UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM

Date: January 22, 2013

SUBJECT: Atraz in e, Propazine and Simaz i ne: Review of Human Incidents

PC Code: 080803

, 080808

, 080807 Decision No.: 472846 Petition No.: NA Risk Assessment Ty pe: NA TXRNo.:NA MRID No.: NA DP Barcode: 0407491 Registration No.: NA Regulatory Action: NA Case No.: NA CAS No.: 1912-24-9

, 139-40-2, 122-34-9 40CFR: NA

FROM: Shanna Recore, Industria l H ygienist Toxicology and Epidemiology Branch Health Effect Division (7509P) and Ver.Apr

. 08



# - Elizabeth Evans, Environmental Protection Spec i alist "'-)

THROUGH:

TO: T oxicology and Epidemiology Branch**·** · 

## fJ**~~** Health Effect Division (7509P) 

# 12 ·

r

## ~**~~JYl** David Miller, Acting Branch Chief 

# r-j .iJh**~** Toxico l ogy and Epidemiology Branch Health Effects Division (7509P)

Seyed Tadayon, Risk Assessor Risk Assessment Branch V Health Effects Division (7509P) and Molly Clayton, Chemical Review Manager Risk Management & Implementa t ion Branch III Pesticide Re-evaluation Division (7508P)

Summary and Conclusions

Based on the low frequency and severity of incident cases reported for atraz i ne, propazine and simazine in both the IDS and NIOSH SENSOR-Pesticides databases, there does not appear to be

a concern at this time that would warrant further investigation. However, based on current AHS findings for atrazine, we intend to further evaluate follow-on studies from the AHS. In addition,

Page 1 of9the Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be also be included at that time.

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, causa t ion 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

Atrazine, propazine and simazine are chlorinated triazine herbicides. Atrazine is currently registered for use against broadleaf and some grassy weeds. Atrazine is used on corn (field and sweet), guavas, macadamia nuts, sorghum, sugarcane, range grasses under USDA's Conservation Reserve Program (CRP), and wheat (where application is to wheat stubble on fallow land following wheat harvests; wheat is not the target crop). Atrazine is also used in conifer forests, on Christmas tree farms and on sod farms, golf courses and residential lawns. Propazine is a systemic herbicide that is usually applied to the soil, absorbed through leaves and roots, and acts by inhibiting photosynthesis within the targeted plant. It is used as a selective herbicide to control most annual grasses and broadleaf weeds before the weeds emerge or after removal of weed growth. Propazine is registered for use on container-grown ornamentals in greenhouses. Simazine is used pre-emergence for control of broad-leaved and grassy weeks on a variety of deep-rooted crops such as artichokes, asparagus, berry crops, broad beans, and citrus and on non-crop areas such as farm ponds and fish hatcheries.

For this evaluation, both 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 ingredients atrazine, propazine and simazine (PC Codes 080803, 080808, and 080807). The purpose of the database search is to identify potential patterns in the frequency and severity of the health effects attributed to atrazine, propazine or simazine exposure.

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### Page 3 of 9

The Agricultural Health Study (AHS) is a high quality, prospective epidemiology study evaluating the link between pesticide use and various health outcomes including cancer. Atrazine is i ncluded in the AHS and provide s information for this report.

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 Ro denticide Act (FIFRA) Section 6(a) (2) reports from registrants, other federal and state health and environmental agencies

, and individual consumers. Since 1992, OPP has compile d these reports in IDS. IDS contain s reports from across the U.S. and most inci dents 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 specific. This system stores incident data for death, major and moderate incidents, and it includes information about the location, date and nat ure of the incident. Main IDS incidents involving only one pesticide 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

. The Main and Aggregate IDS findings for atrazine, propazine, and simazine are presented below:

Atrazine: For the M ain IDS, from January 1, 200 7 to December 11 , 2012

, there were 18 incidents reported for single chemical only in the database

. Two of these incidents were classified as major severity and are described further in Table 1. Sixteen incidents were classified as moderate severity. There were 23 additional incidents reported involving more than one chemical. Overall, there are few incidents involving atrazine reported to IDS.

In A ggregate IDS , from January 1, 200 7 to December 11 , 2012

, there w ere 102 reported incident s involving atrazine

. These incidents were classified as m inor severity.

Propazine: For the Main IDS, from January 1, 2007 to December 11 , 2012, there were no incidents involving propazine in the database.

In A ggregate IDS , from January 1, 200 7 to December 11 , 2012

, there were no reported incident s involving propazine in the database

.

### Page 4 of 9

Simazine: For the M ain IDS, from January 1, 200 7 to December 11 , 2012

, there were 3 incidents reported for single chemical only in the database. One of these incidents w as classified as major severity and is described further in Table 1. Two incidents were classified a s moderate severity. There

was 1 additional incident reported involving more than one chemical. Overall, there are few incidents invo lving simazine reported to IDS.

