UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: May 15,2013 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Inorganic Sulfites (Sulfur Dioxide and Sodium Bisulfite): Review of Human 

Incidents 

PC Code: 077601, 078201, 111 409 

Decision No.: 4775~1 

DP Barcode: 0411 761 

Registration No.: NA 

Regulatory Action: NA 

Case No.: NA 

Petition No.: NA 

Risk Assessment Type: NA 

TXRNo.: NA 

MRIDNo.:NA 

CAS No.: 744609-5, 7631-90-5 

40CFR: NA 

FROM: Elizabeth Evans, Environmental Protection Specialist rrr · ""~ To

Health 

xicology 

Effects 

and 

Division 

Epidemiology 

(7509P) 

Branch q/v ~ 

and 

Shanna Recore, Industrial Hygienist 

Toxicology and Epidemiology Branch 

Health Effects Division (7509P) 

THROUGH: David J. Miller, Acting Branch Chief 

Toxicology and Epidemiology Branch 

Health Effects Division (7509P) 

TO: ldeliz Negron-Encarnacion, Risk Assessor 

Risk Assessment Branch VII 

Health Effects Division (7509P) 

and 

K. Nguyen, Chemical Review Manager 

Risk Management & Implementation Branch VII 

Pesticide Reevaluation Division (7508P) 

and 

C. Cyran, Chemical Review Manager 

Risk Management & Implementation Branch VII 

Pesticide Reevaluation Division (7508P) 

Page 1 of7 
Summary and Conclusions 

Based on a relatively low frequency of incident reports across databases (IDS, SENSOR, and 

CDPR/PISP) for inorganic sulfites there does not seem to be a risk of concern at this time. The 

Agency will continue to monitor the incident information and if a concern is triggered, additional 

analysis will be included in the risk assessment. 

The Agricultural Health Study (AHS) is also a potential source of information associated with 

human health effects associated with certain pesticides. Sulfur dioxide and sodium bisulfite are 

not included in the AHS, and therefore this study does not provide information for this report. 

Detailed Review 

I. ACTION REQUESTED 

This review is intended to fulfill our requirement to docket summaries of incident data that were 

reported to the Agency, as well as to ensure human incident data and the Agricultural Health 

Study (AHS) are part of the problem formulation phase of registration review. Reports of 

adverse health effects allegedly due to a specific pesticide exposure (i.e., an "incident") are 

largely self-reported and therefore, generally speaking, neither exposure to a pesticide or 

reported symptom (or the connection between the two) is validated or otherwise confirmed. 

Typically, causation cannot be determined based on incident data. Howev~r, incident 

information can be an important source of feedback to the Agency: incidents of severe outcome, 

or a suggested pattern or trend among less severe incidents, can signal the Agency to further 

investigate a particular chemical or product. Observational epidemiology studies relate the risk 

of disease, e.g., cancer, and exposure to an agent such as a pesticide product in the general 

population or specific sub-groups like pesticide applicators. 

II. BACKGROUND 

The inorganic sulfites reregistration case includes the chemicals sulfur dioxide (CAS No. 7446-

09-5) and sodium metabisulfite (CAS No. 7681-57-4). As active ingredients, these chemicals 

are fungicides typically used to treat for Botrytis cinerea, the fungus which causes bunch rot, or 

gray mold disease on grapes. The sulfur dioxide products are formulated as a compressed liquid 

that converts to a gas upon release. These products are used in cold-storage warehouses, trucks, 

vans and train cars for post-harvest grape fumigation. The sodium metabisulfite products are 

composed of the anhydrous, solid active ingredient contained in semi-sealed pads which are 

added to containers holding grapes prior to shipping. The pads absorb moisture generated by 

grapes, and release low levels of sulfur dioxide in the range of 1-5 ppm. End-use inorganic 

sulfite products contain sulfur dioxide at 99.9 to 100%, and sodium metabisulfite at 37.5 to 

98.5%. The Agency currently has six of the ten sodium metabisulfite products designated as 

containing sodium bisulfite (078201) as the active ingredient. As ofthe publication of the RED, 

EPA planned to transfer these registrations to the sodium metabisulfite designation ( 111409). 1 

1 Inorganic Sulfites RED: http://www.epa.gov/oppOOOO 1/chem search/reg actions/reregistration/red G-50 1-Mav07.pdf 

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For this evaluation, the OPP Incident Data System (IDS) and the Centers for Disease Control and 

Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event 

Notification System for Occupational Risk (SENSOR)-Pesticides databases were consulted for 

pesticide incident data for inorganic sulfites (PC Codes 077601, 078201, 111409). Additionally, 

the California Department of Pesticide Regulation (CDPR) Pesticide Illness Surveillance 

Program (PISP) was queried for this scoping document in order to supplement the SENSORPesticide data for sulfur dioxide. Generally the Tier I incident scoping documents do not include 

a query ofPISP. However several SENSOR cases, all from California, did not include a 

descriptive narrative making it difficult to identify commonalities among cases. Therefore, PISP 

was consulted in this instance to support conclusions made in this document regarding the 

relatively low frequency of reported sodium bisulfite cases. The purpose of the database search 

is to identify potential patterns in the frequency and severity of the health effects attributed to 

Inorganic sulfites exposure. 

In addition, findings from the AHS were reviewed. The Agricultural Health Study (AHS) is a 

high quality, prospective epidemiology study evaluating the link between pesticide use and 

various health outcomes including cancer. Neither sodium bisulfite nor inorganic sulfites are 

included in the AHS. 

III. RESULTS/DISCUSSION 

a. IDS (Incident Data System) 

OPP's 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. Since 1992, OPP has compiled these reports in IDS. IDS contains reports from 

across the U.S. and most incidents have all relevant product information recorded. Reports 

submitted to the IDS represent anecdotal reports or allegations only, unless otherwise stated in 

the report. 

IDS records incidents in one of two modules: Main IDS and Aggregate IDS: 

o Main IDS contains incidents resulting in higher severity outcomes and provides 

more detail with regard to case specifics. This system stores incident data for 

death, major and moderate incidents, and it includes information about the 

location, date and nature of the incident. Main IDS incidents involving only one 

active ingredient (as opposed to pesticide products with multiple active 

ingredients) are considered to provide more certain information about the 

potential effects of exposure from the pesticide. 

Page 3 of7 
o Aggregate IDS contains incidents resulting in less severe human incidents (minor, 

unknown, or no effects outcomes). These are reported by registrants only as 

counts in what are aggregate summaries. 

Inorganic Sulfites (sulfur dioxide): 

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

in the database involving sulfur dioxide. 

In Aggregate IDS, from January 1, 2008 to February 19,2013, there were no reported incidents 

involving sulfur dioxide. 

Sodium Bisulfite: 

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

in the database involving sodium bisulfite. 

In Aggregate IDS, from January 1, 2008 to February 19,2013, there were no reported incidents 

involving sodium bisulfite. 

b. SENSOR-Pesticides 

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

from state to state. Cases of pesticide-related illnesses are ascertained from a variety of sources, 

including: reports from local Poison Control Centers, state Department of Labor workers' 

compensation claims when reported by physicians, reports from State Departments of 

Agriculture, and physician reports to state Departments of Health. Although both occupational 

and non-occupational incidents are included in the database, SENSOR-Pesticides focuses on 

occupational pesticide incidents, and is of particular value in providing that information. The 

state coordinator at each of the 11 respective state Departments of Health conducts case followup activities such as obtaining medical records to verify symptoms and severity. Using 

standardized protocol and case definitions derived from poison center reporting, the state 

SENSOR-Pesticide coordinator enters the incident information into the state-based system which 

is sent to NIOSH annually to be aggregated. 

Sulfur Dioxide: 

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. A summary of symptoms reported is provided in Table 1. Case descriptions for high 

and moderate severity cases are provided in Table 2. 

Page 4 of7 
Table I. SENSOR-Pesticides 1998-2009: Reported 

Health Effects for Sulfur Dioxide Cases 

N=25 

Health Effects # of occurrences 

Dermal 9 

Ocular 9 

Respiratory 13 

Gastrointestinal 4 

Renal 0 

Nervous System 5 

Cardiovascular I 

Misc. 2 

* Cases may report multiple health effects 

Table 2. SENSOR-Pesticides 1998-2009: Sulfur Dioxide Case Detail 

Moderate and Severity Cases 

Case 10 I Severity* I Year I Case Description 

CA07107 High 2000 No description provided 

CA05745 Moderate 1999 No description provided 

Moderate Exposed when walking down a hallway where 

CAI4109 2004 there was fumigation going on in enclosed rooms 

using sulfur dioxide on grapes. 

CA09929 Moderate 200 1 No description provided 

CA02618 Moderate 1998 No description provided 

CAI7156 Moderate 2009 Developed a rash after being exposed to sulfur 

dioxide while filling a tank. 

