Document ID: EPA-HQ-OPP-2010-0125-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-03-09T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

                                     WASHINGTON, D.C.  20460												
						                                                                  
                                                                        
                                                   						         						
	OFFICE OF							PREVENTION, PESTICIDES AND

									                            TOXIC SUBSTANCES

MEMORANDUM

DATE:		February 19, 2010

SUBJECT:	Transmission of Bibliography for the 2010 Session of the FIFRA
Scientific Advisory Panel (SAP) Entitled “Re-Evaluation of Human
Health Effects of Atrazine:  Review of Experimental Animal and In Vitro
Studies and Drinking Water Monitoring Frequency”

FROM:	Tina E. Levine, Ph.D.

		Director

		Health Effects Division

		

TO:		Joseph Bailey

		Designated Federal Official

		FIFRA Scientific Advisory Panel

		Office of Science Coordination and Policy (7201M)

On November 3, 2009, EPA presented its review plan for a year long
re-evaluation of the human health effects of atrazine .  This review
plan involves three FIFRA Scientific Advisory Panel (SAP) meetings
planned for 2010.  In the report from the November, 2009 meeting, the
SAP requested that review materials be provided “as early as possible
in advance of each [SAP] meeting (SAP report, December 2, 2009).”  
This memo transmits the Agency’s list of references relevant for the
second SAP meeting on the human health effects of atrazine.   

The second SAP meeting will focus on a variety of important scientific
issues related to the toxicity and exposure profile of atrazine.  The
Agency will solicit comments from the Panel on issues such as potential
toxicity to the hypothalamic-pituitary-adrenal (HPA) axis, immune
system, prostate, brain, and alterations to the enzyme aromatase.  In
addition, the Agency plans to discuss the scientific issues associated
with lifestage susceptibility and linking a chemically-induced
activation of the HPA axis to other health outcomes and possible
approaches to use key events in a mode of action in risk assessment. 
The Agency will also seek feedback about monitoring water exposure and
guidance to help refine the sampling frequency for monitoring community
water systems (CWS).

      This second SAP meeting, the Agency’s scientific review of
toxicology studies will focus on both those studies used to support the
2003 reregistration of atrazine and new studies.  A review of the
scientific literature of new data on atrazine and/or its metabolites
available since the 2003 Interim Reregistration Eligibility Decision
(IRED) has been conducted.  The scope of this evaluation is restricted
to articles reporting on effects in mammals or in vitro studies from
mammalian or human cell lines that provide data on toxicity,
pharmacokinetics, and/or mode of action (MOA) of atrazine and/or its
metabolites.  The purpose of this literature review was to determine the
state-of-the-science since the 2003 atrazine IRED. To obtain peer
reviewed references on atrazine, EPA conducted searches using three
online bibliographic databases: PubMed, TOXLINE, and EMBASE.  These
searches encompassed studies on atrazine and/or its metabolites
published between the years 2003 to 2009.    Published articles excluded
from the Agency’s preliminary analysis included:    

Studies conducted on non-mammalian species;

Commentaries or letters to the editor;

Abstracts lacking sufficient detail on methods and results;

Topic reviews that did not present original work;

The Agency’s scientific review encompasses toxicology studies will
include studies available up to January 30, 2010.  Studies that become
available after that date will be integrated into the Agency’s weight
of the evidence (WOE) analysis scheduled for review by the FIFRA SAP in
September 2010.   The Agency is aware of a number of published studies
on the effects of atrazine on the development of the mammary gland.  The
Agency is also aware of several new studies expected to be published in
spring 2010 which may further characterize the effects of atrazine on
development of the mammary gland.  Thus, evaluation of all studies on
the development of the mammary gland will be deferred to the September
2010 SAP meeting where both toxicity studies and epidemiology studies
will be considered. 

EPA has evaluated approximately 100 studies for this upcoming SAP
meeting.  In addition to the studies published after the 2003 IRED,
select references published before 2003 have been included to provide
context and/or historical background.  A bibliography of these relevant
references is attached.  

Bibliography

Post 2003 References 

Albanito, L., Lappano, R., Madeo, A., Chimento, A., Prossnitz, E.R.,
Cappello, A.R., Dolce, V., Abonante, S., Pezzi, V., & Maggiolini, M.
(2008).  G-protein-coupled receptor 30 and estrogen receptor-alpha are
involved in the proliferative effects induced by atrazine in ovarian
cancer cells,  Environ Health Perspect, 116:12, 1648-1655.

