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Atrazine Focus Meeting 

July 25 2013 July 25, 2013

Slides enclosed for following agenda items

● Agricultural and non-agricultural use sites, clarification of non-ag use 

sites; (fallow, hay, pasture, forests, turf, conservation reserve program) 

● Other label clarification/harmonization 

● Brief overview of stewardship programs 

● Topics for future discussion

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● Additional data to be submitted
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Atrazine Use Sites

A table summarizing all atrazine labeled uses is being

prepared.

Draft copies are provided. 

Intended to include all uses from the technical 

registrants’ atrazine end use labels

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atrazine end use labels

Use and Survey information

Example of Areas For Label 

Clarification/Harmonization

● Fallow Uses

● CRP P t H CRP, Pastures, Hay

- For establishing grasses, grazing/haying 

prohibition

● Roadsides, Rights-of-Way (lumber yards, ...)

● Conifers / Forestry

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Statements in EPA Label Data Report for 

Atrazine and Problem Formulation for 

Environmental Fate and Ecolological Risk 

Assessment for Atrazine

● Some listed rates appear to be incorrect

● Some listed use sites are not on current labels

- i.e. soybean, wheat, oats – there are fallow uses 

after harvesting these crops or use in the year 

before planting these crops.

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● Plan to provide written comments 

Overview of stewardship programs

● Mark White, Executive Director, Environmental Resources Coalition 

● Todd Barlow, Syngenta State Government Relations Manager

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Proposed topics for future discussion and data 

submissions

● Toxicology and Drinking Water Monitoring

- Selection of BMD

- Atrazine Monitoring Program (AMP)

● Ecotoxicology and AEMP

- Aquatic Level of Concern

- Atrazine Ecological Monitoring Program

- Sub-lethal Effects (amphibians, fish, reptiles)

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- Endangered Species Assessment

Toxicology and potential BMD selection

● Pulsatile LH Study with NOEL of 6.25 mg/kg/day is More Relevant for 

Calculation of the Point of Departure (POD) 

- NOEL for a functional indicator of effect on pulsatile LH release is for a functional indicator of effect on pulsatile LH release is

6.25 mg/kg/day – pubertal assay.

- NOEL for distributed dosing on the LH surge is greater than 50 

mg/kg/day.

- LE rat has a highly variable (or unstable) estrous cycle, more 

comprehensive data exist for SD and Wistar rats.

- Bolus dose is not reflective of human exposure.

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- Distributed dose has no effect at ≥ maximum tolerated dose on LH 

surge or reproductive endpoints.
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Toxicology - Studies In-progress

● Updated version of the PBPK model

● Non-human primate pharmacokinetic study

● Identification of metabolites in the non-human primate

● Validation of PBPK model 

● Metabolism of Atrazine in H295R 

● Atrazine metabolism in liver – Changes in Hepatic Phase I and Phase II 

Biotransformation Enzyme Expression and Substrate Availability 

Following Atrazine Exposure

● Additional university research on mode of action

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Additional university research on mode of action

Atrazine Monitoring Program and Characterization of Exposure

● Atrazine exposure is fully characterized. Using the existing 7-day 

monitoring data along with a conservative bias factor shows that MOEs 

for short term exposure are acceptable. 

● Currently 38 Community Water Systems Currently 38 Community Water Systems

- 4 eligible for waiving

● Daily monitoring program

- Flowing water bodies – Two years of monitoring complete 

- Static water bodies – second year finishing up

● Rural well overview report to be submitted

- Miller et al 2014 Rural well water quality and potential vulnerability

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Miller et al. 2014. Rural well water quality and potential vulnerability

in the Midwest. Groundwater Monitoring & Remediation. XX:000-000 

(plan submit to journal in 2013).
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Ecotoxicology – Aquatic Level of Concern

● Lines of Evidence Supporting a Level of Concern of 25-30 μg/L for 

60-days 

- SAP recommended calibration to the micro-/mesocosm dataset 

according to Giddings (2012) and recommended that all studies 

conducted at concentrations conducted at concentrations ≤30 μg/L be rescored and/or dropped be rescored and/or dropped

from the dataset

- The resultant 60-d LOC ranges from 25-30 μg/L

- Based on the specific-growth-rate (SGR) transformed aquatic plant 

data from single species laboratory studies EC50’s range from 24 to 

706 μg/L

- Based on 5 non-linear regression models, the HC5 from the SGRb d SSD f 36 61 t 69 46 /L

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based SSD range from 36.61 to 69.46 μg/L

● Periphyton, phytoplankton, and macrophytes recover rapidly from 

atrazine exposure individually and at the community level

● Biomonitoring of algal community dynamics in 6 Midwestern streams over the 

course of the corn growing season (April – July)

● Community sensitivity and recovery evaluation of native periphyton communities 

collected from 6 Midwestern streams over the course of the corn growing season 

Ecotoxicology – Ongoing Studies

g g

(April – July)

● Biosurvey assessment of benthic communities, and physical habitat in 6 

Midwestern streams during the summer window of the corn growing season

● Evaluation of algal sensitivity following pulsed exposure 

● Additional ecotox modelling

● Additional university studies (amphibian algal symbiosis, design/planning for lotic 

mesocosm)

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Sub-lethal Effects (amphibians, fish, reptiles)

● The Weight of Evidence manuscript on fish, 

amphibians and reptiles to be submitted to 

the EPA during the 60-day comment 

period. 

