UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , D.C. 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION MEMORANDUM Date: May 1, 2013 SUBJECT: 

### Sulfur. Summary of Human Health Risk Assessments to Support Registration Review PC Codes: 077501 DP Barcode: 0405975 Decision No.: 470688 Petition No.: Not Applicab le Registration No.: Not Applicab le Regulatory Action: Registration Review Risk Assessment Risk Assessment Type : Single Chemical Aggregate TXR No.: Not Applicable Case No. : 0031 CAS No. : 7704-34-9 MRID No.: None 40 CFR: 180.1236

FROM:

THROUGH:

TO: Angela Howard, PhD, Toxicologist/Risk Assessor

## ~**~** Kelly O'Rourke, Bio logist/Risk Assessor

### 11**·t- ~**  /l 1 

# v'

.**~L** Bonnie Cropp-Kohlligian, Environmental Scient ist ·

## u.A' cU\ -'()

## 1~t 

# IJRisk Assessment Branch 

### IV Health Effects Division (7509P) Office of Pesticide Programs Elissa Reaves , PhD, Branch Chief Risk Assessment Branch 

### IV Health Effects Division (7509P) Office of Pesticide Programs Jose Gayoso, CRM Risk Management and Implementation Branch II Pesticide Re-evaluation Division (7508P) Office of Pesticide Programs

Attached is a qualitative human health risk assessment to support registration review for elemental sulfur as an active ingredient in pesticide formulations. HED has not required additional mammalian toxicity data for sulfur and did not conduct a quantitative risk assessment for dietary, residential, occupational, or aggregate risk.

Page 1 of7

### 1.0 

### 2.0 3

.0 4.0 5.0 6.0 

### 7.0 8.0 9.0 10

. 0 Executive Summary Regulatory Recommendations Introduction Hazard Identification and Dose-Response Assessment Dietary Exposure and Risk Assessment Residential (Non

- Occupational) Exposure/Risk Characterization Aggregate Exposure/Risk Characterization Cumulative Exposure/Risk Characterization Occupational Exposure/Risk Characterization References

Page 2 of7 

### 3 3 4 5 

### 6 6 6 6 7 

### 7

### 1.0 Executive Summary HED has prepared a human health risk assessment to support registration review for the uses of e lemental sulfur ("sulfur" for the remainder of this memorandum) as an active ingredient in pesticide formulations. Because of the low toxicity of su lfur to mammals, HED determined that a qualitative risk assessment is appropriate. Su lfur is a fungicide/miticide/insecticide which is currently regi stered for use on a variety of field crop s, fruits, vegetables , ornamentals , lawns , and golf courses. It is formu lated into dusts (20

- 99.8% active ingredient), wettable powders , and flowable concentrates. There is potential for occupational and residential exposure during handling and postapplication activities. Curren t available toxicity studies and the literatur e do not indicate any system ic toxicity associated with sulfur exposure and no endpoints of toxicological concern have been identified fo r risk assessment purposes. The acute toxicity of sulfur is low. Acute oral toxicity is category IV , while acute dermal and inhalation are category III. Sulfur is an eye and skin irritant (Category III), but is not a skin sensitizer. A review of incident data indicates that both the relative number ofreported incidents and the severity of reported health effects are low. In general, the dermal, ocular and respiratory symptoms/health effects are reflective ofthe known irritating properties of sulfur. A 24-hour restricted entry interval (72 hrs in Ca lifornia) i s established for fo liar applications, and occupat ional handlers are required to wear personal protective equipment such as coveralls, chemical-resistant gloves , and goggles during mixing/loading and application. Sulfur is classified as List 4A (minimal risk inert ingredient). Based on the low toxjcity of sulfur to mammals, it is currently exempt from the requirement of a tolerance. Concern for residential and occupational exposure is low because the labels specify adequate measures to protect from the irritating effects of sulfur. While exposure to su l fur is possible via the diet, as well as residential and occupationa l use patterns, HED has not identified any toxicologic al endpoints for human health risk assessment. Therefore, HED concludes that no quantitative dietary, residential, aggregate or occupational risk assessments are needed. Sulfur does not belong to a common mechanism group , and therefore there are no cumulative risk concerns. No human studies were used in the sulfur risk assessment. 