Belloni V, Alleva E, et al.  (2007).  Effects of low doses of atrazine
on the neurobehavioural development of mice.  Ethology Ecology &
Evolution, 19, 309-322.  

Benachour, N., Moslemi, S., Sipahutar, H., & Seralini G.E. (2007). 
Cytotoxic effects and aromatase inhibition by xenobiotic endocrine
disrupters alone and in combination, Toxicology and Applied
Pharmacology, 222:2, 129-140.

Betancourt, M., Resendiz, A., & Fierro, E.C,	 (2006).  Effects of two
insecticides and two herbicides on the porcine sperm motility patterns
using computer-assisted semen analysis (CASA) in vitro.  Reprod Toxicol,
Oct, 22:3, 508-12.

Cimino-Reale, G., Ferrario, D., Casati, B., Brustio, R., Diodovich, C.,
Collotta, A., Vahter, M., & Gribaldo, L. (2008).  Combined in utero and
juvenile exposure of mice to arsenate and atrazine in drinking water
modulates gene expression and colonogenicity of myeloid progenitors. 
Toxicol Lett, Jul 180:1, 59-66.

Coban, A, & Filipov, N.M. (2007).  Dopaminergic toxicity associated with
oral exposure to the herbicide atrazine in juvenile male C57BL/6 mice. 
J. Neurochem, Mar, 100:5, 1177-87.

Coder, Pragati Sawhney (Syngenta) (2010).  Atrazine-An oral
developmental toxicity study of atrazine in the rat, including
cross-fostering and pair-feeding.  Unpublished data from Syngenta, 3000
pgs

Devos, S., Hooghe, R., Hooghe-Peters, E.L., De Bosscher, K., Vanden
Berghe, W., Haegeman, G., Staels, B., Bauer, E., Roels, F., & Hooghe, R.
(2003).  Inhibition of cytokine production by the herbicide atrazine:
Search for nuclear receptor targets.  Biochemical Pharmacology, 65:2,
303-308.

Devos S, Van Den Heuvel R, et al.  (2004).  Limited effect of selected
organic pollutants on cytokine production by peripheral  blood
leukocytes.  Eur. Cytokine Netw, 15, 145-151.

Dooley, G.P., Reardon, K.F., Prenni, J.E., Tjalkens, R.B., Legare, M.E.,
Foradori, C.D., Tessari, J.E., & Hanneman, W.H. (2008).  Proteomic
analysis of diaminocholorotriazine adducts in Wistar rat pituitary
glands and LbetaT2 rat pituitary cells.  Chem Res Toxicol, Apr, 21:4,
844-51.

Dooley, G., Prenni, J., Prentiss, P., Cranmer, B., Anderson, M., &
Tessari, J. (2006).  Identification of a novel hemoglobin adduct in
Sprague-Dawly rats exposed to atrazine.  Chem Res Toxicol, 19, 692-700.

Dooley, G., Hanneman, W., Carbone, D., Legare, M., Anderson, M., &
Tessari, J. (2007).  Development of an immunochemistry detection method
for atrazine-induced albumin adducts.  Chem Res Toxicol, 201, 1061-1066.

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 after acute prenatal exposure to an atrazine metabolite
mixture in female Long-Evans rats.  Environ Health Perspect, Apr, 115:4,
541-547.

Fan, W., Yanase, T., Morinaga, H., Gonda, S., Okabe, T., Nomura, M.,
Hayes, T., Takayanagi, R., & Nawata, H.(2007).  Herbicide atrazine
activates SF-1 by direct affinity and concomitant co-activators
recruitments to induce aromatase expression via promoter II. 
Biochemical and Biophysical  Research Communications, 355:4 1012-1018.

Fan, W., Yanase, T., Morinaga, H., Gondo, S., Okabe, T., Normura, M.,
Komatsu, T., Moroashi, K., Hayes, T.B., Takayanagi, R., & Nawata, H.
(2007).  Atrazine-induced aromatase expression is SF-1 dependent:
implications for endocrine disruption in wildlife and reproductive
cancers in humans.  Environ Health Perspect, May, 115:5, 720-727.

Filipov, N.M., Pinchuk, L.M., Boyd, B.L., & Crittenden P.L. (2005). 
Immunotoxic effects of short-term atrazine exposure in young male
C57BL/6 mice.  Toxicological Sciences, 86:2, 324-332.

Filipov, N.M., Stewart, M.A., Carr, R.L., & Sistrunk, S.C. (2007). 
Dopaminergic toxicity of the herbicide atrazine in rat striatal slices. 
Toxicology, 232:1-2, 68-78.

