UNITED STATES ENVIRONME NTAL PROTECTION AGENCY WASHINGTON, D.C . 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM Date: December 16, 2014 SUBJECT: Z iram : T ier I Review of Human Incidents

PC Co de : 034805 DP Barcode: 0424449 Dec ision No.: 4 97363 Petitio n No.: NA Registration No. : NA Regu latory Action: NA Case No.: NA Risk Assessment Typ e: NA TXR No.: NA CAS No.: 137

- 30- 4 40C FR: NA MRID No.: NA FROM: Ver
.Apr.08 Elizabeth Evans, Environmental P rotection Specialist
_

## ~ Toxicology and Epidemiolo gy Branch

### ~~ Healt h Effects Division (7509P) and Shanna Recore, Industrial Hygieni st A

### ~ "·
. . .. " ()

### ~ '""'
. "' Toxicology and Epidemiology Branch**~ ~**  Health Ef fec t Div i s ion (7509P) 

# _.,<1 , J

# //} / 6 

### Jcc

- 

### wrC( THROUGH: David Miller, Acting Branch Chief 

# .Jld//dl::f\. T oxicolo gy and Epidemiology Brandi Health Effects Division (7509P) TO: Marqu ea King , Ri sk Assessor Ri sk Assessment Branch IV Health Effects Division (7509P) and Dana Friedman, Chemical Review Manager Ris k Management & Imp lementation Branch 2 Pesticide Re-evaluation Division (75 08 P) Summarv and Conclusions Based on the low frequ ency and low severity of cases invol ving z iram reported in both IDS and SENSOR-Pesticides, there does not appear to be a concern at thi s time that would warrant further in ves tigation. The Agency w ill continue to monitor the inc ident information and if a concern i s triggered, additional analysis will be included in the risk assess ment. Page 1 of 4Detailed Review 

### I. ACTION REQUESTED This review is intended to fu lfill 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 ofthe 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. However, 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 Ziram is an agricultural fungicide regi stered to control fungal diseases on a wide range of crops including stone fruits, pome fruits, nut crops, vegetables and commercially grown ornamentals. In addition, it i s formulated as a rabbit repellent for outdoor foliar applications to ornamentals and as an additive in industrial adhesives, caulking, and latex paints. The total annual domestic use of ziram is approximately 1
. 9 million pounds of active ingredient. Ziram was first registered in the United States in 1960 as a broad spectrum use fungic ide to control the scab in apples and pears, leaf curl in peaches, and anthracnose and early blight in tomatoes. In 1981, additional uses were added to the label for controlling leaf blight and scab in almonds, shot-hole in apricots, brown rot and leaf spot in cherries, scab and anthracnose in pecans, and leaf spot , rust and powdery mildew in ornamentals. Other registered uses of ziram include homeowner application on residential ornamentals as a rabbit repellent and industrial application as a preservative in exterior latex pa int, caulking, sealants and wall boards. For this evaluation, both 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-Pesticides (SENSOR) databases were consulted for pesticide incident data on the active ingredient ziram (pc code : 034805). The purpose of the database search i s to identify potential patterns in the frequency and severity of the health effects attributed to z iram exposure. Ziram is in the AHS, and the findings will be summarized in this report. 

### III. RESULTS/DISCUSSION
a. IDS (Incident Data System)

Page 2 of4OPP ' 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 in cidents 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 lo cation, date and nature of the incident. Main ID S 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.


### 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
. For the Main ID S, from January I, 2009 to August 12,2014, there were 0 incidents reported involving ziram in the database. In Aggregate IDS , from January 1, 2009 to August 12, 2014, there were 2 incidents reported involving ziram in the database. These incidents were classi fied as minor sever ity. Overall, there are few incidents involving ziram reported to IDS. 

### b. SENSOR-Pesticides The SENSOR-Pesticides database covers 11 states from 1998-2010 , 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 ofparticular value in providing that information. The state coordinator at each of the 1 1 respective state Departments of Health conducts case followup activities such as obtaining medical records to verify symptoms and sever ity . 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. A query of SENSOR-Pesticides from 1998-20 l 0 identifies 16 cases involving ziram (pc code 034805); 2 cases involved a single active ingredient and were analyzed for th is memo. Both cases were low in severity. One case involved the off-target movement of the pesticide applied
Page 3 of4by a homeowner onto a neighbor. This case experienced a headache. One case involved an agricultural worker exposure. This occupational case experienced dizziness, ocular pain and gastrointestinal symptoms.



### c. Agricultural Health Study (AHS) The Agricultural Health Study (AHS) is a high quality, prospective epidem iology study evaluating the link between pesticide use and various cancer and non-cancer health outcomes. The AHS includes private and commercial pesticide applicators and their spouses. The AHS includes information on use of 80 different pesticide active ingredi ents commonly used in agriculture. Regarding ziram, there is one AHS investigation which reports a positive link between lifetime ziram exposure and an adverse health outcome. Kirrane et al. (2005) reported a non-statistically s ignificant association between ever use of ziram and retinal degeneration among wives of AHS pesticide applicators (odds ratio 1.5 (95% confidence interval 0.40, 5.0)). This finding is consistent with previous research within the AHS cohort that linked lifetime fungicide (overall) use and risk of retinal degeneration among male pest icide applicators in the A HS (Kamel et al., 2000). EPA notes the potentia l link between ziram a nd retinal degeneration reported in the AHS population of pesticide applicators but reco gnize s the preliminary nature of these data. The Agency will update its summa ry and review of the epidemiological literature concerning ziram during regulatory review.


### IV
. CONCLUSION Based on the low frequency and low severity of cases involving ziram reported in both IDS and SENSOR-Pesticides, there does not appear to be a concern at this time that would warrant further investigation. The. Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be included in the risk assessment.
Citations Kamel, F. , Boyes, W. K., Gladen, B. C., Rowland, A. S., Alavanja, M. C., Blair, A., & Sandler , D. P. (2000). Retinal degeneration in licensed pesticide applicators. Am J Ind Med, 37(6), 618-628. Kirrane, E., Hoppin, 

### J., Kamel, F
. , Umbach, D., Boyes, W., DeRoos, A.,
... Sandler , D. (2005). Retinal degeneration and other eye disorders in wives of farmer pesticide applicators enrolled in the agricultural health study. American Journal of Epidemiology, 161 (11 ), 1020-1029. doi: 10.1093/aje/kwi140

Page 4 of4