### 2.0 Regulatory Recommendations Sufficient data are available to support HED's decision to waive generic mammalian toxicity data requirements for su lfu r. Residues of sulfur are exempt from the requirement of a tolerance under 40 CFR 

### § 180.1236 when used in accordance with good agricultural practices. Codex has not estab li shed maximum residue limits for sulfur. Concern for residential and occup ational exposure is low because the

Page 3 of7labels specify adequate measures to protect from the irritating effects of sulfur. Therefore, HED has no objection to the continuing registration of sulfur for current uses. 3 .0 Introduction Sulfur is a naturally occurring, ubiquitous element in the environment that is also essential to the human body and needed at relatively high levels. Sulfur is a fungicide/miticide/insecticide which is currently registered for use on a variety of field crops, fruits , vegetables, ornamentals, lawns, and golf courses. It is formulated into dusts (20-99.8% ai), wettable powders , and flowable concentrates. Sulfur is also mixed with other pesticides/compounds and formulated into liquids or powders. There are several registered gas cartridge products where sulfur is mixed with potas sium nitrate and carbon. These gas cartridge products (sulfur, potassium nitrate and carbon mixtures) are designed to undergo chemical reactions and produce toxic fumes after ignition. A lthough no toxicity data are available on the fume by products, HED believes that worker and bystander exposure scenarios are not likely to exist based on the use patterns (underground uses) and current label precautions. This registration rev iew document is for the sulfur active ingredient only. Although considered a low toxicity pesticide, elementa l sulfur is moderately irritating to the skin and is associated with occupationally related irritant dermatitis, and airborne dust is irritating to the eyes and the respiratory tract. For the current action, a search ofthe open literature was conducted to identify any new toxicity studies since HED' s 2009 memorandum: "Sulfur. Human Health Risk Scoping Document 

### in S upport ofRegistration Review

- Addendum" (0361 061, R. Kent, 1129/2009). None were found to be critical such that a quantitative assessment would be requ ired. Additionally, updated incident data indicate that the risk posed to human health by sulfur appears low , and there does not appear to be a concern at this time that would warrant further investigation. The Agency will evaluate any additional incident information that is submitted during the comment period and ifa concern is triggered during that time, additional analyses will be conducted. Potential areas of environmental justice concerns, to the extent possible, were considered in the 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." The Office ofPesticide Programs (OPP) typically considers the highest potential exposures from the legal use of a pesticide when conducting human health risk assessments, including, but not limited to, people who obtain drinking water from sources near agricultural areas, the variability of diets within the U.S., and people who may be exposed when harvesting crops. Should t hese highest exposures indicate potential risks of concern, OPP further refines the risk assessments to ensure that the risk estima tes are based on the best available information.

Page 4 of7

### 4

.0 Hazard Identification and Dose-Response Assessment The toxicology database for sulfur is adequate to support Registration Review. To date, EPA has not required additional mammalian toxicity data for sulfur based on the long history of safe use, the low acute toxicity and the ubiquitous natural occurrence of sulfur in the environment. Acute toxicity studies via the oral, dermal and inhalation routes in rats have been conducted with technical sulfur. Sulfur is Category III via the dermal and inhalation routes, and Category IV via the oral route. The oral LDso is greater than 5000 mg/kg b.w

. and the dermal LD 50 is greater than 2000 mg/kg b.w. in rats. The inhalation LCso is greater than 2.56 mg/L for a 4-hour exposure. Topical application of sulfur to rabbit skin resulted in well defined to moderate erythema and slight edema at 24 and 48 hours. A primary eye .irritation study in rabbits shows sulfur to be an eye irritant. Sulfur is not a skin sensitizer. Rats exposed to sulfur via inhalation exhibited body weight depression, decreased blood sulfhydryl content, decreased serum peroxidase levels and increased serum albumin. A 28-day dermal toxicity study did not find any treatment-related changes in hematological and biochemical parameters, organ weights and their ratios in either sex. The only finding was a significant increase in the incidence ofhyperkeratosis observed microscopically in males and females at 1000 mg/kg/day, the highest dose tested. No chronic, reproductive or developmental studies were identified in the literature, however, there are no known risks of oncogenic, reproductive, or developmental hazards associated with sulfur. The genotoxic potential of sulfur dust was tested in vitro in bacteria and mammalian cells and technical sulfur was tested in vivo in a micronucleus assay in mice

. Sulfur did not induce any genotoxicity in any ofthe systems tested. From the available database, there is no evidence to suggest increased susceptibility in infants and children. Since sulfur is a naturally occurring, ubiquitous essential element, and since the dietary contribution of sulfur from pesticidal uses to the total diet is expected to be low, the additional tenfold FQPA safety factor for the protection of infants and children is unnecessary. A search of the open literature did not identify any new toxicity data considered critical such that a quantitative assessment would be required. Updated incident data indicate that the risk posed to human health by sulfur appears low, and there does not appear to be a concern at this time that would warrant further investigation. In summary , sulfur is a naturally occurring element that is essential to the human body and needed at relatively high levels. Current available toxicity studies and the literature do not indicate any systemic toxicity associated with sulfur exposure and no endpoints oftoxicological concern have been identified for risk assessment purposes. Therefore, dietary, residential, and occupational risk assessments have not been conducted. The human risks from both dietary and residential/occupational exposure to sulfur are considered to be very low.