Foradori, C., Hinds, L., Hanneman, W., & Handa, R.  (2009a).  Effects of
atrazine and its withdrawal on gonadotropin-releasing hormone
neuroendocrine function in the adult female Wistar rat.  Biology of
Reproduction, Dec, 81:6, 1099-1105.

Foradori, C., Hinds, L., Hanneman, W., Legare, M., Clay, C., & Handa, R.
(2009b).  Atrazine inhibits pulsatile luteinizing hormone release
without altering pituitary sensitivity to a gonadotropin-releasing
hormone receptor agonist in female Wistar rats.  Biology of
Reproduction, 81:1, 40-45.

Foradori, C.D., Hinds, L.R., et al. (2009c).  Effects of atrazine on
GnRH neuroendocrine function after its withdrawal in the adult female
Wistar rat.  Biology of Reproduction, 81:6, 1099-1105.

Fujimoto, N. and Honda, H. (2003).  Effects of environmental estrogenic
compounds on growth of a transplanted estrogen responsive pituitary
tumor cell line in rats.  Food Chem Toxicol, Dec, 41:12, 1711-1717.

Fukamachi, K., Han, B.S., Kim, C.K., Takasuka, N., Matsuoka, Y.,
Matsuda, E., Yamasaki, T., and Tsuda, H. (2004).  Possible enhancing
effects of atrazine and nonylphenol on
7,2-dimethylbenz[a]anthracene-induced mammary tumor development in human
c-Ha-ras proto-oncogene transgenic rats.  Cancer Sci., 95:5, 404-410.

Giusi, G., Facciolo, R.M., Canoaco, M., Alleva, E., Santucci, D.,
Belloni, V., & Dessi-Fulgheri, F. (2006).  The endocrine disruptor
atrazine accounts for a dimorphic somatostatinergic neuronal expression
pattern in mice.  Toxicological Sciences, 89:1, 257-264.

Gojmerac, T., Pleadin, J., Zuric, M., Rajkovic-Janje, R., & Korsic, M.
(2004).  Serum luteinizing hormone response to administration of
gonadotropin-releasing hormone to atrazine-treated gilts.  Vet Hum
Toxicol, Oct, 6:5, 245-247.

Hase, Y., Tatsuno, M., Nishi, T., Kabe, Y., Yamaguchi, Y., Hanada, H.,
Kataoka, K., Ozawa, N., Natori, M., Handa, H., & Wantabe, H. (2008). 
Atrazine binds to F1F0-ATP synthase and inhibits mitochondrial function
in sperm.  Biochemical and Biophysical Research Communications, 366:1,
66-72.

Heneweer, M., Van den Berg, M., & Sanderson, J.T. (2004).  A comparison
of human H295R and rat R2C cell lines as in vitro screening tools for
effects on aromatase.  Toxicol. Lett., 149:2, 183-194.

Higley, E.B., Newsted, J.L., Zhang, X., Giesy, J.P., & Hecker, M.
(2010).  Assessment of chemicals effects on aromatase activity using the
H295R cell line.  Environ Sci Pollut Res Int.,  Jan, 20, Epub ahead of
print	

Hocking, B. (2009).  Melamine-contaminated powdered formula and
urolithiasis.  N Engl J Med., June, 360:25, 2676-2677.

Holloway, A.C., Anger, D.A., Crankshaw, D.J., Wu, M., & Foster, W.G.
(2008).  Atrazine-induced changes in aromatase activity in estrogen
sensitive target tissues.  J. Appl. Toxicol., Apr, 28:3, 260-270.

Hossain, M. M. & Filipov, N. M.(2008).  Alteration of dopamine uptake
into rat striatal vesicles and synaptosomes caused by an in vitro
exposure to atrazine and some of its metabolites.  Toxicology, 248,
52-58.

Juliani, C.C., Silva-Zacarin, E.C., Santos, D.C., & Boer, P.A.(2008). 
Effects of atrazine on female Wistar rats: morphological alterations in
ovarian follicles and immunocytochemical labeling of 90 kDa heat shock
protein.  Micron, Jul, 39:5, 607-616.

Kandori, H., Suzuki, S., Asamoto, M., et al. (2005).  Influence of
atrazine administration and reduction of calorie intake on prostate
carcinogenesis in probasin/SV40 T antigen transgenic rats.  Cancer Sci.,
96, 221-226.

Karrow, N.A., McCay, J.A., Brown, R.D., Musgrove, D.L., Guo, T.L.,
Germolec, D.R., & White, K.L. Jr (2005).  Oral exposure to atrazine
modulates cell-mediated immune function and decreases host resistance to
the B16F10 tumor model in female B6C3F1 mice.  Toxicology, Apr, 209:1,
15-28.