In A ggregate IDS , from January 1, 200 7 to December 11 , 2012

, there w ere 3 reported incident s involving simazine

. These incidents were classified as minor severity.

b. NIOSH SENSOR

The NIOSH SENSOR 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’
compen sation claims when reported by physicians, reports from Stat e Departments of Agriculture, and physician reports to s tate Departments of Health . Although both occupational and non

- occupational incidents are included in the database, SENSOR focuses on occupa tional pesticide incidents, and is of particular value in providing that information. A state SENSOR contact specialist attempts to follow

- up with cases and obtains medical records to verify symptoms, circumstances surrounding the exposure, severity, and o utcome. Using standardized protocol and case definitions derived from poison center reporting, SENSOR coordinators at State Departments of Health enter the incident interview description provided by the case , medical report, physician and patient into the SENSOR data system . The SENSOR data system is accessible to participating states and EPA.

Atrazine: In NIOSH SENSOR from 1999 to 2009 there are 115 cases for atrazine stemming from 61 atropine exposure events. Atrazine was the single active ingredient i mplicated in 35 cases. Most (101) cases were classified as low severity , 13 cases were classified as moderate severity and 1 case was classified as high severity. R espiratory symptoms were the most frequently reported health effect (n=61) followed by sym ptoms related to the nervous system (n=57) (Table 2)

. Twenty four cases were exposed at their place of work. Seventy nine cases (69%) were exposed to pesticides via drift

.

Table 2. SENSOR

- Pesticides 1998

- 2009: Reported Health Effects for Atrazine Case s*
Dermal 38
Ocular 46 Respiratory 61
Gastrointestinal 37
Renal 0 Nervous System 57
Cardiovascular 5
Misc. 15

### Page 5 of 9

* Cases may report mu l t iple health

effects



### Activity at the time of exposure The a ctivity at the time of exposure included both occupational and non

- occupational activities which break down as follows: 44 cases were conducting routine nonoccupational outdoor living activities at the time of exposure; 4 of these were moderate in severity and 40 were low in severity. Of these 44

cases , 36 were attributable to drift. 30 cases were conducting routine nonoccupat ional indoor living activities; one of these cases was high in severity, four were moderate in severity and 25 were low in severity. O f these 30 cases

, 26 were at tributable to drift. 17 cases were exposed while applying the pesticide, six of these were occupational and the majority of the remaining cases involved residents making lawn applications. One case was moderate in severity and 16 were low in severity. 15 c ases (all occupational) were conducting rou tine work, including field work; two of these 15 cases were moderate in severity and 13 were low in severity. This group included one event where 11 field workers were exposed to drift from an aerial application on an adjacent field ; event details are provided below.

Multiple case events There are several multiple case events involving atrazine. Events involving ten or more cases are summarized here. In Florida in 2004, 18 symptomatic cases were reported after a pest control operator applied multiple pesticides, including atrazine, at the wrong location. One of these cases was moderate in severity and 17 were low in severity. Another event which occurred i n Louisiana in 2002, 10 symptomatic cases were reported after being exposed to aerial drift from a multiple pesticide herbicide application made to a sugarcane field adjacent to the residence. Cases reported a variety of symptoms including coughing, sneezing, nausea, vomiting, diarrhea, eye and skin irritatio n, difficulty breathing, and dizziness. All 10 cases were low in severity. Finally, in Washington State in 2005, 11 greenhouse workers were made ill after being exposed to drift from an herbicide application. One of these cases was moderate in severity and 10 were low in severity.

Propazine: A query of SENSOR

- Pesticides 1998

- 2009 finds no reported cases for propazine.

Simazine: A query of SENSOR

- Pesticides 1998

- 2009 finds 20 reported cases for simazine stemming from 19 simazine exposure events. Five cases involved simazine as the single active ingredient. Seventeen cases were work

- related. There was one case classified as high severity, four cases classified as moderate severity and 15 cases classified as low severity. Eight cases were exposed whi le applying a pesticide. The effects reported include respiratory, ocular, nervous system, gastrointestinal, cardiovascular, and dermal (Table 3).

### Page 6 of 9

Table # 3 . SENSOR

- Pesticides 1998

- 2009: Reported Health Effects for Simazine Cases*
Dermal 8
Ocular 10 Respiratory 8
Gastrointestinal 3
Renal 0 Nervous System 11
Cardiovascular 1
Misc. 2 * Cases may report mu l t iple health

effects



### 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 en sure 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

. Since the time of the last evaluation of epidemiological literature pertaining to atrazine (Sept. 2010 non

- cancer effects, and July 2011 cancer effects) there have been four new studies published in the peer review literature that merit f urther consideration in the registration review/risk assessment process. Each study extends work included in the previous evaluation by EPA, specifically adverse birth outcomes, and menstrual cycle characteristics in association with environmental exposure to atrazine. Craigin et al. (2011) performed a cross

- sectional analysis of atrazine exposure and menstrual cycle characteristics among a cohort of women residing in Illinois (high atrazine use area) and Vermont (low atrazine use area). Authors measured at razine exposure using three different metrics of individual

- level exposure, requested participants compile a menstrual cycle diary, and measured urinary concentration of steroid hormone levels. Overall, this work supports and extends the previously publish ed studies by Farr et al. (2004) using Agricultural Health Study data. Craigin et al. (2012) reported associations with menstrual cycle irregularities, but not cycle length, absence of cycle, or intermittent bleeding. Authors also showed a link with certai n hormone levels and atrazine exposure including estradiol metabolites during the LH surge of the cycle. A full evaluation of this study will take place during the preparation of the risk assessment.