Page 5 of7

### 5

.0 Dietary Exposure and Risk Assessment Residues of sulfur are exempt from the requirement of a tolerance under 40 CFR 

### § 180.1236 when used in accordance with good agricultural practices. Sulfur occurs naturally in food and is abundant in the environment. Residue chemistry studies have not been submitted, and none are required. While exposure to sulfur could occur via the diet, re sidues from the pesticidal uses are not likely to exceed the levels naturally occurring in food and water. In addition, HED has not identified any toxicological endpoints to conduct a human health risk assessment. Therefore, no additional data are required and no quantitative dietary assessments are needed. 

### 6.0 Resident ial (Non-Occupational) Exposure/Risk Characterization While exposure to sulfur could occur in the residential environment, HED has not identified any toxicological endpoints to conduct a human health risk assessment. HED has no objection to the continuing registration of sulfur because there are adequate label recommendations regarding potential eye and skin irritation. 

### 7.0 Aggregate Exposure/Risk Characterization HED has no concern for aggregate risk resulting from the existing uses of sulfur given the lack of toxicity and in light of the natural prevalence ofthis essentia l nutrient in the environment. While both residential and dietary exposures are po ssible given the use pattern, HED has not identified any toxicological points of departure needed to conduct a quantitative human health risk assessment. 

### 8.0 Cumulative Exposure/Risk Characterization Section 498(b)(2)(D)(v) ofFFDCA require that, when considering whether to establish, modify, or revoke a to lerance, the Agency considers "ava ilable inf ormat ion " concerning the cumulative effects of a particular pesticide ' s residues and "other substances that have a common mechanism oftoxicity." 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 fmding as to sulfur. In addition, sulfur does not convert to toxic metabolites resulting in other substances. For the purposes of this registration review, therefore, EPA has not assumed that sulfur has a common mechanism oftoxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism oftoxicity 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 /

.

Page 6 of7

### 9.0 Occupational Exposure/Risk Characterization Occupational exposure to sulfur is possible due to the registered use pattern. While exposure to sulfur could occur in occupational settings , HED has not identified any toxicological endpoints to conduct a human health risk assessment. Although no systemic toxicological endpoints were identified for sulfur, incidents related to its irritating properties (primarily skin and eye) were noted among field workers re-entering treated fields in California. To address this, a qualitative occupational risk assessment was conducted previously which recommended that a 24-hour restricted e ntry interval (REI) for foliar applications be establi shed. The assessment also recommended that occupational handlers should wear personal protective equipment (PPE) such as coveralls, chemical-resistant gloves , and goggles during mixing/loading and application based on the Ca lifornia incident data. The addition of respirators is not warranted because, based on the data, most incidents involved workers re-entering treated fields; the requirement of a respirator is not enforceable once the 

### REI has expired. All label requirements previously recommended have been adequately incorporated into the most current sulfur product labels.



### 10.0 References
Table 10

. 1. Memoranda Relevant to Registration Review Risk Asses sment Author Barcode Da te Title M. Rogoff None 2/4/ 1976 Waiver of Data- Elemental Sulfur W. Greear None 7/2511990 Toxicology Summary for the FY ' 90 Reregi stration Decision on Su lfur P

. Perreault None 7/20/1 9900 Assessment of Reentry /Non-D ietary Exp osure Data Requirements For Sulfur and Recommendation s For The Reregistration Decision Document 10M N/A 2005 Dietary reference intakes for Water, Potassium, Sodium Chloride , and Sulfate . Washington DC: Food and Nutrition Board Institute of Med icine European Un ion N/A 3/ 1 /2008 Draft Assessment Report (Public Version): Su lphur. Vol3, Annex B , Part 2 /A, B.6. Y. Donovan D346937 1 /17 /2008 Sulfur (PC code 077501). Human Health Risk S coping Document in Support of Registration Revi ew R. Kent D361061 1/29/2009 Sulfur. Human Health Risk Scoping Document in Support of Regi stration Review

- Addendum J. Melendez D402561 10 / 12/2012 Rationale for Not Conducting a Drinking Water Analysis for Elemental Sulfur for Human Health Risk assessment as a Result of Applications of the Chemical as a Fungicide/lnsecticide S. Recore D410259 3/2 1 /2013 Sulfur: Updated Revi ew of Human Incidents

Page 7 of7