Kim, D., Breckenridge, C. (Syngenta) (2010).  Atrazine - Derivation of
the short-term inhalation NOAEL using a physiologically-based
pharmacokinetic model.  Unpublished data from Syngenta

	

Kirby E.D., Geraghty A.C., Ubuka T., Bentley G.E., Kaufer D. (2009). 
Stress increases putative gonadotropin inhibitory hormone and decreases
luteinizing hormone in male rats.  Proc Natl Acad Sci USA, 106:27,
11324-11329. 

Kmetic, I., Gaurina Srcek, V., Silvac, I., Simic, B., Kniewald, Z., &
Kniewald, J. (2008).  Atrazine exposure decreases cell proliferation in
Chinese Hamster Ovary (CHO-K1) cell line.  Bull Environ Contam Toxicol.,
Aug, 81:2, 205-209.

etič, I., Gaurina Srček, V.,  Šimiċ,b., & Kniewald, Z. (2003) 
Cytotoxicity of Herbicide Atrazine On Chinese Hamster ovary cell Line In
Monolayer.  Toxicol Lett. 144 (Suppl 1 ):S111-S112

Laville, N., Balaguer, P., Brion, F., Hinfray, N., Casellas, C.,
Porcher, J.M., & Ait-Aissa, S. (2006).  Modulation of aromatase activity
and mRNA by various selected pesticides in the human choriocarcinoma
JEG-3 cell line.  Toxicology, 228, 98-108.

Laws, S.C., Ferrell, J.M., Stoker, T.E., & Cooper, R.L. (2003). 
Pubertal development  in female Wistar rats following exposure to
propazine and atrazine biotransformation by-products,
diamino-S-chlorotriazine and hydroxyatrazine.  Toxicological Sciences
76:1, 190-200.

Laws, S.C., Hotchkiss, M., Ferrell, J., Jayaraman, S., Mills, L., Modic,
W., Tinfo, N., Fraites, M., Stoker, T., & Cooper, R. (2009). 
Chlorotriazine Herbicides and Metabolites Activate an ACTH-Dependent
Release of Corticosterone in Male Wistar Rats.  Tox. Sci. 112(1),
78–87.

Lim, S., Ahn, S.Y., Song, I.C., Chung, M.H., Jang, H.C., Park, K.S.,
Lee, K., Pak, Y.K., & Lee, H.K. (2009).  Chronic exposure to the
herbicide, atrazine, causes mitochondrial dysfunction and insulin
resistance.  PLOS One, April, 4:4, 1-11.

Malik, S.I., Terzoudi, G.I., & Pantelias, G.E. (2004).  SCE analysis in
G2 lymphocyte prematurely condensed chromosomes after exposure to
atrazine: the non-dose-dependent increase in homologous recombinational
events does not support its genotoxic mode of action.  Cytogenet and
Genome Research, 104:1-4, 315-319.

Manske, M., Beltz, L, and Dhanwada, K. (2004). Low-Level Atrazine
Exposure Decreases Cell Proliferation in Human Fibroblasts. Arch.
Environ. Contam. Toxicol., 46, 438-444.

Maravilla-Galvan, R., Fierro, R., Gonzalez-Marquez, H., Gomez-Arroyo,
S., Jimenez, I., & Betancourt, M. (2009).  Effects of atrazine and
fenoxaprop-ethyl on capacitation and the acrosomal reaction in boar
sperm.  Int. J. Toxicol., Jan-Feb, 28:1, 24-32.

McMullin T.S. (2003).  Pharmacokinetic modeling of disposition and
time-course studies with [14C]-atrazine. J. Toxicol. Environ. Health,
66:A, 941-964.

McMullin, T.S., Andersen, M.E., Hanneman, W.H., Nagahara, A., Lund,
T.D., Pak, T., & Handa, R.J. (2004).  Evidence that atrazine and
diaminochlorotriazine inhibit the estrogen/progesterone induced surge of
luteinizing hormone in female Sprague-Dawley rats without changing
estrogen receptor action.  Toxicological Sciences, Jun, 79:2, 278-286.

McMullin, T.S., Hanneman, W.H., Cranmer, B.K., Tessari, J.D., and
Andersen, M.E. (2007).  Oral absorption and oxidative metabolism of
atrazine in rats evaluated by physiologically modeling approaches. 
Toxicology, 240, 1-14.