Additionally, two study groups evaluated aggregate leve l atrazine exposure (proximity of maternal residence to agricultural area and/or drinking water monitoring site) and pre

- term birth

### Page 7 of 9

and an adverse birth outcome (choanal atresia and stenosis), respectively (Rin sky et al. 2012 and Agopian et al. 2012). Both study groups reported statistically significant positive association with measures of atrazine exposure, and the use of aggregate level exposure measures is noted. Chevrier et al. (2011) evaluated birth characteristics in association with atrazine exposur e in a prospective birth cohort located in Brittany, France. Authors performed individual

- level exposure assessment (urinary concentration of atrazine) taken mid

- point in pregnancy. Researchers reported an approximate 50% increase in fetal growth restricti on and small head circumference among the cohort participants, but no association with major birth defects was reported.

EPA will evaluate these new additions to the observational data base regarding adverse health effects as a result of environmental ex posure to atrazine, and integrate these findings with the other studies already reviewed and presented to the public at the FIFRA Science Advisory Panel in September 2010.

Propazine and simazine are not included in the AHS.

IV. CONCLUSION

Based on the low frequency and severity of incident cases reported for atrazine, propazine and simazine to both IDS and NIOSH SENSOR

- Pesticides

, there does not appear to be a concern at this time that would warrant further investigation

. However, based on current AHS findings for atrazine we intend to further evaluate follow

- on studies from the AHS . In addition, t he Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be also be included at that time.

Citations :

1: Agopian AJ, Cai Y, Langlois PH, Canfield MA, Lupo PJ. Maternal Residential Atrazine Exposure and Risk for Choanal Atresia and Stenosis in Offspring. J Pediatr. 2012 Oct 1. doi:pii: S0022

- 3476(12)00929

- 8. 10.1016/j.jpeds.2012 .08.012. [Epub ahead of print] PubMed PMID: 23036484.

2: Rinsky JL, Hopenhayn C, Golla V, Browning S, Bush HM. Atrazine exposure in public drinking water and preterm birth. Public Health Rep. 2012 Jan

- Feb;127(1):72

- 80. PubMed PMID: 22298924; PubMed Centra l PMCID: PMC3234399.

3: Cragin LA, Kesner JS, Bachand AM, Barr DB, Meadows JW, Krieg EF, Reif JS. Menstrual cycle characteristics and reproductive hormone levels in women exposed to atrazine in drinking water. Environ Res. 2011 Nov;111(8):1293

- 301. doi: 10.1016/j.envres.2011.09.009. Epub 2011 Oct 13. PubMed PMID: 22000761.

4: Chevrier C, Limon G, Monfort C, Rouget F, Garlantézec R, Petit C, Durand G, Cordier S. Urinary biomarkers of prenatal atrazine exposure and adverse birth
outcomes in the PELAGIE birth cohort. Environ Health Perspect. 2011 Jul;119(7):1034

- 41. doi: 10.1289/ehp.1002775. Epub 2011 Mar 2. PubMed PMID:

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21367690; PubMed Central PMCID: PMC3222984.

### Page 9 of 9

T able 1. Main IDS Major Incidents
Human Incident Chemical: Atrazine PC Code: 080803

Incident Package Report Incident

Date Location Reg Number Product Name Exposure Severity Codes Incident Description

018825

- 00038 7/3/2007 LA NA ATRAZINE HB A 66 year old male applied the product on top of gasoline to treat his property. It caught on fire and he inhaled the fumes. He was takes to a local health care facility and treated for shortness of breath, shakiness,

an d headache. He also had an EKG and CT and treated with steroids which improved his breathing. He was transferred to a hospital and eventually an ICU.

019218

- 00015 1/1/2007 FL 000538

- 00229 SCOTTS BONUS

S WINTERGUARD SOUTHERN WEED AND FEED FERTILIZER PLUS HERB HB An adult female reports that her husband and neighbor have used the product for years. She suspects that she and her husband are getting poisoned by the product because of a crack in her water line. She has been experiencing dry mouth, food not tasting ri ght, and Paresthesia of the lips and hands. She has been to the ER multiple times over the last year with these ailments. Her husband has experienced mental sluggishness, kidney failure, and throat cancer. Human Incident Chemical: Simazine PC Code: 080807

019115

- 00001 10/30/2007 SILVER SPRINGS, TX 034704

-

00687 SIMAZINE 4L

FLOWABLE HERBICIDE HB An 8 year old male played soccer on a field that had been treated with the product a week prior. He experienced respiratory arrest and was hospitalized overnight. He had an appointment to follow

- up with Children's Medical Center. *HB

- Human Major (if the person alleged or exhibited symptoms which may have been life

- threatening, or resulted in adverse reproductive effects or in residual disability)