Page 2 of 12

I. In vitro and I

n vivo L aboratory S tudies

For th e September SAP meeting, the Agency’s scientific review of atr azine experimental toxicology studies involves the following: 1) development of the mammary gland (which was not discussed at the April SAP) and 2) r elevant literature studies published from January 30, 2010 to the present using the same search strategy as for the April SAP . Some new studies were identified from the open literature. Other new experimental toxicology data come f rom EPA’s laboratories and new studies submitted by Syngenta Crop Protection. The data from EPA’s Office of Research and Developm ent includes luteinizing hormone data following a 4

- day atrazine exposure (Cooper et al, 2010 ) and the distribution of atrazine following gestational/lactational exposures ( Kamel et al, 2010; Stoker et al, 2010 ). [Note : T he Stoker et al (2010) report is a companion document to the tissue dosimetry data contained in Kamel et al (2010) .] In total, EPA has evaluated more than 20 new experimental toxicology studies for this upcoming SAP meeting

. A list of these relevant references is attached (Attachment 1).

II. Non

- Cancer Epidemiology Studies

For the September 2010 FIFRA SAP, non

- cancer related epidemiology studies are being considered. To identify the epidemiological investigations of the association between atrazine exposure and adverse health effects (non

- cancer), PubMed/Medline, Web of Science, and Google.Scholar were queried Twenty

- one non

- cancer epidemiology studies were identified on potential non

- cancer health effects of atrazine exposure . The Agency is including 19 of these in the September SAP review; the remaining two studies are not in English and translations are not yet available. A bibliography of these 19 references is provided in Attachment 2.

III. Water Monitoring/Modeling Studies

Attachment 3 provides a list of relevant referenc es related to water monitoring/modeling. This list contains all of the previously cited references, which are still relevant, in addition to sources mentioned by the April SAP either in their remarks or in their written report. Certain articles have also been added that have general relevance to or show specific applications of topics addressed at the April Meeting. Since potential directions for next steps will be discussed at the September Meeting, citing these sources was deemed to be more important t han an exhaustive search of the literature for this current bibliography.Page 3 of 12 Attachment 1: In vitro and I n vivo Experimental Toxicology

1. Abarikwu, S., Adesiyan, A., Oyeloja, T., Oyeyemi, M., Farombi, E. (2010). Changes in Sperm Characteristics and I nduction onf Oxidative Stress in the Testis and Epididymis of Experimental Rats by a Herbicide, Atrazine. Arch Environ Contam Toxicol 58:874

- 882. DOI 10.1007/s00244

- 009

- 9371

- 2.

2. Breckenridge, C., B. (2010) Atrazine : Overview of Syngenta Crop Protection, In c. Recently Conducted and On

- Going Studies on Atrazine’s Mode of Action and Potential Mammalian Toxicity. Final Report. Unpublished data from Syngenta Crop Protection, Inc. Report Number WIL

- TK0040016. Study Completion Date July 15, 2010.

3. Casas, E., Bonil la, E., Ducolomb Y, Betancourt M. 2010. Differential effects of herbicides atrazine and fenoxaprop

- ethyl, and insecticides diazinon and malathion, on viability and maturation of porcine oocytes in vitro . Toxicology in vitro 24 (2010); 224

- 230.

4. Coder, P. ( 2010a). Atrazine: An Oral (Gavage) Study to Assess the Potential for Detecting the Estrogen

- Induced Luteinizing Hormone Surge in Female Rats. Final Report. Unpublished data from Syngenta Crop Protection, Inc. Report Number WIL

- 639062. Study Completion Date July 2, 2010.

5. Coder, P. (2010 b ). Atrazine: An Oral (Gavage) Immunotoxicity and Hormone Evaluation Study for the Effects of Atrazine on Male Rats. Final Report

. Unpublished data from Syngenta Crop Protection, Inc. Report Number WIL

6390 72 . Study Completio n Date July 13 , 2010.

6. Coder, P. (2010 c ). Atrazine: An Oral (Gavage) Study of the Effects of Atrazine on the Estrous Cycle and the Estrogen

- Induced Luteinizing Hormone Surge in Female Rats. Final Interim Report. Unpublished data from Syngenta Crop Protecti on, Inc. Report Number WIL

- 639 062 . Study Completion Date July 14

, 2010.

7. Coder, P. (2010 d ). Atrazine: An Oral Developmental Toxicity Study of Atrazine in the Rat, Including Cross

- Fostering and Pair

- Feeding. Final Report. January 28, 2010. Project Number: W IL/639025, T007794/08, 140/107. Unpublished study prepared by WIL Research Laboratories, Inc. 2827 p. MRID 47972801

.

8. Cooper, R, Buckalew, A. Fraites, M., et al. (2010). Internal Report: Evaluation of Effects of the Chlorotriazine Herbicide Atrazine on the Amplitude of the Pre

ovulatory LH Surge in the Long Evans Rat. Memorandum dated July 8, 2010 from Ralph Cooper, NHEERL /ORD to Elizabeth Mendez, HED.Page 4 of 12

9. Cooper, R, Buckalew, A. Fraites, M., et al. (2010). Internal Report: Evaluation of Effects of the Chloro triazine Herbicide Atrazine on the Amplitude of the Pre

ovulatory LH Surge in the Long Evans Rat. Memorandum dated July 8, 2010 from Ralph Cooper, NHEERL/ORD to Elizabeth Mendez, HED. Corrected Report.