- Approach presented to 2012 SAP

Sex Ratio

pp p

- More than 200 atrazine publications

- Each study is scored for strength of 

methods, relevance of the biological 

response to survival, growth and 

reproduction. 

- 36 scored biological responses in 29 

fish 24 amphibians & 7 reptile species

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fish, 24 amphibians & 7 reptile species.

● Immune toxicity study - The University of Guelph finalizing study 

examining cortisol responses in zebrafish after atrazine, DACT, DEA, 

DIA exposure and a stress challenge (forced swimming speed). 

Ecotoxicology – Atrazine Ecological Monitoring Program

● Monitoring continues at 9 sites

● Data Extrapolation to non-monitored watersheds

o Validated models based on current atrazine monitoring data to be 

used for water exposure assessment (ie. PRZM-Hybrid, WARP, PCA, 

etc.) 

● Reports in progress

- Principle component analysis

- Assessments based on watershed characteristics

Oth it i / d li t

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- Other monitoring/modeling assessments
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Partial listing of studies being published in the peer reviewed 

literature

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● Foradori, C. D., A. D. Zimmerman, et al. (2013). "Atrazine inhibits 

pulsatile gonadotropin-releasing hormone (GnRH) release without 

altering GnRH messenger RNA or protein levels in the female rat." Biol

Reprod 88(1): 9/1-9/7.

Toxicology - Recent Publications

● Foradori, C. D., L. R. Hinds, et al. (2011). "The differential effect of 

atrazine on luteinizing hormone release in adrenalectomized adult 

female wistar rats." Biol Reprod 85(4): 684-689.

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Toxicology - Publications in progress

● Reproductive effects of atrazine – Repoductive Toxicity Studies with Atrazine 

and its Major metabolites in Rats

● Developmental effects of atrazine – Developmental Toxicity Studies with 

Atrazine and its Major Metabolites in Rats and Rabbits

● PBPK model – PBPK Model for Atrazine and its Chlorinated Metabolites 

Developed for the Rat and Scaled to Human

● Rat pharmacokinetics – Comparison of the Pharmacokinetics of Atrazine and its 

Chlorinated Metabolites After Gavage or Dietary Administration to the Female 

Sprague-Dawley Rat

● Risk assessment – PBK-based Probabilistic Risk Assessment of Exposure to 

Total Chlorotriazines in drinking water

● LE vs SD reproductive function – The Effects of Atrazine Administered by 

Gavage or in the Diet on Luteinizing Hormone Surge and Fertility of Sprague 

Dawley and Long Evans Female Rats

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and Long Evans Female Rats

● 24-month estrous cycle data – Lifetime Study of Reproductive Aging in the 

Female Sprague-Dawley Rat

● Immunotoxicity Study – Acitvation of the Hypothalamic-Pituitary-Adrenal Axis by 

High Doses of Atrazine Does Not Affect the Integrity of Immune Responses in 

Male or Female Sprague-Dawley Rats

Toxicology - Publications in progress (continued)

● LH surge – Exposure to Atrazine Suppresses the Estrogen-Induced Luteinizing 

Hormone (LH) Surge in Ovariectomized Sprague-Dawley Female Rats in a 

Time-Dependent Fashion. 

- 1, 2, 3, 4, 8, or 14 days exposure

● Corticosterone following atrazine exposure following atrazine exposure – Acute Oral Administration of Acute Oral Administration of

Atrazine Stimulates Corticosterone Release by Acting at the Level of the 

Pituitary

● Aromatase and Atrazine review paper – Evaluation of the Potential Mechanisms 

of Actions Underlying the Effect of Triazines on Aromatase Expression InVitro: 

Relevance to Man and the Environment

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Published Literature

● Andrus, JM, Brain, RA, Bollman W, Sullivan S, Winter D, Scanlan M, Waggoner 

JB , and Hosmer AJ. 2013. Biomonitoring of Select Sites in the Midwestern 

United States Coinciding with Varying Levels of Atrazine and Other 

Physicochemical Attributes. Environmental Toxicology and Chemistry In Prep 

● Prosser RS, Brain RA, Andrus JM, Hosmer AJ, Solomon KR, and Hanson ML. 

2013. Assessing temporal and spatial variation in sensitivity of field-derived 

periphyton communities to, and ability to recover from, atrazine exposure. 

Environmental Toxicology and Chemistry In Prep

● Lenwood W. Hall, LW, Killen WD, Anderson RD, Hosmer AJ, Brain RA. 2013. 