Mizota, K. & Ueda, H. (2006).  Endocrine disrupting chemical atrazine
causes degranulation through Gq/11 protein-coupled neurosteroid receptor
in mast cells.  Toxicol Sci., Apr, 90:2, 362-368.

Mu, H., Zhang, P., & Xu, J. (2008).  Testicular toxicity and mechanisms
of chlorotoluron compounds in the mouse.  Toxicology Mechanisms and
Methods, 18:5, 399-403.

Pinchuk, L.M., Lee, S.R., & Filipov, N.M. (2007).  In vitro atrazine
exposure affects the phenotypic and functional maturation of dendritic
cells.  Toxicology and Applied Pharmacology, Sept, 223:3, 206-217.

Pogrmic, K., Fa, S., Dakic, V., Kaisarevic, S. & Kovacevic, R. (2009). 
Atrazine oral exposure of peripubertal male rats downregulates
steroidogenesis gene expression in Leydig cells.  Toxicol. Sci., 111:1,
189-197.

Pruett, S.B., Fan, R., Zheng, Q., Myers, L.P., & Hebert, P.(2003). 
Modeling and predicting immunological effects of chemical stressors:
characterization of a quantitative biomarker for immunological changes
caused by atrazine and ethanol.  Toxicol Sci., Oct, 75(2): Epub 2003 Jul
25, 343-354.

Pruett, S.B., Fan, R., Zheng, Q., & Schwab, C. (2009).  Patterns of
immunotoxicity associated with chronic as compared with acute exposures
to chemical or physical stressors and their relevance with regard to the
role of stress and with regard to immunotoxicity testing.  Toxicological
Sciences, June, 109:2, 265-275.

Rayburn, A.L., Moody, D.D., and Freeman, J.L. (2005).  Cytotoxicity of
technical grade versus formulations of atrazine and acetochlor using
mammalian cells.  Bull. Environ. Contam. Toxicol., 75, 691-698.

Rayner, J.L., Wolf, D.C., Rayner, J.L., Enoch, J.L., Enoch, R.R., &
Fenton, S.E. (2007).  Atrazine-induced reproductive tract alterations
after transplacental and/or lacational exposure in male Long-Evans rats.
 Toxicology and Applied Pharmacology, Feb, 218:3, 238-248.

Rodriguez, V.M., Thiruchelvam, M., & Cory-Slechta, D.A. (2005). 
Sustained exposure to the widely used herbicide atrazine: Altered
function and loss of neurons in brain monoamine systems.  Environmental
Health Perspectives, Jun, 113:6, 708-715.

Rooney, A.A., Matulka, R.A., & Luebke, R.W. (2003).  Developmental
atrazine exposure suppresses immune function in male, but not female
Spragus-Dawley rats.  Toxicol Sci., Dec, 76:2, 366-375.

Rosenberg, B.G., Chen, H., Folmer, J., Liu, J., Papadopoulos, V., &
Zirkin, B.R. (2008).  Gestational exposure to atrazine: effects on the
postnatal development of male offspring.  J Androl., May-June, 29:3,
304-311.

Ross, M.K., Jones, T.L., and Filipov, M.N. (2009).  Disposition of the
herbicide 2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine
(atrazine) and its major metabolites in mice: a liquid
chromatography/mass spectrometry analysis of urine, plasma, and tissue
levels.  Drug Metab. Dispos., 37:4, 776-786.

Rowe, A.M., Brundage, K.M., & Barnett, J.B. (2008).  Developmental
immunotoxicity of atrazine in rodents.  Basic and Clinical Pharmacology
and Toxicology, Feb, 102:2, 139-145.

Rowe, A.M., Brundage, K.M., & Barnett, J.B. (2007).  In vitro atrazine
exposure inhibits human natural killer cell lytic granule release. 
Toxicology and Applied Pharmacology, Jun, 221:2, 179-188.

Rowe, A.M., Brundage, K.M., Schafer, R., & Barnett, J.B. (2006). 
Immunomodulatory effects of maternal atrazine exposure on male Balb/c
mice.  Toxicology and Applied Pharmacology, 214:1, 69-77

Rusiecki, J.A., De Roos, A., Lee, W.J., Dosemci, M., Lubin J.H., Hoppin,
J.A., Blair, A., & Alavanja, M.C. (2004).  Cancer incidence among
pesticide applicators exposed to atrazine in the Agricultural Health
Study.  J Natl Cancer Inst, Sept, 96:18, 1375-1382.

Santucci, D., Belloni, V., Dess&igrave, F., & Alleva, E. (2006). 
Perinatal exposure to low dose atrazine affects neurobehavioural
development of CD-1 mice.  Reprod Toxicol, Aug, 22:2, 10.

