UNITED STATES ENV IRONM ENTAL 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: 04 11 76 1 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 Protect ion Specia li st rrr ·

# ""~ To xic ology and Epidemiology Branch 

# q/v

# ~ Health Effects Division (7509P) 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, Chemica l Review Manager Risk Management & Implementation Branch VII Pestic ide Reevaluation Division (7508P) and C. Cyran, Chemical Review Manager Risk Management & Implementation Branch VII Pesticide Ree valuation Division (7508P)

Page 1 of7Summary 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 trigg ered, additional analysis will be incl uded 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 pro vide 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 ofregistration 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 T he inorganic sulfites reregistration case includes the chemicals sulfur dioxide (CAS No. 7446- 09-5) and sodium metabi sulfite (CAS No. 7681-57-4). As active ingredients , these chemicals are fungicides typically used to treat for Botrytis cinerea, the fungus which causes bunch ro t, 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. T he pads absorb moisture generated by grapes, and release low levels of sulfur dioxide in the range of 1-5 ppm. En d-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 searc h / reg actions/reregistration/ red G-50 1-Mav

07. pdf Page 2 of7For this evaluation, the OPP Incident Data System (IDS) and the Centers for Disease Control and Prevention/National Institute fo r 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). Additionall y, the California Department of Pesticide Regulation (CDPR) Pesticide Illness Surveill ance Program (PISP) was queried for this scoping document in order to supplement the SENSORPesticide data for sulfur dioxide. Generally the T ier I incident scoping documents do not include a query ofPISP. However several SENSOR cases, all from California, did no t include a descriptive narrative making it difficu l t 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 St udy (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 In sect icide, Fungicide and Rodenticide Act (FIFRA) Section 6(a)(2) reports from registrants, other federal and state health and environmental agencies, and individu al 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 anecdo tal reports or a ll egation s only, unless otherwise stated in the report
. IDS records incidents in one of two modules: Main ID S and Aggregate IDS:



### o Main IDS contains incidents resulti n g in higher severity outcomes and provides more detail wi th regard to case specifics. This system stores incident data for death, major and moderate incidents, and it inc ludes information about the location, date and nature of the incident. Main IDS incidents involving only one active ingredient (as opposed to pesticide p roducts with multiple active ingredien ts) are considered to provide more certa in informat ion about the potential effects of exposure from the pesticide.

Page 3 of7o 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 19,20 1 3, there were no repo rted 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 severi ty. Us ing 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 1 998

- 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. Resp iratory 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 of7Table 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 Ca rdiovascular I Misc. 2 

### * Cases may report multiple h ealth 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 H igh 2000 No descriptio n provided CA05745 Moderate 1999 No description provided Moderate Exposed when walking down a hallway where CAI4109 2004 there was fumigation going on in enc losed room s using su lfur dioxide on grapes . CA09929 Moderate 200 1 No description provided CA02618 M oderate 1998 No description prov ided CAI7156 Moderate 2009 Deve loped a rash after bei ng exposed to sulfur dioxide while fillin g a tank. Mode r ate Exposed to sulfur dioxide fumes when opening a CAI7110 2009 previou s ly fumigated a rea. CA08 1 13 Moderate 2000 No description provided CA04660 Moderate 1999 No description provided CA03954 Moderate 1998 No description provided CA07254 Moderate 2000 No description provided *S ENSOR-Pesticides Severity Index I. Death Human Fatality 2. High Life threatening, requires >5 days lost work/time treatme nt 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 app lication at the time they were exposed; three cases were applying the pesticide, five cases were mi xing or load ing the pes tic ide, and the rema ini ng three were condu cting unknown work Page 5 of 7actiVIties. Limited or missing cas e 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 no t present a risk of concern at this time. Sodium Bisulfite: A query of SENSOR-Pesticides 1998-2009 identifies a to tal of4 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 ic e 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 i s 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. T he AHS includes private and commercial pesticide applicators and their spouses. If there are AHS findings relevant to a particular pes ticide going through registration review, the Agency will ensure they are considered in the problem formulation/scoping phase of the process and, if appropri ate, 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 afoodpreservative, it has been associated with several idiosyncratic reactions (eg, bron cho spasm, oculonasal symptoms, and urticaria /ang ioedema) in sulfite-sensitive individuals. The pathogenic mechanism of these reactions is notyet understood. We report the case of two crewmen on a s hrimp trawler who were found dead in the ship's hold. The ir 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, itspotential morbidity cannot be esti mated. It is known that sodium metabisulfite can react with acids and water, releasing toxic sulfu r 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 of7Sodium bi sulfate 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 follow ing hazard statement, "WARNING! Contact with acids, water or ice releases sulfur dioxide gils which may be harmful or deadly 

### ifinhaled. 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 bi sulfate at thi s time.

4 Ann Allergy. 1993 Dec;71(6):563-6.Sodium metabisulfite and S02 re lease : an under-recognized hazard among shrimp fishermen. Atkinson DA, Sim TC, Grant JA

. 5 Sodium Metabisulfite MSDS: http: //www.chemone.com / defau lt/msds/ Sodium%20Metabisulfite.pdf Page 7 of7