation exposure to sulfur dioxide is predicted to occur as a result of the registered uses 

of sulfur dioxide, including commodity/material fumigation and/or structural fumigations. The existing 

data for exposure to sulfur dioxide are limited in terms of the variety of post-application activities and the 

potential exposures due to off-gassing from treated structural facilities and commodities. 

The original data requirements were not broad enough to assess risks to occupational workers near 

fumigated facilities treated with sulfur dioxide or who have to work directly with sulfur dioxide treated 

commodities/materials that could result in post-application exposures which may be a concern. These data 

will ensure that the Agency has the most accurate information possible to assess post-application 

exposures for workers near fumigation structural facilities/operations or who work with treated 

commodities/materials. In addition, these data will be used in registration review to determine if the 

potential for postapplication occupational exposure for workers near fumigation facilities/operations is 

below the Agency’s level of concern or establish further risk management needs that would apply to the 

use of sulfur dioxide. 

Practical Utility of the Data 

How will the data be used? 

These data will be used to determine inhalation exposure to sulfur dioxide for workers conducting a 

variety of post-application activities near fumigated facilities/commodities or who work directly with 

treated commodities/materials. 

How could the data impact the Agency’s future decision-making? 

The post-application inhalation exposure study will provide data to support and fully characterize and 

quantify the exposure and risks of workers exposed to this pesticide. Due to the lack of data, the Agency 

has used assumptions in developing the risk assessment. These data will allow the Agency to refine its 

previous risk assessment and could be used to defend challenges to the sulfur dioxide decision. 
Page 25 of 25

Special Study: Monitoring data on fumigated commodities with Sulfur dioxide (from sodium 

metabisulfite pads). 

Rationale for Requiring the Data 

The potential postapplication exposures associated with commodity fumigation were not quantitatively 

assessed when these uses were established. The Agency did not have monitoring data to directly measure 

emissions of sulfur dioxide from fumigated commodities/materials. 

These data will ensure that the Agency has the most accurate information possible on exposure to 

evaluate emission rates from treated commodities. Postapplication risks estimates will be calculated for 

workers exposed to sulfur dioxide and will be used to determine if the potential for occupational exposure 

due to those emissions (i.e., for postapplication workers who must handle or receive treated commodities) 

is below the Agency’s level of concern. 

Practical Utility of the Data 

How will the data be used? 

These data will be used to determine if the exposure to sulfur dioxide from handling treated 

commodities/materials is below the Agency’s level of concern. In addition, these data will be used to 

inform emissions factors and buffer zone estimates during the treatment and aeration phases of the 

fumigations for sulfur dioxide commodity uses. 

How could the data impact the Agency’s future decision-making? 

These monitoring data are needed to fully characterize emissions from fumigated commodities. These 

data will allow the Agency to refine its previous risk assessment in terms of model parameterization (i.e., 

buffer zones, emissions and other factors). In addition, more precise information appropriate for 

parameterization of the exposure models could be used to refine the previous risk assessment and to 

defend challenges to the sulfur dioxide decision.