10. Enoch, R.R., Stanko, J.P., Greiner, S.N., Youngblood , G.L,. Rayner, J.L., Fenton, S.E., 2007. Mammary gland development as a sensitive end point acute prenatal exposure to an atrazine metabolite mixture in female Long

- Evans rats. Environmental Health Prospective. 115(4): 541

- 547.

11. Fakhouri, W., Nunez, J . and Trail, F. (2010) Atrazine binds to the Growth Hormone Releasing Hormone Receptor and Affects Growth Hormone Gene Expression. Departments of Plant Biology and Plant Pathology, Neuroscience Program, Michigan State University, East Lansing, MI.

12. Hotchk iss, M.G., Best, D.S., Cooper, R.L., Laws, S.C. (2010). Atrazine activates and ACTH

- dependant release of corticosterone and progresterone in male Wistar rats following acute exposure. Internal Report Preparted for use of the Office of Pesticide Program, Office of Chemical Safety and Pollution Prevent, U.S., EPA, Washington, DC. Memorandum dated July 15, 2010.

13. Kamel, A., Qian, Y., Podhorniak, L. (2010). Final Report on ―Determination of Atrazine and Its Metabolites in Rat Plasma, Milk, and Tissue.‖ AC B Project B10

- 15. Memorandum dated July 13, 2010. Analytical Chemistry Branch/BEAD/OPP to Ralph Cooper, NHEERL/ORD

14. Lasserre, J

- P., Fack, F., Revets, d. et al. 2009. Effects of the Endocrine Disruptors Atrazine and PCB 153 on the Protein Expression of MCF

- 7 Human Cells. Journal of Proteome Research. 8:5485

- 5496

15. Olejnik, a. Marecik, R., Bialas, W., Cyplik, P. and Grajek, W. (2010). In Vitro Studies on Atrazine Effects on Human Intestinal Cells. Water Air Soil Pollut. DOI 10.1007/s11270

- 010

- 0394

- 0.

16. Rajkov ic, V., Matavulj, M., and Johansson, O. (2010) Combined Exposure of Peripubertal Male Rats to the Endocrin e

- Disrupting Compound Atrazine and Power

- Frequency Electromagnetic Fields Causes Degranulation of Cutaneous Mast Cells: A New Toxic Environmental Haza rd? Arch Environ Contam Toxicol. DOI 10.1007/s00244

- 010

- 9477

- 6.

17. Rayner, J.L., Enoch, R.R., and Fenton, S.E. (2005)

. Adverse effects of prenatal exposure to atrazine during a critical period of mammary gland growth

. Tox. Sci. 87(1):255

- 266.Page 5 of 12

18. Rayner, J ., Wood, C., and Fenton, S. (2003 ) Exposure Parameters Necessary for Delayed Puberty and Mammary Gland Development in Long

- Evans Rats Exposed in Utero to Atrazine. Toxicology and Applied Pharmacology 195:23

- 34.

19. Singh, M., Sandhir, R., and Kiran, R. (2010 ). Effects on antioxidant status of liver following atrazine exposure and its attenuation by vitamin E. Exp Toxicol Pathol, doi:10.1016/j.etp.2010.01.00

20. Solari, M., Paquin, J., Ducharme, P., and Boily, M. (2010). P19 Neuronal Differentiation and Retinoic Acid Metabolism as Criteria to Investigate Atrazine, Nitrite, and Nitrate Developmental Toxicity. Toxicological Sciences, 113(1), 116

- 126, doi:10.1093/toxsci/kfp243

21. Stanko, J., Enoch, R., Rayner, J ., Davis, C., Wolf, D.C., Malarkey, D.E., Fenton, S.E. (2 010) Effects of Prenatal Exposure to a Low Dose Atrazine Metabolite Mixture on Pubertal Timing and Prostate Development of Male Long Evans Rats

. In press

. Elsevier Editorial System (tm) for Reproductive Toxicology Manuscript Draft

.

22. Stoker, T., Zorilla, L., Strader, L. Et al. 2010. Internal Report:The Distribution of Atrazine in the Wistar Rat Following Gestational/Lactational Exposures. Memorandum dated July 14, 2010 from Tammy Stoker, NHEERL/ORD to Elizabeth Mendez, HED/OPP.Page 6 of 12 Attachment 2: Non

- Cancer Epidemiology

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5. Environmental atrazine exposure and c ongenital malformations in New York State: An ecologic study. (2005). Birth Defects Research Part a

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6. Farr, S., Cai, J., Savitz, D., Sandler, D., Hoppin, J., & Cooper, G. (2006). Pesticide exposure and timing of menopause: the Agricultural Health Study. Am J Epidemiol, 163 (8), 731

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. 7. Farr, S., Cooper, G., Cai, J., Savitz, D., & Sandler, D. (2004). Pesticide use and menstrual cycle characteristics among premeno pausal women in the Agricultural Health Study. Am J Epidemiol, 160 (12), 1194

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.Page 9 of 12 Attachment 3: Water Monitoring/Modeling

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— Pest icides in the Nation’s streams and ground water, 1992

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