UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: December 16, 2014 

SUBJECT: Ziram: Tier I Review of Human Incidents 

PC Code: 034805 DP Barcode: 0424449 

Decision No.: 497363 

Petition No.: NA 

Registration No.: NA 

Regulatory Action: NA 

Risk Assessment Type: NA Case No.: NA 

TXR No.: NA CAS No.: 137-30-4 

MRID No.: NA 40CFR: NA 

FROM: 

Ver.Apr.08 

Toxicology 

Elizabeth Evans, 

and Epidem

Environmental 

iology Branch 

Protection Specialist 

~~ 

_ ~ 

Health Effects Division (7509P) 

and 

Shanna Recore, Industrial Hygienist A ~ "· . . .. " () ~ '""' . "' 

Toxicology 

Health Effec

and 

t Di

Epidemiology 

vision (7509P) 

Branch ~ ~ 

_.,<1 , J / /} / 6 Jcc-wrC( 

THROUGH: David Miller, Acting Branch Chief .Jld //dl::f\. 

Toxicology and Epidemiology Brandi 

Health Effects Division (7509P) 

TO: Marquea King, Risk Assessor 

Risk Assessment Branch IV 

Health Effects Division (7509P) 

and 

Dana Friedman, Chemical Review Manager 

Risk Management & Implementation Branch 2 

Pesticide Re-evaluation Division (7508P) 

Summarv and Conclusions 

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. 

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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. 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 registered 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 is 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 fungicide 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 paint, 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 is to identify potential patterns in the frequency and severity of 

the health effects attributed to ziram exposure. Ziram is in the AHS, and the findings will be 

summarized in this report. 

III. RESULTS/DISCUSSION 

a. IDS (Incident Data System) 

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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 1 992, 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. 

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 IDS, 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 classified as minor severity. 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 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. 

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 this memo. Both 

cases were low in severity. One case involved the off-target movement of the pesticide applied 

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by 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 epidemiology 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 ingredients 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 significant 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 pesticide applicators in the 

AHS (Kamel et al., 2000). EPA notes the potential link between ziram and retinal degeneration 

reported in the AHS population of pesticide applicators but recognizes the preliminary nature of 

these data. The Agency will update its summary 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 

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