Assessment of Periphyton, Aquatic Macrophytes, Benthic Communities, and 

Physical Habitat in Midwestern United States Streams Coinciding with Varying 

Historical Concentrations of Atrazine. Environmental Monitoring and Assessment 

In Prep 

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● Prosser RS, Baxter LR, Brain RA, Solomon KR, and Hanson ML. Assessing the 

sensitivity and potential for recovery of phytoplankton and periphyton exposed to 

contaminants using pulse amplitude modulated fluorometry. Journal of 

Visualized Experiments (JoVE) Submitted 06/2013

Published Literature Cont.

● Prosser RS, Brain RA, Hosmer AJ, Solomon KR, and Hanson ML. 2013. 

Assessing the PSII sensitivity and recovery of field-collected periphyton

communities under laboratory conditions. Ecotoxicology Submitted 01/2013.

● Baxter LR, Brain RA; Prosser RS, Solomon KR, and Hanson ML. 2013. 

Sensitivity of an alga to atrazine is not enhanced by previous acute exposure. 

Environmental Pollution Accepted 06/2013.

● Bartell SM, Brain RA, Hendley P; and Nair SK. 2013. Modeling the Potential 

Effects of Atrazine on Aquatic Plant Communities in Midwestern Streams. 

Environmental Toxicology and Chemistry Accepted 06/2013

● Andrus JM, Winter D, Scanlan M, Sullivan S, Bollman W, Waggoner JB, Hosmer 

AJ, and Brain RA. 2013. Seasonal synchronicity of algal assemblages in three 

Midwestern streams exhibiting varying levels of atrazine and other chemicals 

from agricultural field inputs. Science of the Total Environment 458-460:125–

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g p

139.

● Brain, RA, Arnie, JR, Porch, JR, and Hosmer, AJ. 2012. Recovery of 

Photosynthesis and Growth Rate in Green, Blue-Green, and Diatom Algae After 

Exposure to Atrazine. Environmental Toxicology and Chemistry 31(11):2572–

2581.
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Published Literature Cont.

● Brain RA, Hosmer AJ, Desjardins D, Kendall TZ, Krueger HO, and Wall SB. 

2012. Recovery of duckweed from time-varying exposure to atrazine. 

Environmental Toxicology and Chemistry 31(5):1121–1128.

● Brain RA, Hoberg J, Hosmer AJ, and Wall SB. 2012. Influence of light intensity 

on the toxicity of atrazine to the submerged freshwater macrophyte Elodea 

Canadensis. Ecotoxicology and Environmental Safety 79:55–61.

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Published Literature

● Van Der Kraak GJ, Hosmer AJ, Hanson ML, Kloas W and Solomon KR. Effects 

of atrazine in fish, amphibians, and reptiles: An analysis based on quantitative 

weight of evidence. Critical Reviews in Toxicology. in prep

● Matsumoto J Hosmer Matsumoto J, Hosmer AJ and Van AJ and Van Der Kraak Der Kraak GJ The effects of atrazine on the GJ. The effects of atrazine on the

cortisol stress response in the zebrafish (Danio rerio) Comparative Biochemistry 

and Physiology C Comparative Pharmacology. in prep

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Atrazine Ecological Monitoring – Publications in Progress

● Miller et al., 2014. Development of an agronomic approach to define watershed 

scale chemical applications for environmental fate modeling. J. Environ. Qual. 

XX:000-000. (submit to J. in 2013).

● Miller et al 2014 A combined PRZM and monitoring approach for agricultural Miller et al., 2014. A combined PRZM and monitoring approach for agricultural

assessment modeling: PRZM-Hybrid. ES&T. XX:000-000. (submit to J. in 2013).

● Chen, W. and P. Mosquin. 2014. Impact of alternative monitoring frequencies on 

estimation of atrazine rolling average environmental concentrations. J. Environ. 

Qual. XX:000-000 (submit to J. in 2013).

● Mosquin, P. and W. Chen. 2014. Bias factors of different sampling frequency 

and its relationship with watershed characteristics. (submit to J. in 2014).

● Chen, W. and B. Munoz. 2014. Temporal trend of atrazine occurrence in raw 

t f U S it t t (1994 2012) ES&T ( b it t J i

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waters of U.S. community water systems (1994-2012). ES&T. (submit to J. in 

2014).

● Mosquin et al., 2014. Predicted daily concentrations with covariate time-series 

combining watershed model and monitoring data. (submit to J. in 2014).

Recent publications

● Mosquin et al., 2012. Estimation of upper centile concentrations using 

historical atrazine monitoring data from community water systems. J. 

Environ. Qual. 41:834-844.

● Ch W 2005 Si l th d f ti ti t ti Chen, W. 2005. Simple methods of estimating exposure concentrations 

of pesticide resulting from non-point applications in agricultural drainage 

networks. In Techniques in Aquatic Toxicology, Ostrander, G.K. ed. 

CRC Press: New York, vol. 2, pp. 357.

● Chen et al., 2002. A pesticide surface water mobility index and its 

relationship with concentrations in agricultural drainage watersheds. 

Environ. Toxicol. Chem. 21:298-308.

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