Moderate Exposed to sulfur dioxide fumes when opening a CAI7110 2009 previously fumigated area. 

CA08 113 Moderate 2000 No description provided 

CA04660 Moderate 1999 No description provided 

CA03954 Moderate 1998 No description provided 

CA07254 Moderate 2000 No description provided 

*SENSOR-Pesticides Severity Index 

I. Death Human Fatality 

2. High Life threatening, requires >5 days lost work/time 

treatment 

3. Moderate Involves systemic effects 3-5 days lost work/time 

4. Minor Symptoms typically <3 days lost work/time 

resolve without 

treatment 

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 

Page 5 of 7 
actiVIties. Limited or missing case detail from the California case reports makes it difficult to 

f~rther 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. 

Sodium Bisulfite: 

A query of SENSOR-Pesticides 1998-2009 identifies a total of 4 cases, stemming from 2 events, 

for sodium bisulfate (pc codes 078201 and 111409). There were three fatalities and one low 

severity case reported. One event(# FL00135) that occurred in a fishing vessel in Florida led to 

the three fatalities. The victims were found in a fishing vessel hold along with ice and sodium 

metabisulfite preservative. Event detail states victims were using the preservative in a poorly 

ventilated area. 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? Sodium 

metabisulfate is also used as a food preservative. In 1993 another (non-SENSOR) case report 

was published about shrimp trawler deaths involving the chemical as a food preservative in a 

ship hull? The 1998 sodium metabisulfite MSDS does contain a hazard statement against using 

the preservative in ship hulls. 

The low severity case occurred in Texas in 2004; the case was exposed when sodium bisulfite 

got onto his skin and resulted in dermal swelling and pain. 

c. Agricultural Health Study (AHS) 

The AHS is a high quality, prospective epidemiology study evaluating the link between pesticide 

use and various health outcomes including cancer. The AHS includes private and commercial 

pesticide applicators and their spouses. If there are AHS findings relevant to a particular 

pesticide going through registration review, the Agency will ensure they are considered in the 

problem formulation/scoping phase of the process and, if appropriate, fully reviewed in the risk 

assessment phase of the process. The AHS includes information on use of 50 different pesticide 

active ingredients commonly used in agriculture. 

2 lbid. 

3 Since the introduction of sodium metabisulfite as a food preservative, it has been associated with several 

idiosyncratic reactions (eg, bronchospasm, oculonasal symptoms, and urticaria/angioedema) in sulfite-sensitive 

individuals. The pathogenic mechanism of these reactions is not yet understood. We report the case of two crewmen 

on a shrimp trawler who were found dead in the ship's hold. Their deaths had occurred while they were applying 

dry sodium metabisulfite, referred to as "shrimp dip" in the shrimping industry. Postmortem examinations showed 

diffuse pulmonary edema consistent with death secondary to asphyxia. Associated findings were visceral congestion. 

Although it is possible to measure deathfi·om sodium metabisulfite with available records, its potential morbidity 

cannot be estimated. It is known that sodium metabisulfite can react with acids and water, releasing toxic sulfur 

dioxide (S02) gas. In addition, S02 gas reacts with respiratory tissue forming sulfureous acid, and inducing a 

pulmonary reaction causing hypoxemia. Furthermore, sodium metabisulfite, compared with sodium bisulfite, has a 

much greater propensity to release S02 gas. We conclude that there is a need for improved education regarding the 

potential side effects of sodium metabisulfite, thus eliminating needless occupational morbidity and mortality. 

Page 6 of7 
Sodium bisulfate and sulfur dioxide are not included in the AHS. 

IV. CONCLUSION 

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. Sodium metabisulfate 

is also used as a food preservative.4 Thesodium metabisulfite MSDS (issued in 1998) does 

contain the following hazard statement, "WARNING! Contact with acids, water or ice releases sulfur 

dioxide gils which may be harmful or deadly if inhaled. Use of this product in confinetl spaces may cause 

suffocation leading to death. Do not use in unventililted areas such as in the holds of fishing boats, walk-in 

coolers or confined spilces. Use only in ventilated areas.,~; 

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. 

4 Ann Allergy. 1993 Dec;71(6):563-6.Sodium metabisulfite and S02 release: an under-recognized hazard among 

shrimp fishermen. Atkinson DA, Sim TC, Grant JA. 5 Sodium Metabisulfite MSDS: http://www.chemone.com/default/msds/Sodium%20Metabisulfite.pdf 

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