Schwab, C L, Fan R, et al. (2005).  Modeling and predicting
stress-induced immunosuppression in mice using blood parameters. 
Toxicological Sciences, 83, 101-113.

Shibayama, H., Kotera, T., Shinoda, Y., Hanada, T., Kajhara, T., Ueda,
M., Tamura, H., Ishibashi, S., Yamashita, Y., & Ochi, S. (2009). 
Collaborative work on evaluation of ovarian toxicity. 14) Two- or
four-week repeated-dose studies and fertility study of atrazine in
female rats.  J toxicol Sci., 34,147-155.

Singh, M., Kaur, P., Sandhir, R., & Kiran, R. (2008).  Protective
effects of vitamin E against atrazine-induced genotoxicity in rats. 
Mutat Res, Jul, 654:2, 145-149.

Singh, M., Sandhir, R., & Kiran, R.(2008).  Atrazine-induced alterations
in rat erthrocyte membranes: ameliorating efect of vitamin E.  J Biochem
Mol Toxicol, Sept, 225, 363-369.

Singh, M., Sandhir, R., Kiran, R., & Kaur, P. (2008).  Protective
effects of vitamin E against atrazine-induced genotoxicity in rats
Mutation Research.  Genetic Toxicology and Environmental Mutagenesis,
654:2, 145-149.

Son, H.Y., Nishikawa, A., Okazaki, K., Lee, K., Imazawa, T., & Hirose,
M. (2003).  Lack of modifying effects of atrazine and/or tamoxifen on
thyroid carcinogenesis in rat pretreated with
N-bis(2-hydroxypropyl)nitrosamine (DHPN).  Food Chem Toxicol, Dec,
41:12, 1911-1916.

Suzawa, M. & Ingraham, H.A. (2008).  The herbicide atrazine activates
endocrine gene networks via non-steroidal NR5A nuclear receptors in fish
and mammalian cells.  PloS ONE, 3:5, 1-11.

Tanaka, T., Kohno, H., Suzuki, R., & Sugie, S. (2004).  Lack of
modifying effects of an estrogenic compound atrazine on
7,12-dimethylbenz(a)anthracene-induced ovarian carcinogenesis in rats. 
Cancer Lett, Jul, 210:2, 129-137.

Tinfo, N., & Laws, S.C. (2009).  Understanding the Effects of Atrazine
on Steroidogenesis in Wistar rats.  Society of Toxicology, Itinerary
Planner, Baltimore, MD.

		

Ueda, M., Imai, T., Takizawa, T., Onodera, H., Mitsumori, K., Matsul,
T., & Hirose, M. (2005).  Possible enhancing effects of atrazine on
growth of 7,12-dimethylbenze(a) anthracene-induced mammary tumors in
ovariectomized Sprague-Dawley rats.  Cancer Sci., Jan, 96:1, 19-25.

Victor-Costa, A.B., Carozzi Bandeira, S.M., Oliveira, A.G., Bohorquiz
Mahecha, G.A. & Oliveira, C.A. (2010).  Changes in testicular morphology
and steroiodogenesis in adult rats exposed to atrazine.  Reprod Toxicol,
Doi:10.1016/j.reprotox.2009.12.006	

Whalen M M,  Loganathan B G, et al.  (2003).  Immunomodulation of human
natural killer  cell cytotoxic function by triazine and carbamate
pesticides.  Chemico-Biological Interactions, 145, 311-319. 

Yi, K.D., Breckenridge, C.B., & Simpkins, J.W. (2010a).  Evaluation of
the potential mechanisms of action underlying the effect of triazines on
aromatase expression in vitro: relevance to man and the environment. 
Unpublished data from Syngenta

	

Yi, K.D., Breckenridge, C.B., & Simpkins, J.W. (2010b).  Cytotoxicity of
atrazine and its metabolites in vitro.  Unpublished data from Syngenta
Crop Protection, Inc.

	

Yi, K.D., Breckenridge, C.B., & Simpkins, J.W. (2010c).  Dose and time
dependent effects of atrazine and metabolites on aromatase mRNA in
multiple cell types in vitro.  Unpublished data from Syngenta

	

Yi, K.D., Perez, E.J., Breckenridge, C.B.,  & Simpkins, J.W. (2010d). 
Ex vivo assessment of the effects of atrazine or its metabolites on
phosphodiesterase activity.   Unpublished data from Syngenta

	

Zeljezic, D. & Garaj-Vrhovac, V. (2004).  Genotoxicity evaluation of
pesticide formulations containing alachlor and atrazine in multiple
mouse tissues (blood, kidney, liver, bone marrow, spleen) by comet
assay.  Neoplasma, 51:3, 198-203.

Zeljezic, D., Garaj-Vrhovac, V., & Perkovic, P. (2006).  Evaluation of
DNA damage induced by atrazine and atrazine-based herbicide in human
lymphocytes in vitro using a comet and DNA diffusion assay.  Toxicology
in Vitro, Sept, 20:6, 923-935.

Zeljeciz D, & Garaj-Vrhovac, V. (2004).  Atrazine genotoxicity
evaluation in different mouse organs by comet assay.  Periodicum
Biologorum, 106:2, 155-159.

Pre-2003 References

Cooper, R.L., Stoker, T.E., Tyrey, L., Goldman, J.M., & McElroy, W.K.
(2000).  Atrazine disrupts the hypothalamic control of pituitary-ovarian
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Water Monitoring/Modeling References

1.	Blomquist, J.D., J.M. Denis, J.L. Cowles, J.A. Hetrick, R.D. Jones,
and N.B. Birchfield. 2001. Pesticides in Selected Water-Supply
Reservoirs and Finished Drinking Water, 1999-2000: Summary of Results
from a Pilot Monitoring Program.  U.S. Geological Survey Open-File
Report 01-456.  Published in cooperation with the U.S. Environmental
Protection Agency.

2.	Brown, L.C., Berthouex, P.M.  2002.  Statistics for Environmental
Engineers.  CRC Press.

3.	Conover, W.J. 1980. Practical Nonparametric Statistics.  New York:
Wiley.

4.	Crawford, C.G. 2004. Sampling Strategies for Estimating Acute and
Chronic Exposures of Pesticides in Streams. Journal of the American
Water Resources Association (JAWRA) 40(2):485-502.

5.	Deutsch, C.V., and A.G. Journel. 1998.  GSLIB: Geostatistical
Software Library and User’s Guide. Second Edition.  Oxford University
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6.	FIFRA Scientific Advisory Panel (FIFRA SAP). 2009.  A Set of
Scientific Issues Being Considered by the Environmental Protection
Agency Regarding: The Ecological Significance of Atrazine Effects on
Primary Producers in Surface Water Streams in the Corn and Sorghum
Growing Region of the United States (Part II). SAP Minutes No. 2009-06. 
May 12 – 14, 2009 FIFRA Scientific Advisory Panel. Document available
at   HYPERLINK
"http://www.epa.gov/scipoly/sap/meetings/2009/051209meeting.html" 
http://www.epa.gov/scipoly/sap/meetings/2009/051209meeting.html  

7.	Gilliom R.J., J.E. Barbash, C.G. Crawford, P.A. Hamilton, J.D.
Martin, N. Nakagaki, L.H. Nowell, J.C. Scott, P.E. Stackelberg, G.P.
Thelin, and D.M. Wolock. 2006. The quality of our Nation’s
waters—Pesticides in the Nation’s streams and ground water,
1992–2001. U.S. Geological Survey Circular 1291, 172 p. Available at  
HYPERLINK "http://pubs.usgs.gov/circ/2005/1291/pdf/circ1291.pdf" 
http://pubs.usgs.gov/circ/2005/1291/pdf/circ1291.pdf  

8.	Lee, H.K.  2004.  Bayesian Nonparametrics via Neural Networks. 
Philadelphia: ASA/SIAM.

9.	ILSI (International Life Sciences Institute), 1999. A Framework for
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Exposure Assessments. International Life Sciences Institute Risk Science
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"http://www.ilsi.org/ResearchFoundation/Publications/Estimating%20Pestic
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de%20Concentrations.pdf  

10.	Isaaks, E.H., and R.M. Srivastava. 1989.  Applied Geostatistics. 
Oxford University Press (New York, Oxford).

11.	Larson, S.J., C.G. Crawford, and R.J. Gilliom. 2004. Development and
application of Watershed Regressions for Pesticides (WARP) for
estimating atrazine concentration distributions in streams. U.S.
Geological Survey Water-Resources Investigations Report 03–4047, 68 p.
 Available at   HYPERLINK "http://pubs.usgs.gov/wri/wri034047/" 
http://pubs.usgs.gov/wri/wri034047/  

12.	Stone, W.W.,and R.J. Gilliom. 2009. Update of watershed regressions
for pesticides (WARP) for predicting atrazine concentration in streams.
U.S. Geological Survey Open-File Report 2009–1122, 22 p. Available at 
 HYPERLINK "http://pubs.usgs.gov/of/2009/1122/" 
http://pubs.usgs.gov/of/2009/1122/  

13.	Stone, W.W., R.J. Gilliom, and C.G. Crawford. 2008. Watershed
Regressions for Pesticides (WARP) for Predicting Annual Maximum and
Maximum Moving-Average Concentrations of Atrazine in Streams. U.S.
Geological Survey Open-File Report 08-1186, 19 p. Available at  
HYPERLINK "http://pubs.usgs.gov/of/2008/1186/" 
http://pubs.usgs.gov/of/2008/1186/ 

14.	U.S. Environmental Protection Agency (USEPA). 2000. FIFRA Scientific
Advisory Panel Briefing Document for a Consultation on: Monitoring
Strategies for Pesticides in Surface Derived Drinking Water. Prepared
for June 6-9, 2000 FIFRA Scientific Advisory Panel. Document available
at   HYPERLINK
"http://www.epa.gov/scipoly/sap/meetings/2000/june/drinkingwatersurvey.p
df" 
http://www.epa.gov/scipoly/sap/meetings/2000/june/drinkingwatersurvey.pd
f  

15.	U.S. Environmental Protection Agency (USEPA). 2002. Organophosphate
Pesticides: Revised Cumulative Risk Assessment.  Current as of June 10,
2002.  Documents available through the USEPA Office of Pesticide
Programs web site at   HYPERLINK
"http://www.epa.gov/pesticides/cumulative/rra-op/" 
http://www.epa.gov/pesticides/cumulative/rra-op/ . 

16	U.S. Environmental Protection Agency (USEPA). 2007a.  Acetochlor
Registration Agreement and Monitoring Program.  Documents are available
through the Federal docket.  Docket ID: EPA-HQ-OPP-2007-0725.  Available
at   HYPERLINK
"http://www.regulations.gov/search/Regs/home.html#docketDetail?R=EPA-HQ-
OPP-2007-0725" 
http://www.regulations.gov/search/Regs/home.html#docketDetail?R=EPA-HQ-O
PP-2007-0725 

17.	U.S. Environmental Protection Agency (USEPA). 2007b.  N-methyl
Carbamate Revised Cumulative Risk Assessment.  Available through the
USEPA Office of Pesticide Programs web site at   HYPERLINK
"http://www.epa.gov/oppsrrd1/REDs/nmc_revised_cra.pdf" 
http://www.epa.gov/oppsrrd1/REDs/nmc_revised_cra.pdf  .

18.	U.S. Environmental Protection Agency (USEPA). 2007c.  Preliminary
Interpretation of the Ecological Significance of Atrazine Stream-Water
Concentrations Using a Statistically-Designed Monitoring Program. 
Prepared for the December 4 – 7, 2007 FIFRA Scientific Advisory Panel.
Document available at
http://www.epa.gov/scipoly/sap/meetings/2007/120407_mtg.htm

19.	U.S. Environmental Protection Agency (USEPA). 2009a. The Ecological
Significance of Atrazine Effects on Primary Producers in Surface Water
Streams in the Corn and Sorghum Growing Region of the United States
(Part II). Prepared for the May 12 – 15, 2009 FIFRA Scientific
Advisory Panel. Document available at   HYPERLINK
"http://www.epa.gov/scipoly/sap/meetings/2009/051209meeting.html" 
http://www.epa.gov/scipoly/sap/meetings/2009/051209meeting.html  

20.	U.S. Environmental Protection Agency (USEPA). 2009b. The Ecological
Significance of Atrazine Effects on Primary Producers in Surface Water
Streams in the Corn and Sorghum Growing Region of the United States
(Part II). Addendum to Section VI: Additional Analysis of the 40 AEEMP
Sampling Sites to Identify Additional Areas That May Exceed the LOC.
Prepared for the May 12 – 15, 2009 FIFRA Scientific Advisory Panel.
Document available at   HYPERLINK
"http://www.epa.gov/scipoly/sap/meetings/2009/051209meeting.html" 
http://www.epa.gov/scipoly/sap/meetings/2009/051209meeting.html  

21.	Whitmore, R.W., Mosquin, P.L.  Investigation of Statistical
Confidence in Upper Quantiles and “Peak” Concentrations of Currently
Available Atrazine Drinking Water Monitoring Data.  January 29, 2010. 
RTI International report Submitted to the U.S. Environmental Protection
Agency by Syngenta Crop Protection, Inc.  MRID #479728-04.

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